Ivermectin for COVID-19: real-time meta analysis of 63 studies
Details
• Meta analysis using the most serious outcome reported shows 69% [54‑79%] and 86% [75‑92%] improvement for early treatment and prophylaxis, with similar result..
• There is evidence of a negative publication bias, and the probability that an ineffective treatment generated results as positive as the 63 studies is estimated to be 1 in 1 trillion.• While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 27% of ivermectin studies show zero events in the treatment arm.• Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. All practical, effective, and safe means should be used. Those denying the efficacy of treatments share responsibility for the increased risk of COVID-19 becoming endemic; and the increased mortality, morbidity, and collateral damage.• The evidence base is much larger and has much lower conflict of interest than typically used to approve drugs.• All data to reproduce this paper and sources are in the appendix. See [Bryant, Hariyanto, Kory, Lawrie, Nardelli] for other meta analyses with similar results confirming efficacy.
Clinical characteristics, treatment modalities and outcome of coronavirus disease 2019 patients treated at thisday dome isolation and treatment centre, federal capital territory Abuja, Nigeria
Details
Retrospective 300 COVID-19 patients in Nigeria treated with ivermectin, zinc, vitamin C, and azithromycin, reporting no deaths. Authors conclude that early treatment is critical.
Clinical characteristics, treatment modalities and outcome of coronavirus disease 2019 patients treated at thisday dome isolation and treatment centre, federal capital territory Abuja, Nigeria
Retrospective 300 COVID-19 patients in Nigeria treated with ivermectin, zinc, vitamin C, and azithromycin, reporting no deaths. Authors conclude that early treatment is critical.
Okogbenin et al., 9/3/2021, peer-reviewed, 13 authors.
Bayesian Hypothesis Testing and Hierarchical Modeling of Ivermectin Effectiveness
Details
Updated Bayesian analysis of a subset of ivermectin trials showing that there is strong evidence to support a causal link between ivermectin and COVID-19 severity and mortality, and that the result is robust in sensitivity analysis, inclu..
Bayesian Hypothesis Testing and Hierarchical Modeling of Ivermectin Effectiveness
Updated Bayesian analysis of a subset of ivermectin trials showing that there is strong evidence to support a causal link between ivermectin and COVID-19 severity and mortality, and that the result is robust in sensitivity analysis, including exclusion of Elgazzar et al.
Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach
DetailsIn SIlico analysis of the components of ivermectin (avermectin-B1a and avermectin-B1b), suggesting different and complementary inhibitory activity of each component, with an affinity of avermectin-B1b for viral structures, and of avermect..
Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach
In SIlico analysis of the components of ivermectin (avermectin-B1a and avermectin-B1b), suggesting different and complementary inhibitory activity of each component, with an affinity of avermectin-B1b for viral structures, and of avermectin-B1a for host structures.
González-Paz et al., 8/19/2021, peer-reviewed, 9 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Structural Deformability Induced in Proteins of Potential Interest Associated with COVID-19 by binding of Homologues present in Ivermectin: Comparative Study Based in Elastic Networks Models
DetailsIn Silico elastic network model analysis of ivermectin components (avermectin-B1a and avermectin-B1b) providing a biophysical and computational perspective of proposed multi-target activity of ivermectin for COVID-19.
Structural Deformability Induced in Proteins of Potential Interest Associated with COVID-19 by binding of Homologues present in Ivermectin: Comparative Study Based in Elastic Networks Models
In Silico elastic network model analysis of ivermectin components (avermectin-B1a and avermectin-B1b) providing a biophysical and computational perspective of proposed multi-target activity of ivermectin for COVID-19.
González-Paz et al., 8/17/2021, peer-reviewed, 9 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Summary of the Evidence for Ivermectin in COVID-19
Details
Summary of the evidence base for ivermectin and COVID-19 including in vitro and in silico studies, animal studies, pharmacologic studies, clinical observation and experience, observational controlled trials, randomized controlled trials, ..
Summary of the Evidence for Ivermectin in COVID-19
Summary of the evidence base for ivermectin and COVID-19 including in vitro and in silico studies, animal studies, pharmacologic studies, clinical observation and experience, observational controlled trials, randomized controlled trials, and epidemiological data.
Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India - a cohort study
Details
Retrospective 2017 hospitalized patients in India, showing lower mortality with ivermectin treatment in unadjusted results. No group details are provided and this result is subject to confounding by indication.
Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India - a cohort study
Retrospective 2017 hospitalized patients in India, showing lower mortality with ivermectin treatment in unadjusted results. No group details are provided and this result is subject to confounding by indication.
risk of death, 19.6% lower, RR 0.80, p = 0.12, treatment 48 of 283 (17.0%), control 311 of 1475 (21.1%), unadjusted.
Elavarasi et al., 8/12/2021, retrospective, India, South Asia, preprint, 26 authors, dosage not specified.
Self-prescribed Ivermectin use is associated with a lower rate of seroconversion in health care workers diagnosed with COVID, in a dose-dependent response
Details
Retrospective 45 healthcare workes in Brazil, showing lower creation of antibodies with multiple doses of ivermectin, which may be expected due to the antiviral activity as demonstrated in multiple studies. Authors appear unaware of these..
Self-prescribed Ivermectin use is associated with a lower rate of seroconversion in health care workers diagnosed with COVID, in a dose-dependent response
Retrospective 45 healthcare workes in Brazil, showing lower creation of antibodies with multiple doses of ivermectin, which may be expected due to the antiviral activity as demonstrated in multiple studies. Authors appear unaware of these studies, citing only earlier in vitro research, which they misinterpret to suggest that therapeutic concentrations are not reached (for details on why this is incorrect see [1]). Authors combine no dose and one dose. Clinical outcomes and timing of treatment are not provided.
Early Treatment of COVID-19 with Repurposed Therapies: The TOGETHER Adaptive Platform Trial
Details
Preliminary report from the Together Trial showing mortality RR 0.82 [0.44-1.52] and combined extended ER observation or hospitalization RR 0.91 [0.69-1.19]. The trial randomization chart suggests major problems and does not match the pro..
Early Treatment of COVID-19 with Repurposed Therapies: The TOGETHER Adaptive Platform Trial
Preliminary report from the Together Trial showing mortality RR
0.82 [0.44-1.52] and combined extended ER observation or hospitalization RR
0.91 [0.69-1.19].
The trial randomization chart suggests major problems and does
not match the protocol. Trial week 43, the first week for 3 dose ivermectin,
shows ~3x patients assigned to ivermectin vs. placebo [reddit.com].
Treatment efficacy can vary significantly over time due to overall
improvement in protocols, changes in public awareness, and changes in the
distribution of variants. Minas Gerais statistics show a period of declining
CFR shortly after the time of excess assignment to ivermectin. This
introduces confounding by time, which is common in COVID-19 studies and has
often obscured efficacy because more patients in the treatment group were
earlier in time when overall treatment protocols were significantly worse.
According to this analysis [reddit.com],
the total number of patients for the ivermectin and placebo groups do not
appear to match the totals in the presentation — reaching the number reported
for ivermectin would require including some of the patients assigned to
single dose ivermectin. Reaching the placebo number requires including
placebo patients from the much earlier ivermectin single dose period, and
from the early two week period when zero ivermectin patients were
assigned.
Treatment delay is currently unknown, however the protocol
allows very late inclusion and a companion trial reported mostly late
treatment. Overall mortality is high for 18+ outpatients. Results may be
impacted by late treatment, poor SOC, and may be specific to local variants
[Faria, Nonaka, Sabino].
Treatment was administered on an empty stomach, greatly reducing expected
tissue concentration [Guzzo] and making the effective dose about
1/5th of current clinical practice. The trial was conducted in Minas Gerais,
Brazil which had substantial community use of ivermectin [otempo.com.br],
and prior use of ivermectin is not listed in the excluson criteria.
Time from symptom onset to randomization is specified as within
7 days. However the schedule of study activities specifies treatment
administration only one day after randomization, suggesting that treatment
was delayed an additional day for all patients.
This trial uses a soft primary outcome, easily subject to bias
and event inflation in both arms (e.g., observe >6 hours independent of
indication). There is also an unusual inclusion criteria: "patients with
expected hospital stays of <= 5 days". This is similar to "patients less
likely to need treatment beyond SOC to recover", and would make it very easy
to reduce the effect seen. This is not in either of the published
protocols.
The trial took place in an area of Brazil where the Gamma
variant was prominent. Brazilian clinicians report that this variant is much
more virulent, and that significantly higher dosage and/or earlier treatment
is required, as may be expected for variants where the peak viral load is
significantly higher and/or reached earlier [Faria, Nonaka].
Trial design, analysis, and presentation, along with previous
public and private statements suggest investigator bias. Design: including
very late treatment, additional day before administration, operation in a
region with high community use, specifying administration on an empty
stomach, limiting treatment to 3 days, using soft inclusion criterion and a
soft primary outcome, easily subject to bias. Analysis: authors perform
analysis excluding events very shortly after randomization for fluvoxamine
but not ivermectin, and report viral load results for fluvoxamine but not
ivermectin. Presentation: falsely describing positive but not statistically
significant effects as "no effect, what so ever" [Amrhein, odysee.com].
Prior statements: [odysee.com].
There are two published protocols, both are called "version 1",
we refer to them as 1A (3/11/21 [drive.google.com] )
and 1B (8/5/21 [gatesopenresearch.org]. 1B
deletes subgroup analysis by treatment delay, and deletes a statement
requiring prior approval for amendments. 1B adds the statement: "we
hypothesize that younger patients will benefit more than older patients."
The trial is associated with:
MMS Holdings - a company whose mission includes helping
pharmaceutical companies get approval and designing scientific studies that
help them get approval. One of their clients is Pfizer [mmsholdings.com].
Cytel Inc. - another statistical modelling company that helps pharmaceutical
companies get approval - they work very closely with Pfizer
[cytel.com].
One of the senior investigators was Dr. Craig Rayner, President
of Integrated Drug Development at Certara - another company with a similar
mission to MMS Holdings. They state on their website that: "Since 2014, our
customers have received over 90% of new drug and biologic approvals by the
FDA." One of their clients is Pfizer [certara.com].
If you are a trial participant please contact us below. For
other issues see: [twitter.com, twitter.com (B)].
A Computational Study of Ivermectin and Doxycycline Combination Drug Against SARS-CoV-2 Infection
DetailsIn silico study showing strong binding affinity of ivermectin and doxycycline for SARS-CoV-2 main protease 3CLpro, and increased binding affinity for the combination of both.
A Computational Study of Ivermectin and Doxycycline Combination Drug Against SARS-CoV-2 Infection
In silico study showing strong binding affinity of ivermectin and doxycycline for SARS-CoV-2 main protease 3CLpro, and increased binding affinity for the combination of both.
Ivermectin: a multifaceted drug of Nobel prize-honored distinction with indicated efficacy against a new global scourge, COVID-19
Details
Review concluding that the evidence supports worldwide use of ivermectin for COVID-19, complementary to immunization. Authors note that it is likely non-epitope specific, possibly retaining efficacy with new viral strains. They note that ..
Ivermectin: a multifaceted drug of Nobel prize-honored distinction with indicated efficacy against a new global scourge, COVID-19
Review concluding that the evidence supports worldwide use of ivermectin for COVID-19, complementary to immunization. Authors note that it is likely non-epitope specific, possibly retaining efficacy with new viral strains. They note that ivermectin has been safely used with 3.7 billion doses since 1987, is well tolerated even at much greater than standard doses, and has been used without serious AEs in high-dose COVID-19 treatment studies.
Santin et al., 8/3/2021, peer-reviewed, 5 authors.
Details
This is a very biased meta analysis designed to exclude almost all studies. Authors select a small subset of studies, with a majority of results based on only 1 or 2 studies, showing positive (non-statistically significant) results for 10..
This is a very biased meta analysis designed to exclude almost
all studies. Authors select a small subset of studies, with a majority of
results based on only 1 or 2 studies, showing positive
(non-statistically significant) results for 10 of 11 primary outcomes across
a total of 13 studies.
This analysis splits up studies in order to dilute the effects
and avoid statistical significance. However, we can consider the probability
of 10 of 11 positive effects occurring due to chance for an ineffective
treatment, which is very unlikely (0.006).
The study is entirely retrospective in the current version. The
protocol is dated April 20, 2021, and the most recent study included is from
March 9, 2021. The protocol was modified after publication in order to
include a close to null result (Gonzalez et al. "patients discharged without
respiratory deterioration or death at 28 days"), so the current protocol is
dated July 28, 2021.
Authors excluded many studies by requiring results at a
specific time, for example mortality, ventilation, etc. required results at
exactly 28 days. Authors excluded all prophylaxis studies by requiring
results at exactly 14 days.
Studies comparing with other medications were excluded, however
these studies confirm efficacy of ivermectin. The only case where they could
overstate the efficacy of ivermectin is if the other medication was harmful.
There is some evidence of this for excessive dosage/very late stage use,
however that does not apply to any of the studies here.
Studies using combined treatment were excluded, even when it is
known that the other components have minimal or no effect. 3 of 4 RCTs with
combined treatment use doxycycline in addition [sciencedirect.com].
Other studies were excluded by requiring PCR confirmation.
Authors are inconsistent regarding active comparators. They
state that hydroxychloroquine “does not work”, yet excluded trials comparing
ivermectin to a drug they hold to be inactive. On the other hand, remdesivir
was an acceptable comparator, although it is considered to be effective
standard of care in some locations [osf.io].
Authors fail to recognize that Risk of Bias (RoB) domains such
as blinding are far less important for the objective outcome of
mortality.
Cochrane was reputable in the past, but is now controlled by
pharmaceutical interests. For example, see the news related to the expulsion
of founder Dr. Gøtzsche and the associated mass resignation of board members
in protest [blogs.bmj.com, bmj.com, en.x-mol.com].
For another example of bias see [ebm.bmj.com].
The BiRD group gave the following early comment: "Yesterday’s
Cochrane review surprisingly doesn’t take a pragmatic approach comparing
ivermectin versus no ivermectin, like in the majority of other existing
reviews. It uses a granular approach similar to WHO’s and the flawed Roman et
al paper, splitting studies up and thereby diluting effects. Consequently,
the uncertain conclusions add nothing to the evidence base. A further
obfuscation of the evidence on ivermectin and an example of research waste.
Funding conflicts of interests of the authors and of the journal concerned
should be examined."
Authors report funding from the German Federal Ministry of
Education and Research, which may be influenced by [gcgh.grandchallenges.org].
Bias due to funding is ignored for both analyzed studies and Cochrane. For
Cochrane funders see [cochrane.org, cochrane.org (B)].
Early multidrug treatment of SARS-CoV-2 (COVID-19) and decreased case fatality rates in Honduras
Details
Report on the nationwide implementation of multi-drug COVID-19 inpatient and outpatient treatment protocols in Honduras, showing a case fatality rate decrease from 9.33% to 2.97%. No decrease was seen in Mexico, a similar Latin American c..
Early multidrug treatment of SARS-CoV-2 (COVID-19) and decreased case fatality rates in Honduras
Report on the nationwide implementation of multi-drug COVID-19 inpatient and outpatient treatment protocols in Honduras, showing a case fatality rate decrease from 9.33% to 2.97%. No decrease was seen in Mexico, a similar Latin American country that did not introduce multi-drug treatment protocols at that time. Decreases in COVID-19 case fatality rates in Honduras were associated with both the initial publication of the protocol and a subsequent outreach program. Both inpatient and outpatient protocols include ivermectin as one component.
Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study
Details
Safety analysis of an inhaled lyophilized ivermectin formulation, showing 127-fold increase in drug solubility, and identifying safe dosage levels in rats.
Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study
Safety analysis of an inhaled lyophilized ivermectin formulation, showing 127-fold increase in drug solubility, and identifying safe dosage levels in rats.
Mansour et al., 7/23/2021, peer-reviewed, 7 authors.
FLCCC Alliance and British Ivermectin Recommendation Development Group (News)
news
Joint Statement of the FLCCC Alliance and British Ivermectin Recommendation Development Group on Retraction of Early Research on Ivermectin
Details
News release noting that ivermectin remains effective after excluding Elgazzar et al. Given the large magnitude effects and 61 studies, excluding one study with ~3% of patients does not significantly change the evidence base.
FLCCC Alliance and British Ivermectin Recommendation Development Group (News)
Joint Statement of the FLCCC Alliance and British Ivermectin Recommendation Development Group on Retraction of Early Research on Ivermectin
News release noting that ivermectin remains effective after excluding Elgazzar et al. Given the large magnitude effects and 61 studies, excluding one study with ~3% of patients does not significantly change the evidence base.
Bayesian Meta Analysis of Ivermectin Effectiveness in Treating Covid-19 Disease
Details
Bayesian analysis of a subset of ivermectin trial data concluding that there is overwhelming evidence to support a causal link between ivermectin, COVID-19 severity, and mortality.
Bayesian Meta Analysis of Ivermectin Effectiveness in Treating Covid-19 Disease
Bayesian analysis of a subset of ivermectin trial data concluding that there is overwhelming evidence to support a causal link between ivermectin, COVID-19 severity, and mortality.
Muthusamy et al., Journal of Virology & Antiviral Research (Peer Reviewed)
Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the Receptor Binding Domain of SARS-CoV-2 Spike protein
DetailsIn Silico study identifying 32 anti-parisitic compounds effectively inhibiting the RBD of the SARS-CoV-2 spike protein, with ivermectin being one of the top compounds.
Muthusamy et al., Journal of Virology & Antiviral Research (Peer Reviewed)
Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the Receptor Binding Domain of SARS-CoV-2 Spike protein
In Silico study identifying 32 anti-parisitic compounds effectively inhibiting the RBD of the SARS-CoV-2 spike protein, with ivermectin being one of the top compounds.
Muthusamy et al., 7/8/2021, peer-reviewed, 5 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Effectiveness of Ivermectin-Based Multidrug Therapy in Severe Hypoxic Ambulatory COVID-19 Patients
Details
Small study of 24 consecutive patients in serious condition (9 days post symptoms, mean SpO2 87.4) using combined treatment with ivermectin, doxycycline, zinc, vitamin D, and vitamin C, showing no mortality or hospitalization with treatme..
Effectiveness of Ivermectin-Based Multidrug Therapy in Severe Hypoxic Ambulatory COVID-19 Patients
Small study of 24 consecutive patients in serious condition (9 days post symptoms, mean SpO2 87.4) using combined treatment with ivermectin, doxycycline, zinc, vitamin D, and vitamin C, showing no mortality or hospitalization with treatment. Two patients declined treatment and both died. This study uses a synthetic control arm.
risk of death, 85.9% lower, RR 0.14, p = 0.04, continuity correction due to zero event.
risk of hospitalization, 93.3% lower, RR 0.07, p = 0.001, continuity correction due to zero event.
Hazan et al., 7/7/2021, retrospective, USA, North America, preprint, 7 authors, dosage 12mg days 1, 4, 8, this trial uses multiple treatments in the treatment arm (combined with doxycycline, zinc, vitamin D, vitamin C) - results of individual treatments may vary.
Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial
Details
RCT with 501 relatively low-risk outpatients in Argentina showing hospitalization OR 0.65 [0.32-1.31]. With only 7% hospitalization, the trial is underpowered. The trial primarily includes low-risk patients that recover quickly without tr..
Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial
RCT with 501 relatively low-risk outpatients in Argentina showing hospitalization OR 0.65 [0.32-1.31]. With only 7% hospitalization, the trial is underpowered. The trial primarily includes low-risk patients that recover quickly without treatment, leaving minimal room for improvement with treatment. 74 patients had symptoms for >= 7 days and more than 25% of patients were hospitalized within 1 day (Figure S2). Among the 7 patients requiring ventilation, authors note that the earlier requirement in the ivermectin group may be due to those patients having higher severity at baseline. However, authors know the answer to this - it is unclear why it is not reported. There were more adverse events in the placebo group than the ivermectin group, suggesting a possible issue with dispensing or non-trial medication usage.Authors pre-specify multivariate analysis but do not present it, claiming "no significant differences in the univariate analysis", however multivariate analysis could significantly change the results. Consider for example if just a few extra patients in the ivermectin group were in severe condition based on baseline SpO2. The lower mean SpO2 in the ivermectin group, and the shorter time to ventilation, are consistent with this being the case. Additionally, there are 14% more male patients in the ivermectin group.An extremely large percentage of patients (55%) were excluded based on ivermectin use in the last 7 days. However, ivermectin may retain efficacy much longer (for example antiparasitic activity may persist for months [1]). A significant number of patients may also misrepresent their prior and future usage - the population is clearly aware of ivermectin, and patients with progressing disease may be motivated to take it, predicting that they are in the control group.There were no serious adverse events. NCT04529525.
A Continuation of a Timeline of Ivermectin-Related Events in the COVID-19 Pandemic [June 30, 2021]
Details
An extension of the ivermectin timeline covering April - June 2021, including WHO's role and funding, Gavi, COVAX, Trusted News Initiative, International Fact-Checking Network, the role of private philantrophy, Frontiers, comparison to th..
A Continuation of a Timeline of Ivermectin-Related Events in the COVID-19 Pandemic [June 30, 2021]
An extension of the ivermectin timeline covering April - June 2021, including WHO's role and funding, Gavi, COVAX, Trusted News Initiative, International Fact-Checking Network, the role of private philantrophy, Frontiers, comparison to the H1N1 pandemic, new treatment protocols, and causal modeling.
Roman et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab591 (preprint 5/25/21) (Peer Reviewed) (meta analysis)
meta-analysis
Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials
Details
This is a severely flawed meta analysis. An open letter signed by 40 physicians detailing errors and flaws, and requesting retraction, can be found at [ trialsitenews.com ] . See also [ bird-group.org ] . Authors cherry-pick to include on..
Roman et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab591 (preprint 5/25/21) (Peer Reviewed) (meta analysis)
Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials
This is a severely flawed meta analysis. An open letter signed
by 40 physicians detailing errors and flaws, and requesting retraction, can
be found at [trialsitenews.com].
See also [bird-group.org].
Authors cherry-pick to include only 4 studies reporting
non-zero mortality and they initially claimed a mortality RR of 1.11
[0.16-7.65]. However, they reported incorrect values for Niaee et al.,
claiming an RR of 6.51 [2.18-19.45], when the correct RR for Niaee et al. is
0.18 [0.06-0.55]. After correction, their cherry-picked studies show >60%
mortality reduction, however authors did not correct the conclusion.
Similarly, for viral clearance and NCT04392713, they report
20/41 treatment, 18/45 control, whereas the correct day 7 clearance numbers
are 37/41 and 20/45 (sum of clearance @72hrs and @7 days), or 17/41 and
2/45 @72 hrs.
The duration of hospital stay for Niaee et al. is also
incorrectly reported, showing a lower duration for the control group.
All of the errors are in one direction - incorrectly reporting
lower than actual efficacy for ivermectin. Authors claim to include all RCTs
excluding prophylaxis, however they only include 10 of the 24 non-prophylaxis
RCTs (28 including prophylaxis at the time of publication). Authors actually
reference meta analyses that do include the missing RCTs, so they should be
aware of the missing RCTs.
The authors state that they have no conflicts of interest on
medRxiv, however Dr. Pasupuleti’s affiliation is Cello Health, whose website
[cellohealth.com] notes that they provide services such
as “brand and portfolio commercial strategy for biotech and pharma”, and that
their clients are "24 of the top 25 pharmaceutical companies”.
Only one of these errors has been partially fixed as of 5/29 -
the Niaee RR was corrected, but the associated conclusion was not. Other
errors have not been corrected. Comments on this article appear to be
censored, with zero comments posted as of July 5.
Results from ivermectin use from the Misiones Ministry of Public Health
Details
News report on ivermectin use in Misiones, Argentina, showing significantly lower hospitalization and mortality, and a dose-dependent effect with improved results for those taking 0.6mg/kg.
Results from ivermectin use from the Misiones Ministry of Public Health
News report on ivermectin use in Misiones, Argentina, showing significantly lower hospitalization and mortality, and a dose-dependent effect with improved results for those taking 0.6mg/kg.
Misiones Ministry of Public Health et al., 6/22/2021, preprint, 1 author.
Increase in Outpatient Ivermectin Dispensing in the US During the COVID-19 Pandemic: A Cross-Sectional Analysis
Details
CDC analysis of ivermectin prescriptions in the US suggesting that, while national health authority recognition is delayed in that country, many physicians are aware of the efficacy demonstrated in clinical trials.
Increase in Outpatient Ivermectin Dispensing in the US During the COVID-19 Pandemic: A Cross-Sectional Analysis
CDC analysis of ivermectin prescriptions in the US suggesting that, while national health authority recognition is delayed in that country, many physicians are aware of the efficacy demonstrated in clinical trials.
Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial
Details
Proof of concept RCT with 30 ivermectin patients and 15 control patients, showing a concentration dependent antiviral activity, but no significant difference in clinical outcomes. There was no significant difference in viral load reductio..
Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial
Proof of concept RCT with 30 ivermectin patients and 15 control patients, showing a concentration dependent antiviral activity, but no significant difference in clinical outcomes. There was no significant difference in viral load reduction between groups overall, but a significant difference was found in patients with higher median plasma ivermectin levels (72% vs. 42%, p=0.004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r=0.47, p=0.02). The change in viral load is provided for the <160ng/mL and >160ng/mL groups, but not the overall treatment group. The corrigendum provides individual viral decay rates for computing the overall treatment group viral decay rate. NCT004381884. Authors published a corrigendum: [1].
risk of mechanical ventilation, 151.9% higher, RR 2.52, p = 1.00, treatment 1 of 27 (3.7%), control 0 of 14 (0.0%), continuity correction due to zero event.
risk of disease progression, 3.7% higher, RR 1.04, p = 1.00, treatment 2 of 27 (7.4%), control 1 of 14 (7.1%).
viral decay rate, 65.6% lower, relative load 0.34, p = 0.09, treatment 20, control 14, relative mean viral decay rate (corrigendum table 2).
Krolewiecki et al., 6/18/2021, Randomized Controlled Trial, Argentina, South America, peer-reviewed, 23 authors, dosage 600μg/kg days 1-5.
Bryant et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001402 (preprint 3/11/21) (Peer Reviewed) (meta analysis)
death, ↓62.0%, p=0.005
Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines
Details
Systematic review, meta analysis, and trial sequential analysis of 24 RCTs finding mortality RR 0.38 [0.19-0.73].
Bryant et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001402 (preprint 3/11/21) (Peer Reviewed) (meta analysis)
Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines
Systematic review, meta analysis, and trial sequential analysis of 24 RCTs finding mortality RR 0.38 [0.19-0.73].
risk of death, 62.0% lower, RR 0.38, p = 0.005.
Bryant et al., 6/17/2021, peer-reviewed, 7 authors.
Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19
Details
RCT 114 patients in Egypt, 57 treated with ivermectin mucoadhesive nanosuspension intranasal spray, showing faster recovery and viral clearance with treatment. NCT04716569.
Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19
RCT 114 patients in Egypt, 57 treated with ivermectin mucoadhesive nanosuspension intranasal spray, showing faster recovery and viral clearance with treatment. NCT04716569.
relative duration of fever, 63.2% lower, relative time 0.37, p < 0.001, treatment 57, control 57.
relative duration of dyspnea, 56.4% lower, relative time 0.44, p < 0.001, treatment 57, control 57.
relative duration of anosmia, 68.8% lower, relative time 0.31, p < 0.001, treatment 57, control 57.
relative duration of cough, 64.3% lower, relative time 0.36, p < 0.001, treatment 57, control 57.
risk of no virological cure, 78.6% lower, RR 0.21, p = 0.004, treatment 3 of 57 (5.3%), control 14 of 57 (24.6%).
time to viral-, 35.7% lower, relative time 0.64, p < 0.001, treatment 57, control 57.
Aref et al., 6/15/2021, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 7 authors, dosage not specified.
Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19
Details
Analysis of the manufacturing cost of several COVID-19 medications, showing a cost of $0.55 per course of ivermectin, including excipients, formulation, tax, and profit.
Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19
Analysis of the manufacturing cost of several COVID-19 medications, showing a cost of $0.55 per course of ivermectin, including excipients, formulation, tax, and profit.
Abd-Elsalam et al., Journal of Medical Virology, doi:10.1002/jmv.27122 (Peer Reviewed)
death, ↓25.0%, p=0.70
Clinical Study Evaluating the Efficacy of Ivermectin in COVID-19 Treatment: A Randomized Controlled Study
Details
RCT 164 hospitalized patients in Egypt showing lower mortality and shorter hospitalization, but without statistical significance. There were no serious adverse effects. Authors suggest the low dosage may have resulted in lower efficacy th..
Abd-Elsalam et al., Journal of Medical Virology, doi:10.1002/jmv.27122 (Peer Reviewed)
Clinical Study Evaluating the Efficacy of Ivermectin in COVID-19 Treatment: A Randomized Controlled Study
RCT 164 hospitalized patients in Egypt showing lower mortality and shorter hospitalization, but without statistical significance. There were no serious adverse effects. Authors suggest the low dosage may have resulted in lower efficacy than other trials, and recommend increased dosage in future trials. Time from symptom onset is not specified.
risk of death, 25.0% lower, RR 0.75, p = 0.70, treatment 3 of 82 (3.7%), control 4 of 82 (4.9%), OR converted to RR, logistic regression.
risk of mechanical ventilation, no change, RR 1.00, p = 1.00, treatment 3 of 82 (3.7%), control 3 of 82 (3.7%).
hospitalization time, 19.6% lower, relative time 0.80, p = 0.09, treatment 82, control 82.
Abd-Elsalam et al., 6/2/2021, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 16 authors, dosage 12mg days 1-3.
Mondal et al., Journal of the Indian Medical Association, 119:5 (Peer Reviewed)
symp. case, ↓87.9%, p=0.006
Prevalence of COVID-19 Infection and Identification of Risk Factors among Asymptomatic Healthcare Workers: A Serosurvey Involving Multiple Hospitals in West Bengal
Details
Retrospective 1,470 healthcare workers in India, showing significantly lower risk of symptomatic COVID-19 with ivermectin prophylaxis.
Mondal et al., Journal of the Indian Medical Association, 119:5 (Peer Reviewed)
Prevalence of COVID-19 Infection and Identification of Risk Factors among Asymptomatic Healthcare Workers: A Serosurvey Involving Multiple Hospitals in West Bengal
Retrospective 1,470 healthcare workers in India, showing significantly lower risk of symptomatic COVID-19 with ivermectin prophylaxis.
risk of symptomatic case, 87.9% lower, RR 0.12, p = 0.006, treatment 128, control 1342, OR converted to RR, multivariate logistic regression, control prevalence approximated with overall prevalence.
Mondal et al., 5/31/2021, retrospective, India, South Asia, peer-reviewed, 11 authors, dosage not specified.
Mountain Valley MD Receives Successful Results From BSL-4 COVID-19 Clearance Trial on Three Variants Tested With Ivectosol™
DetailsIn Vitro and mouse study with human ACE2 cells, using solubilized ivermectin with Ivectosol™, showing antiviral effect with B.1.1.7, B.1.351, and P.1 variants of SARS-CoV-2.
The ability to inject ivermectin potentially reduces the onset ..
Mountain Valley MD Receives Successful Results From BSL-4 COVID-19 Clearance Trial on Three Variants Tested With Ivectosol™
In Vitro and mouse study with human ACE2 cells, using solubilized ivermectin with Ivectosol™, showing antiviral effect with B.1.1.7, B.1.351, and P.1 variants of SARS-CoV-2.The ability to inject ivermectin potentially reduces the onset of action from ~6 hours to ~15 minutes, with much lower variability.
Mountain Valley MD et al., 5/18/2021, preprint, 1 author.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
FLCCC Alliance Statement on the Irregular Actions of Public Health Agencies and the Widespread Disinformation Campaign Against Ivermectin
Details
Analysis of the ivermectin recommendations from WHO and others, and a call to action for all citizens, scientists, and media to counter false information. Whistleblowers can submit anonymous reports and images at the bottom of this page.
FLCCC Alliance Statement on the Irregular Actions of Public Health Agencies and the Widespread Disinformation Campaign Against Ivermectin
Analysis of the ivermectin recommendations from WHO and others, and a call to action for all citizens, scientists, and media to counter false information. Whistleblowers can submit anonymous reports and images at the bottom of this page.
Potential use of azithromycin alone and in combination with ivermectin in fighting against the symptoms of COVID-19
Details
RCT 100 outpatients in Pakistan, 50 treated with ivermectin, showing faster recovery with ivermectin. All patients received AZ, zinc, vitamin C, vitamin D, and paracetemol. Details of randomization were not provided. No mortality or hospi..
Potential use of azithromycin alone and in combination with ivermectin in fighting against the symptoms of COVID-19
RCT 100 outpatients in Pakistan, 50 treated with ivermectin, showing faster recovery with ivermectin. All patients received AZ, zinc, vitamin C, vitamin D, and paracetemol. Details of randomization were not provided. No mortality or hospitalization was reported.
risk of no recovery, 68.4% lower, RR 0.32, p = 0.005, treatment 6 of 50 (12.0%), control 19 of 50 (38.0%), 6-8 days, mid-recovery.
risk of no recovery, 27.3% lower, RR 0.73, p = 0.11, treatment 24 of 50 (48.0%), control 33 of 50 (66.0%), 3-5 days.
risk of no recovery, 75.0% lower, RR 0.25, p = 0.09, treatment 2 of 50 (4.0%), control 8 of 50 (16.0%), 9-10 days.
Faisal et al., 5/10/2021, Randomized Controlled Trial, Pakistan, South Asia, peer-reviewed, 3 authors, dosage 12mg days 1-5.
News report on In Vitro results from the research institute of Prof. Zatloukal
Details
News report on In Vitro results from the research institute of Prof. Zatloukal, showing that "ivermectin was able to reduce virus replication by a factor of 1,000 even at low concentrations".
News report on In Vitro results from the research institute of Prof. Zatloukal
News report on In Vitro results from the research institute of Prof. Zatloukal, showing that "ivermectin was able to reduce virus replication by a factor of 1,000 even at low concentrations".
Zatloukal et al., 5/5/2021, preprint, 1 author.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
A Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients
Details
Systematic review and meta analysis with 30 studies included in quantitative analysis, showing mortality OR 0.39 [0.22-0.70]. Subgroup analysis of trials with severity data showed mortality OR 0.10 [0.03-0.33] for mild/moderate cases.
A Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients
Systematic review and meta analysis with 30 studies included in quantitative analysis, showing mortality OR 0.39 [0.22-0.70]. Subgroup analysis of trials with severity data showed mortality OR 0.10 [0.03-0.33] for mild/moderate cases.
Ivermectin and the odds of hospitalization due to COVID-19: evidence from a quasi-experimental analysis based on a public intervention in Mexico City
Details
Analysis of Mexico City's use of an ivermectin-based medical kit, showing significantly lower hospitalization with use. Authors use logistic-regression models with matched observations, including adjustments for age, sex, COVID severity, ..
Ivermectin and the odds of hospitalization due to COVID-19: evidence from a quasi-experimental analysis based on a public intervention in Mexico City
Analysis of Mexico City's use of an ivermectin-based medical kit, showing significantly lower hospitalization with use. Authors use logistic-regression models with matched observations, including adjustments for age, sex, COVID severity, and comorbidities.
risk of hospitalization, 74.4% lower, RR 0.26, p < 0.001, model 7, same time period, patients receiving kit.
risk of hospitalization, 68.4% lower, RR 0.32, p < 0.001, model 1, different time periods, administrative rule.
Merino et al., 5/3/2021, retrospective quasi-randomized (patients receiving kit), population-based cohort, Mexico, North America, preprint, 7 authors, dosage 6mg bid days 1-2.
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Details
Review of ivermectin trials and epidemiological data, concluding that ivermectin is effective for prophylaxis and treatment, and should be globally and systematically deployed in the prevention and treatment of COVID-19.
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Review of ivermectin trials and epidemiological data, concluding that ivermectin is effective for prophylaxis and treatment, and should be globally and systematically deployed in the prevention and treatment of COVID-19.
Clinical Variants, Characteristics, and Outcomes Among COVID-19 Patients: A Case Series Analysis at a Tertiary Care Hospital in Karachi, Pakistan
Details
Retrospective 165 hospitalized patients in Pakistan showing unadjusted lower mortality with combined ivermectin and doxycycline treatment. Details of the ivermectin group compared to other patients are not provided, however ivermectin was..
Clinical Variants, Characteristics, and Outcomes Among COVID-19 Patients: A Case Series Analysis at a Tertiary Care Hospital in Karachi, Pakistan
Retrospective 165 hospitalized patients in Pakistan showing unadjusted lower mortality with combined ivermectin and doxycycline treatment. Details of the ivermectin group compared to other patients are not provided, however ivermectin was given to a similar percentage of patients in the mild, moderate, and severe/critical groups (34.5%, 29.1%, and 36.4%), suggesting that ivermectin treatment was not based on severity.
risk of death, 50.0% lower, RR 0.50, p = 0.03, treatment 17 of 110 (15.5%), control 17 of 55 (30.9%).
Ahsan et al., 4/29/2021, retrospective, Pakistan, South Asia, peer-reviewed, 10 authors, dosage 150μg/kg days 1-2, 150-200µg/kg, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.
Anti-inflammatory activity of ivermectin in late-stage COVID-19 may reflect activation of systemic glycine receptors
Details
Review suggesting that the effectiveness of ivermectin in the cytokine storm phase of COVID-19 may be, at least in part, an anti-inflammatory effect mediated by increased activation of glycine receptors on leukocytes and possibly vascular..
Anti-inflammatory activity of ivermectin in late-stage COVID-19 may reflect activation of systemic glycine receptors
Review suggesting that the effectiveness of ivermectin in the cytokine storm phase of COVID-19 may be, at least in part, an anti-inflammatory effect mediated by increased activation of glycine receptors on leukocytes and possibly vascular endothelium.
DiNicolantonio et al., 4/19/2021, peer-reviewed, 3 authors.
Details
Small quasi-randomized (patient choice) study with 25 PCR+ patients in a nursing home offered ivermectin, of which 10 chose to be treated. The mean age was 83.5 in the treatment group and 81.8 in the control group. There was lower mortali..
Small quasi-randomized (patient choice) study with 25 PCR+ patients in a nursing home offered ivermectin, of which 10 chose to be treated. The mean age was 83.5 in the treatment group and 81.8 in the control group. There was lower mortality and fewer serious cases with treatment.
risk of death, 70.0% lower, RR 0.30, p = 0.34, treatment 1 of 10 (10.0%), control 5 of 15 (33.3%).
risk of COVID-19 severe case, 55.0% lower, RR 0.45, p = 0.11, treatment 3 of 10 (30.0%), control 10 of 15 (66.7%).
Loue et al., 4/17/2021, retrospective quasi-randomized (patient choice), France, Europe, peer-reviewed, 2 authors, dosage 200μg/kg single dose.
Ivermectin as a SARS-CoV-2 Pre-Exposure Prophylaxis Method in Healthcare Workers: A Propensity Score-Matched Retrospective Cohort Study
Details
Propensity matched retrospective prophylaxis study of healthcare workers in the Dominican Republic showing significantly lower cases with treatment, and no hospitalization with treatment (versus 2 in the PSM matched control group). The ca..
Ivermectin as a SARS-CoV-2 Pre-Exposure Prophylaxis Method in Healthcare Workers: A Propensity Score-Matched Retrospective Cohort Study
Propensity matched retrospective prophylaxis study of healthcare workers in the Dominican Republic showing significantly lower cases with treatment, and no hospitalization with treatment (versus 2 in the PSM matched control group). The cases with treatment were mostly in the first week, with only one case in the second and third weeks, and none in the fourth week. There were no severe side effects. In post-hoc analysis, as the treatment group discontinued treatment over time, their protection also decreased. NCT04832945.
risk of hospitalization, 80.0% lower, RR 0.20, p = 0.50, treatment 0 of 271 (0.0%), control 2 of 271 (0.7%), continuity correction due to zero event, PSM.
risk of COVID-19 case, 74.0% lower, RR 0.26, p = 0.008, treatment 5 of 271 (1.8%), control 18 of 271 (6.6%), adjusted, PSM, multivariate Cox regression.
Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
Details
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin ..
Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C.The ivermectin dosage was low for 42 days prophylaxis - only a single dose of 200µg/kg, with a maximum of 12mg.Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters.There were no hospitalizations and no deaths. NCT04446104.
risk of symptomatic case, 49.8% lower, RR 0.50, p = 0.01, treatment 32 of 617 (5.2%), control 64 of 619 (10.3%).
risk of COVID-19 case, 5.8% lower, RR 0.94, p = 0.61, treatment 398 of 617 (64.5%), control 433 of 619 (70.0%), adjusted, OR converted to RR, model 6.
Seet et al., 4/14/2021, Cluster Randomized Controlled Trial, Singapore, Asia, peer-reviewed, 15 authors, dosage 12mg single dose, 200µg/kg, maximum 12mg, this trial compares with another treatment - results may be better when compared to placebo.
Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARS-CoV-2 targets
DetailsIn Silico analysis finding that the in vitro activity of ivermectin may explained by acting as an inhibitor of importin-α, dimeric 3CLpro, and Nsp9.
A timeline of ivermectin-related events in the COVID-19 pandemic
Details
An extensive timeline of ivermectin-related events from April 2020 to March 2021 including studies, news, health authority decisions, biased news coverage, and censorship.
The author concludes that in a broader historical perspective, th..
A timeline of ivermectin-related events in the COVID-19 pandemic
An extensive timeline of ivermectin-related events from April 2020 to March 2021 including studies, news, health authority decisions, biased news coverage, and censorship.The author concludes that in a broader historical perspective, the timeline depicts rather dysfunctional societies unable to properly communicate and organize themselves, leading to misallocation of resources and decisions that may have conflicted with elementary ethical considerations, with this behavior rationalized by claiming adherence to mental paradigms that may have poorly matched the situation.
Mourya et al., Int. J. Health and Clinical Research (Peer Reviewed)
viral+, ↓89.4%, p<0.0001
Comparative Analytical Study of Two Different Drug Regimens in Treatment of Covid 19 Positive Patients in Index Medical College Hospital and Research Center, Indore, India
Details
Retrospective 100 patients in India with 50 treated with ivermectin, and SOC for all patients including HCQ+AZ, showing much higher viral clearance with ivermectin. Baseline clinical status was worse in the control group. Time of testing ..
Mourya et al., Int. J. Health and Clinical Research (Peer Reviewed)
Comparative Analytical Study of Two Different Drug Regimens in Treatment of Covid 19 Positive Patients in Index Medical College Hospital and Research Center, Indore, India
Retrospective 100 patients in India with 50 treated with ivermectin, and SOC for all patients including HCQ+AZ, showing much higher viral clearance with ivermectin. Baseline clinical status was worse in the control group. Time of testing after treatment initiation was longer in the control group (mean 7.24 days versus 5.22 days).
risk of no virological cure, 89.4% lower, RR 0.11, p < 0.001, treatment 5 of 50 (10.0%), control 47 of 50 (94.0%).
Mourya et al., 4/1/2021, retrospective, India, South Asia, peer-reviewed, 5 authors, dosage 12mg days 1-7.
Cluster Randomised Trials - Ivermectin Repurposing For COVID-19 Treatment Of Outpatients With Mild Disease In Primary Health Care Centers
Details
Cluster RCT outpatients in Argentina showing signficantly faster recovery with ivermectin. There were no deaths. Cluster RCT where outpatients in Tucumán were assigned to the ivermectin group and outpatients from San Miguel de Tucumán and..
Cluster Randomised Trials - Ivermectin Repurposing For COVID-19 Treatment Of Outpatients With Mild Disease In Primary Health Care Centers
Cluster RCT outpatients in Argentina showing signficantly faster recovery with ivermectin. There were no deaths. Cluster RCT where outpatients in Tucumán were assigned to the ivermectin group and outpatients from San Miguel de Tucumán and Gran San Miguel de Tucumán were assigned to the control group. All comorbidities, percentage of male patients, and age were higher in the ivermectin group, favoring the control group. NCT04784481.
risk of no discharge, 86.9% lower, RR 0.13, p = 0.004, treatment 2 of 110 (1.8%), control 20 of 144 (13.9%), adjusted, OR converted to RR, logistic regression.
Chahla et al., 3/30/2021, Cluster Randomized Controlled Trial, Argentina, South America, preprint, 9 authors, dosage 24mg days 1, 8, 15, 22.
The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis
Details
Small meta analysis of 6 RCTs showing mortality OR 0.21 [0.11-0.42]. Authors do not include two more recent RCTs with mortality results, 10 other studies with mortality results, and a total of 42 other studies including other outcomes. Au..
The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis
Small meta analysis of 6 RCTs showing mortality OR 0.21 [0.11-0.42]. Authors do not include two more recent RCTs with mortality results, 10 other studies with mortality results, and a total of 42 other studies including other outcomes. Authors do not distinguish between studies with very different treatment delays (earlier treatment is more successful).
Why COVID-19 is not so spread in Africa: How does Ivermectin affect it?
Details
Retrospective study of the 31 onchocerciasis-endemic countries using the community-directed treatment with ivermectin (CDTI) and the 22 non-endemic countries in Africa, showing significantly lower mortality per capita in the countries us..
Why COVID-19 is not so spread in Africa: How does Ivermectin affect it?
Retrospective study of the 31 onchocerciasis-endemic countries using the community-directed treatment with ivermectin (CDTI) and the 22 non-endemic countries in Africa, showing significantly lower mortality per capita in the countries using ivermectin.
risk of death, 88.2% lower, RR 0.12, p = 0.002, relative mean mortality per million.
Tanioka et al., 3/26/2021, retrospective, ecological study, multiple countries, multiple regions, preprint, 3 authors, dosage 200μg/kg, dose varied, typically 150-200μg/kg.
Udofia et al., Network Modeling Analysis in Health Informatics and Bioinformatics, doi:10.1007/s13721-021-00299-2 (Peer Reviewed)
In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV
DetailsIn Silico analysis finding that ivermectin had the highest binding energy against the 3CLpro of SARS-CoV-2 and RdRps of both SARS-CoV and SARS-CoV-2.
Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach
DetailsIn Silico analysis finding that ivermectin has high binding affinity for the SARS-CoV-2 viral spike protein, main protease, replicase, and human TMPRSS2 receptors.
Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach
In Silico analysis finding that ivermectin has high binding affinity for the SARS-CoV-2 viral spike protein, main protease, replicase, and human TMPRSS2 receptors.
Choudhury et al., 3/25/2021, peer-reviewed, 7 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Details
Phase 2 results from a multicenter RCT of hospitalized patients in Bulgaria showing faster viral clearance, greater clinical improvement, and improved biomarkers with treatment. Ivermectin was taken on an empty stomach, potentially reduci..
Phase 2 results from a multicenter RCT of hospitalized patients in Bulgaria showing faster viral clearance, greater clinical improvement, and improved biomarkers with treatment. Ivermectin was taken on an empty stomach, potentially reducing lung tissue concentration by ~2.5x [1]. Limited data has been reported currently. No serious adverse events were observed. EudraCT 2020-002091-12.
risk of no improvement, 31.6% lower, RR 0.68, p = 0.28, treatment 13 of 50 (26.0%), control 19 of 50 (38.0%), day 7, patients with improvement on WHO scale.
risk of no improvement, 34.5% lower, RR 0.66, p = 0.07, treatment 19 of 50 (38.0%), control 29 of 50 (58.0%), day 4, patients with improvement on WHO scale.
Huvemek et al., 3/25/2021, Double Blind Randomized Controlled Trial, Bulgaria, Europe, preprint, 1 author, dosage 400μg/kg days 1-3.
Yagisawa et al., The Japanese Journal of Antibiotics, 74-1, Mar 2021 (Review) (Peer Reviewed)
review
Global trends in clinical studies of ivermectin in COVID-19
Details
Review of ivermectin for COVID-19. Authors note that Kitasato University's project was expanded in response to the results of Caly et al. which had left questions regarding in vivo therapeutic levels, and the results of those studies were..
Yagisawa et al., The Japanese Journal of Antibiotics, 74-1, Mar 2021 (Review) (Peer Reviewed)
Global trends in clinical studies of ivermectin in COVID-19
Review of ivermectin for COVID-19. Authors note that Kitasato University's project was expanded in response to the results of Caly et al. which had left questions regarding in vivo therapeutic levels, and the results of those studies were positive. Early in the pandemic, Kitasato University requested Merck to conduct clinical trials in Japan because they have priority for an expansion of ivermectin's indications, however Merck declined.Since large companies have declined to study ivermectin for COVID-19, trials have been mostly doctor-initiated with relatively little funding. Authors discuss these, noting that the physicians involved are enthusiastic about avoiding bias, and strive to treat and prevent COVID-19 witn non-profit motives.Authors discuss the trials, epidemiological data, and inaccurate statements made by certain authorities.Authors note that regulations make it challenging for doctor-initiated trials to enroll many participants in a timely manner.Authors conclude that ivermectin may turn out to be comparable to the benefits achieved from the discovery of penicillin - said to be one of the greatest discoveries of the twentieth century.Authors include the nobel prize winning biochemist who discovered ivermectin, Satoshi Ōmura [1].
Comparisons between the Neighboring States of Amazonas and Pará in Brazil in the Second Wave of COVID-19 Outbreak and a Possible Role of Early Ambulatory Treatment
Details
Comparison between the two largest neighboring states in Brazil, Amazonas and Pará, showing more than 5 times lower mortality in Pará during the second wave when the Pará government supported early treatment and Amazonas did not, compared..
Comparisons between the Neighboring States of Amazonas and Pará in Brazil in the Second Wave of COVID-19 Outbreak and a Possible Role of Early Ambulatory Treatment
Comparison between the two largest neighboring states in Brazil, Amazonas and Pará, showing more than 5 times lower mortality in Pará during the second wave when the Pará government supported early treatment and Amazonas did not, compared to similar results in the first wave when treatment protocols were similar.
Del Franco et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1008 (Peer Reviewed)
Ivermectin in Long-Covid Patients: A Retrospective Study
Details
Retrospective 856 patients previously admitted to hospital for COVID-19 in Argentina, finding that ivermectin improved recovery from "long covid" symptoms.
Del Franco et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1008 (Peer Reviewed)
Ivermectin in Long-Covid Patients: A Retrospective Study
Retrospective 856 patients previously admitted to hospital for COVID-19 in Argentina, finding that ivermectin improved recovery from "long covid" symptoms.
Del Franco et al., 3/18/2021, peer-reviewed, 3 authors.
Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study
Details
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and ..
Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups. Subject to the usual limitation of a database study, very small size, and limited evaluation of patients.
relative time to clinical response of wellbeing, 5.6% lower, relative time 0.94, p = 0.87, treatment 14, control 15.
Roy et al., 3/12/2021, retrospective, database analysis, India, South Asia, preprint, 5 authors, dosage not specified, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.
Crying wolf in time of Corona: the strange case of ivermectin and hydroxychloroquine. Is the fear of failure withholding potential life-saving treatment from clinical use?
Details
Meta analysis of RCT mortality results showing RR 0.19, p < 0.00001.
Crying wolf in time of Corona: the strange case of ivermectin and hydroxychloroquine. Is the fear of failure withholding potential life-saving treatment from clinical use?
Meta analysis of RCT mortality results showing RR 0.19, p < 0.00001.
risk of death, 79.5% lower, RR 0.21, p < 0.001, treatment 14 of 703 (2.0%), control 57 of 620 (9.2%), OR converted to RR.
Nardelli et al., 3/11/2021, peer-reviewed, 8 authors.
Scheim et al., OSF Preprints (Preprint) (meta analysis)
meta-analysis
Ivermectin sales in Valle del Cauca, Colombia, patterns of AEs, and other background re López-Medina et al. 2021
Details
Analysis of several issues with López-Medina et al. including the atypical adverse effects in the control arm and population use of ivermectin.
Scheim et al., OSF Preprints (Preprint) (meta analysis)
meta-analysis
Protocol violations in López-Medina et al.: 38 switched ivermectin (IVM) and placebo doses, failure of blinding, widespread IVM sales OTC in Cali, and nearly identical AEs for the IVM and control groups
Details
Report on protocol violations in López-Medina et al.
Scheim et al., OSF Preprints (Preprint) (meta analysis)
Protocol violations in López-Medina et al.: 38 switched ivermectin (IVM) and placebo doses, failure of blinding, widespread IVM sales OTC in Cali, and nearly identical AEs for the IVM and control groups
Report on protocol violations in López-Medina et al.
Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing
Details
Modeling study analyzing timing and dosing regimens of hydroxychloroquine, lopinavir/ritonavir, ivermectin, artemisinin, and nitazoxanide. The greatest benefits were seen when treatments were given immediately at the time of diagnosis. Au..
Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing
Modeling study analyzing timing and dosing regimens of hydroxychloroquine, lopinavir/ritonavir, ivermectin, artemisinin, and nitazoxanide. The greatest benefits were seen when treatments were given immediately at the time of diagnosis. Authors state that "For IVM, no results of clinical trials regarding its effectiveness in COVID-19 have been published yet", which is inaccurate - there were 19 peer-reviewed trials published as of Mar 10, 2021 (43 including preprints).
Kern et al., 3/10/2021, peer-reviewed, 4 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro
DetailsIn Vitro study showing that ivermectin can inhibit infection of bovine respiratory disease viral agents BCoV, BPIV-3, BVDV, BRSV and BoHV-1 at the concentrations of 2.5 and 5 μM and in a dose-dependent manner.
Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro
In Vitro study showing that ivermectin can inhibit infection of bovine respiratory disease viral agents BCoV, BPIV-3, BVDV, BRSV and BoHV-1 at the concentrations of 2.5 and 5 μM and in a dose-dependent manner.
Yesilbag et al., 3/10/2021, peer-reviewed, 3 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Use of ivermectin in the treatment of Covid-19: a pilot trial
Details
Very small RCT with 4 control patients and 28 ivermectin patients split across 3 different dosage levels, showing lower (non-statistically significant) ICU admission with treatment. Authors suggest that ivermectin for SARS-CoV-2 is safe a..
Use of ivermectin in the treatment of Covid-19: a pilot trial
Very small RCT with 4 control patients and 28 ivermectin patients split across 3 different dosage levels, showing lower (non-statistically significant) ICU admission with treatment. Authors suggest that ivermectin for SARS-CoV-2 is safe and reduces symptoms and viral load, and that the antiviral effect appears to be dose-dependent. NCT04431466.
risk of mechanical ventilation, 85.2% lower, RR 0.15, p = 0.25, treatment 1 of 27 (3.7%), control 1 of 4 (25.0%).
risk of ICU admission, 85.2% lower, RR 0.15, p = 0.25, treatment 1 of 27 (3.7%), control 1 of 4 (25.0%).
relative improvement in Ct value, 0.8% lower, RR 0.99, p = 1.00, treatment 27, control 3.
risk of no virological cure, 11.1% higher, RR 1.11, p = 1.00, treatment 10 of 27 (37.0%), control 1 of 3 (33.3%).
time to viral-, 16.7% lower, relative time 0.83, treatment 27, control 3.
Pott-Junior et al., 3/9/2021, Randomized Controlled Trial, Brazil, South America, peer-reviewed, 10 authors, dosage 200μg/kg single dose, dose varies in three arms 100, 200, 400μg/kg.
Ivermectin for COVID-19 in Peru: 14-fold reduction in nationwide excess deaths, p=.002 for effect by state, then 13-fold increase after ivermectin use restricted
Details
Analysis of ivermectin use in Peru concluding that ivermectin most likely caused a 14 times reduction in excess deaths in Peru, prior to a 13 times increase after reversal of ivermectin use. Authors conclude that the results strongly sugg..
Ivermectin for COVID-19 in Peru: 14-fold reduction in nationwide excess deaths, p=.002 for effect by state, then 13-fold increase after ivermectin use restricted
Analysis of ivermectin use in Peru concluding that ivermectin most likely caused a 14 times reduction in excess deaths in Peru, prior to a 13 times increase after reversal of ivermectin use. Authors conclude that the results strongly suggest that ivermectin can complement vaccination. They note that the potential mechanism of action, competitive binding with the SARS-CoV-2 spike protein, is likely to be non-epitope specific, possibly maintaining efficacy against emerging mutant strains.
Chamie-Quintero et al., 3/8/2021, preprint, 3 authors.
Factors associated with increased mortality in critically ill COVID-19 patients in a Mexican public hospital: the other faces of health system oversaturation
Details
Retrospective 196 critically ill patients in Mexico. Patients overlap with the existing RCT by Beltran-Gonzalez (NCT04391127). This preprint shows a larger treated population and greater (non-statistically significant) improvement with iv..
Factors associated with increased mortality in critically ill COVID-19 patients in a Mexican public hospital: the other faces of health system oversaturation
Retrospective 196 critically ill patients in Mexico. Patients overlap with the existing RCT by Beltran-Gonzalez (NCT04391127). This preprint shows a larger treated population and greater (non-statistically significant) improvement with ivermectin, RR 0.81 [0.53-1.24].
Guzman et al., 3/8/2021, retrospective, Mexico, North America, preprint, 11 authors.
Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection
Details
RCT 168 very late stage severe condition hospitalized patients comparing CQ, HCQ, and ivermectin not showing significant differences. Authors were unable to add a control arm due to ethical issues.
Authors claim that "the mortality ..
Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection
RCT 168 very late stage severe condition hospitalized patients comparing CQ, HCQ, and ivermectin not showing significant differences. Authors were unable to add a control arm due to ethical issues.Authors claim that "the mortality rates of the three groups are very similar to historical reports of other studies that used placebo in hospitalized patients", without providing any reference. However [1] shows 43% hospital mortality in the northern region of Brazil, where the study was performed, from which we can estimate the mortality with ivermectin in this study is 47% lower, RR 0.53. Further, the study is restricted to more severe cases, hence the expected mortality may be higher.
Details
Safety analysis of >350 articles showing that ivermectin has an excellent safety profile. The author notes that "no severe adverse event has been reported in dozens of completed or ongoing studies involving thousands of participants..
Safety analysis of >350 articles showing that ivermectin has an excellent safety profile. The author notes that "no severe adverse event has been reported in dozens of completed or ongoing studies involving thousands of participants worldwide to evaluate the efficacy of ivermectin against COVID-19".
Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial
Details
An open letter, signed by >100 physicians, concluding this study is fatally flawed can be found at [ jamaletter.com ] . This is a phone survey based RCT with low risk patients, 200 ivermectin and 198 control, showing lower mortality, lowe..
Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial
An open letter, signed by >100 physicians, concluding this
study is fatally flawed can be found at [jamaletter.com].
This is a phone survey based RCT with low risk patients, 200
ivermectin and 198 control, showing lower mortality, lower disease
progression, lower treatment escalation, and faster resolution of symptoms
with treatment, without reaching statistical significance. Authors find the
results of this trial alone do not support the use of ivermectin. However the
effects are all positive, especially for serious outcomes which are unable to
reach statistical significance with the very small number of events in the
low risk population.
With the low risk patient population, there is little room for
improvement with an effective treatment - 59/57% (IVM/control) recovered
within the first 2 days to either "no symptoms" or "not hospitalized and no
limitation of activities"; 73/69% within 5 days. Less than 3% of all patients
ever deteriorated.
The primary outcome was changed mid-trial, it was originally
clinical deterioration, which is more meaningful, and shows greater benefit.
The new outcome of resolution of symptoms includes "not hospitalized and no
limitation of activities" as a negative outcome and is not very meaningful in
terms of assessing how much treatment reduces serious outcomes. Using this
measure could completely invalidate results - for example a treatment that
eliminates all COVID-19 symptoms but has a temporary minor adverse event
could be seen as worse.
Authors state that "preliminary reports of other randomized
trials of ivermectin as treatment for COVID-19 with positive results have not
yet been published in peer-reviewed journals", however there were 8
peer-reviewed RCTs with positive effects published prior to this paper(and 19
total peer-reviewed studies with positive effects).
Authors advised taking ivermectin on an empty stomach, reducing
lung tissue concentration by ~2.5x [Guzzo].
76 patients were excluded due to control patients receiving
ivermectin. However, there was a similar percentage of adverse events like
diarrhea, nausea, and abdominal pain in both treatment and control groups.
These are potential non-serious side effects of treatment and suggest that it
is possible that many more control patients received some kind of
treatment.
Ivermectin was widely used in the population and available OTC
at the time of the study. The study protocol only excluded patients with
previous ivermectin use within 5 days, however other trials often monitor
effects 10+ days after the last dose [osf.io].
This study reportedly has an ethical issue whereby participants
were told the study drug was "D11AX22"
https://trialsitenews.com/jama-ivermectin-study-deceived-participants-on-study-drug/.
The editor-in-chief of JAMA initially offered to help with this issue, but
later indicated that "JAMA does not review consent forms", however the lead
author reportedly confirmed the issue [francesoir.fr, trialsitenews.com, trialsitenews.com (B)].
The study protocol specifically allows "the use of other
treatments outside of clinical trials". The paper provides no information on
what other treatments were used, but other treatments were commonly used at
the time. Additionally, the control group did about 5x better than
anticipated for deterioration, also suggesting that the control patients used
some kind of treatment. Patients that enroll in such a study may be more
likely to learn about and use other treatments, especially since they do not
know if they are receiving the study medication.
The study protocol was amended 4 times. Amendments 2-4 are
provided but amendment 1 is missing. Amendment 2 increased the inclusion
criteria to within 7 days of onset, including more later stage patients and
reducing the expected effectiveness. The trial protocol lists “the duration
of supplemental oxygen” as an outcome but the results for this outcome are
missing.
Grants and/or personal fees, including in some cases during the
conduct of the study, were provided by Sanofi Pasteur, GlaxoSmithKline,
Janssen, Merck, and Gilead. For more details see [trialsitenews.com (C)].
For other confounding issues see [osf.io (B)] and additional
issues can be found in the comments of the article [jamanetwork.com].
Most data was collected via surveys, without physical
examination. 87% medication adherence. NCT04405843.
risk of death, 66.8% lower, RR 0.33, p = 0.50, treatment 0 of 200 (0.0%), control 1 of 198 (0.5%), continuity correction due to zero event.
risk of escalation of care, 60.8% lower, RR 0.39, p = 0.10, treatment 4 of 200 (2.0%), control 10 of 198 (5.1%), OR converted to RR.
risk of escalation of care with post-hoc <12h exclusion, 34.3% lower, RR 0.66, p = 0.51, treatment 4 of 200 (2.0%), control 6 of 198 (3.0%), OR converted to RR.
risk of deterioration by >= 2 points on an 8-point scale, 43.1% lower, RR 0.57, p = 0.35, treatment 4 of 200 (2.0%), control 7 of 198 (3.5%), OR converted to RR.
risk of fever post randomization, 24.8% lower, RR 0.75, p = 0.33, treatment 16 of 200 (8.0%), control 21 of 198 (10.6%), OR converted to RR.
risk of unresolved symptoms at day 21, 15.3% lower, RR 0.85, p = 0.53, treatment 36 of 200 (18.0%), control 42 of 198 (21.2%), OR converted to RR, Cox proportional-hazard model.
hazard ratio for lack of resolution of symptoms, 6.5% lower, RR 0.93, p = 0.53, treatment 200, control 198.
relative median time to resolution of symptoms, 16.7% lower, relative time 0.83, treatment 200, control 198.
López-Medina et al., 3/4/2021, Double Blind Randomized Controlled Trial, Colombia, South America, peer-reviewed, median age 37.0, 19 authors, dosage 300μg/kg days 1-5.
The Binding mechanism of ivermectin and levosalbutamol with spike protein of SARS-CoV-2
DetailsIn SIlico analysis predicting that ivermectin has a large binding affinity for the SARS-CoV-2 spike protein. Three different computer modeling techniques show that ivermectin can inhibit SARS-CoV-2 entrance via hACE2.
The Binding mechanism of ivermectin and levosalbutamol with spike protein of SARS-CoV-2
In SIlico analysis predicting that ivermectin has a large binding affinity for the SARS-CoV-2 spike protein. Three different computer modeling techniques show that ivermectin can inhibit SARS-CoV-2 entrance via hACE2.
Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial
Details
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 36 low dose ivermectin and 37 control patients not finding significant differences. NCT04391127. Questions have been rais..
Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high
comorbidity hospitalized patients in Mexico with 36 low dose ivermectin and
37 control patients not finding significant differences. NCT04391127.
Questions have been raised about this study and the early
termination of the study and discontinuation of treatments, because the
hospital statistics show a dramatically lower (~75%) case fatality rate
during the period of the study [twitter.com] (data from [gob.mx]).
risk of death, 14.4% lower, RR 0.86, p = 1.00, treatment 5 of 36 (13.9%), control 6 of 37 (16.2%).
risk of respiratory deterioration or death, 8.6% lower, RR 0.91, p = 1.00, treatment 8 of 36 (22.2%), control 9 of 37 (24.3%).
risk of no hospital discharge, 37.0% higher, RR 1.37, p = 0.71, treatment 4 of 36 (11.1%), control 3 of 37 (8.1%).
hospitalization time, 20.0% higher, relative time 1.20, p = 0.43, treatment 36, control 37.
Gonzalez et al., 2/23/2021, Double Blind Randomized Controlled Trial, Mexico, North America, preprint, mean age 53.8, 13 authors, dosage 12mg single dose, 18mg for patients >80kg.
Details
The British Ivermectin Recommendation Development (BIRD) panel, with dozens of multi-national scientists & doctors, issued sweeping recommendations for the immediate global use of ivermectin.
The British Ivermectin Recommendation Development (BIRD) panel, with dozens of multi-national scientists & doctors, issued sweeping recommendations for the immediate global use of ivermectin.
Effect of a combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-1
Details
Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.
Effect of a combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-1
Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.
risk of no virological cure, 86.9% lower, RR 0.13, p < 0.001, treatment 7 of 62 (11.3%), control 44 of 51 (86.3%), day 15.
risk of no virological cure, 58.1% lower, RR 0.42, p < 0.001, treatment 26 of 62 (41.9%), control 51 of 51 (100.0%), day 7.
Elalfy et al., 2/16/2021, retrospective, Egypt, Africa, peer-reviewed, 15 authors, dosage 18mg days 1, 4, 7, 10, 13, <90kg 18mg, 90-120kg 24mg, >120kg 30mg, this trial uses multiple treatments in the treatment arm (combined with nitazoxanide, ribavirin, and zinc) - results of individual treatments may vary.
Prophylactic Role of Ivermectin in Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Healthcare Workers
Details
Prospective prophylaxis study with 3,532 healthcare workers, 2,199 receiving two-dose ivermectin prophylaxis, showing adjusted relative risk of confirmed COVID-19 with treatment 0.17 [0.12-0.23] p<0.001. 186 patients took only the first d..
Prophylactic Role of Ivermectin in Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Healthcare Workers
Prospective prophylaxis study with 3,532 healthcare workers, 2,199 receiving two-dose ivermectin prophylaxis, showing adjusted relative risk of confirmed COVID-19 with treatment 0.17 [0.12-0.23] p<0.001. 186 patients took only the first dose, and no significant difference was observed for this group. The same group published an earlier small study with 117 ivermectin patients. There were no serious adverse events. T/IM-NF/CM&FM/20/142.
risk of COVID-19 case, 83.0% lower, RR 0.17, p < 0.001, treatment 45 of 2199 (2.0%), control 133 of 1147 (11.6%), two doses.
risk of COVID-19 case, 4.0% higher, RR 1.04, p = 0.85, treatment 23 of 186 (12.4%), control 133 of 1147 (11.6%), patients only receiving the first dose.
Behera et al., 2/15/2021, prospective, India, South Asia, peer-reviewed, 14 authors, dosage 300μg/kg days 1, 4.
Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19, A double-blind, randomized placebo-controlled trial
Details
Double blind RCT for mild-moderate COVID-19 outpatients in Israel showing significantly faster reduction in viral load with treatment, and lower hospitalization with treatment. The one treatment hospitalization was a few hours after treat..
Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19, A double-blind, randomized placebo-controlled trial
Double blind RCT for mild-moderate COVID-19 outpatients in Israel showing significantly faster reduction in viral load with treatment, and lower hospitalization with treatment. The one treatment hospitalization was a few hours after treatment and the patient improved and was discharged quickly. Authors also examine culture viability on days 2-6, with 13% positive in the ivermectin group vs. 48% in the control group. There were no safety issues. Sheba IRB-7156/20. NCT04429711.
risk of hospitalization, 70.2% lower, RR 0.30, p = 0.34, treatment 1 of 47 (2.1%), control 3 of 42 (7.1%).
risk of no virological cure, 44.8% lower, RR 0.55, p = 0.04, treatment 13 of 47 (27.7%), control 21 of 42 (50.0%), adjusted, OR converted to RR, multivariable logistic regression, day 6, Ct>30.
risk of no virological cure, 70.2% lower, RR 0.30, p = 0.14, treatment 2 of 47 (4.3%), control 6 of 42 (14.3%), day 10, non-infectious samples (Ct>30 or non-viable culture).
risk of no virological cure, 82.1% lower, RR 0.18, p = 0.01, treatment 2 of 47 (4.3%), control 10 of 42 (23.8%), day 8, non-infectious samples (Ct>30 or non-viable culture).
risk of no virological cure, 75.6% lower, RR 0.24, p = 0.02, treatment 3 of 47 (6.4%), control 11 of 42 (26.2%), day 6, non-infectious samples (Ct>30 or non-viable culture).
risk of no virological cure, 65.1% lower, RR 0.35, p = 0.05, treatment 4 of 28 (14.3%), control 9 of 22 (40.9%), day 4, non-infectious samples (Ct>30 or non-viable culture).
risk of no virological cure, 51.9% lower, RR 0.48, p = 0.08, treatment 7 of 47 (14.9%), control 13 of 42 (31.0%), day 10, Ct>30.
risk of no virological cure, 57.9% lower, RR 0.42, p = 0.02, treatment 8 of 47 (17.0%), control 17 of 42 (40.5%), day 8, Ct>30.
risk of no virological cure, 44.7% lower, RR 0.55, p = 0.05, treatment 13 of 47 (27.7%), control 21 of 42 (50.0%), day 6, Ct>30.
risk of no virological cure, 31.9% lower, RR 0.68, p = 0.16, treatment 13 of 28 (46.4%), control 15 of 22 (68.2%), day 4, Ct>30.
Biber et al., 2/12/2021, Double Blind Randomized Controlled Trial, Israel, Middle East, preprint, 10 authors, dosage 12mg days 1-3, 15mg for patients >= 70kg.
Effectiveness of a multidrug therapy consisting of ivermectin, azithromycin, montelukast and acetylsalicylic acid to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico
Details
Prospective trial of 768 COVID-19 outpatients in Mexico, 481 treated with ivermectin, AZ, montelukast, and aspirin, and 287 control patients with various treatments, showing significantly lower mortality and hospitalization, and significa..
Effectiveness of a multidrug therapy consisting of ivermectin, azithromycin, montelukast and acetylsalicylic acid to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico
Prospective trial of 768 COVID-19 outpatients in Mexico, 481 treated with ivermectin, AZ, montelukast, and aspirin, and 287 control patients with various treatments, showing significantly lower mortality and hospitalization, and significantly higher recovery at 14 days with treatment.
risk of death, 77.7% lower, RR 0.22, p < 0.001, treatment 15 of 481 (3.1%), control 52 of 287 (18.1%), adjusted, OR converted to RR, multivariate.
risk of hospitalization, 67.4% lower, RR 0.33, p < 0.001, treatment 44 of 481 (9.1%), control 89 of 287 (31.0%), adjusted, OR converted to RR, multivariate.
risk of no recovery, 58.6% lower, RR 0.41, p < 0.001, treatment 75 of 481 (15.6%), control 118 of 287 (41.1%), adjusted, OR converted to RR, recovery at day 14 after symptoms, multivariate.
Lima-Morales et al., 2/10/2021, prospective, Mexico, North America, peer-reviewed, 9 authors, dosage 12mg single dose, this trial uses multiple treatments in the treatment arm (combined with azithromycin, montelukast, and aspirin) - results of individual treatments may vary.
Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): a single-centre randomized, placebo-controlled trial
Details
RCT in India with low risk patients, comparing 24mg ivermectin, 12mg ivermectin, and placebo showing non-statistically significant improvements in recovery and PCR+ status (day 5 both arms, day 7 24mg only) with treatment, and showing gre..
Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): a single-centre randomized, placebo-controlled trial
RCT in India with low risk patients, comparing 24mg ivermectin, 12mg ivermectin, and placebo showing non-statistically significant improvements in recovery and PCR+ status (day 5 both arms, day 7 24mg only) with treatment, and showing greater improvement for the higher dose arm. Viral load decline was similar in all arms - absolute values are lower for ivermectin in a dose-dependent manner, however the baseline value for the ivermectin groups was lower, leaving less room for change. There were no deaths or use of mechanical ventilation. There were no serious adverse events. Note that our pre-specified protocol prioritizes clinical outcomes over PCR results. The supplementary appendix is not currently available.
risk of no discharge at day 14, 62.5% lower, RR 0.38, p = 0.27, treatment 2 of 40 (5.0%), control 6 of 45 (13.3%), ivermectin 24mg.
risk of no discharge at day 14, 43.8% lower, RR 0.56, p = 0.49, treatment 3 of 40 (7.5%), control 6 of 45 (13.3%), ivermectin 12mg.
risk of clinical worsening, 32.5% lower, RR 0.68, p = 0.72, treatment 3 of 40 (7.5%), control 5 of 45 (11.1%), ivermectin 24mg.
risk of clinical worsening, 55.0% lower, RR 0.45, p = 0.44, treatment 2 of 40 (5.0%), control 5 of 45 (11.1%), ivermectin 12mg.
risk of no virological cure, 23.8% lower, RR 0.76, p = 0.18, treatment 21 of 40 (52.5%), control 31 of 45 (68.9%), ivermectin 24mg, day 5.
risk of no virological cure, 5.6% lower, RR 0.94, p = 0.82, treatment 26 of 40 (65.0%), control 31 of 45 (68.9%), ivermectin 12mg, day 5.
risk of no virological cure, 10.3% lower, RR 0.90, p = 0.65, treatment 20 of 36 (55.6%), control 26 of 42 (61.9%), ivermectin 24mg, day 7.
risk of no virological cure, 3.2% higher, RR 1.03, p = 1.00, treatment 23 of 36 (63.9%), control 26 of 42 (61.9%), ivermectin 12mg, day 7.
Mohan et al., 2/2/2021, Double Blind Randomized Controlled Trial, India, South Asia, peer-reviewed, 27 authors, dosage 400μg/kg single dose, 200μg/kg also tested.
Potential use of ivermectin for the treatment and profilaxis of SARS-CoV-2 infection: Efficacy of ivermectin for SARS-CoV-2
Details
Review finding that there appears to be sufficient evidence to recommend ivermectin for the treatment of COVID-19, especially in the early stages of the disease.
Potential use of ivermectin for the treatment and profilaxis of SARS-CoV-2 infection: Efficacy of ivermectin for SARS-CoV-2
Review finding that there appears to be sufficient evidence to recommend ivermectin for the treatment of COVID-19, especially in the early stages of the disease.
Cobos-Campos et al., 1/29/2021, peer-reviewed, 9 authors.
Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis
Details
Student-written meta analysis of a very small subset of studies exhibiting very high bias and significant flaws. Some of the problems:
- As of the publication date, there are 35 studies, authors include only 4. (They list 5, but two are ..
Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis
Student-written meta analysis of a very small subset of studies exhibiting very high bias and significant flaws. Some of the problems:- As of the publication date, there are 35 studies, authors include only 4. (They list 5, but two are the same study, preprint and published version).- From the 17 RCTs, authors include 0.- Authors include only late treatment studies, excluding all 10 early treatment studies and all 10 prophylaxis studies.- Authors did not locate 13 studies, despite this being trivial from existing meta analyses.- There is no logic in the exclusion reasons. For example, they include the most biased study to date, Soto-Becerra, and assign the highest weight to it.- Authors randomly exclude letters but include preprints (excluding letters to help avoid positive results, including preprints to include Soto-Becerra).- Soto-Becerra has clear evidence of extreme bias. The study presents 30 day results and extended KM curves up to day 43 for ivermectin. At 30 days the result is negative but reverts (as do all treatments in the study) and becomes positive before day 43. Authors of this meta analysis ignore the extended followup. Soto-Becerra is a database analysis that includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. More than the total excess mortality happened on the first day. This is consistent with treated patients being in more serious condition, and with many of the control group patients being in hospital for something unrelated to COVID-19. Authors use a machine learning based propensity scoring system that appears over-parameterized and likely to result in significant overfitting and inaccurate results. Essentially they test for all interactions between two and three covariates. The nature and large number of covariates means many random correlations may be found. COVID-19 severity is not used. In summary, this is the lowest quality ivermectin study to date. This study also does not compare treatments with a control group not receiving the treatment - authors put patients receiving treatments after 48 hours in the control group. Authors also state that outcomes within 24 hours were excluded, however KM curves show significant mortality at day 1 (only for the treatment groups).- We checked the reported results for the mortality outcome and found they do not appear to match the actual papers.- Rajter: authors list mortality as 13/85 (treatment), 24/74 (control), the paper shows (for the matched cohort) 13/98 (treatment), 24/98 (control). The adjusted result in the paper is OR 0.27 [0.09-0.80] (multivariate) or OR 0.47 [0.22-0.99] (PSM). These correspond to RR 0.33 and 0.54 respectively, or logRR -1.1 and -0.62. However authors here show logRR 0.54 and 0.85 - they include the study twice (preprint and published). The preprint and published papers have the same multivariate result, the PSM result was added in the published paper. Neither of the two results the authors use match the actual results.- Khan: the paper shows RR 0.13, logRR -2.0. Authors show logRR 0.13.- Soto-Becerra at day 30 shows wHR 1.39 [0.88-2.22], and day 43 weighted KM 0.82 [0.76-0.88]. These correspond to logRR 0.33 and -0.19. Authors show logRR 1.75.- Gorial: there is zero mortality with treatment in this paper. Using the typical continuity correction, the paper shows RR 0.29 when accounting for the different group sizes, or 0.86 when using naive continuity correction that does not account for the very different group sizes. These correspond to logRR -1.24 or -0.15. Authors show logRR 0.60.- Authors did not locate and reference the existing widely known meta-analyses from well-known researchers - Kory et al., Hill et al., Lawrie et al.For more issues see: [1, 2]Authors on Twitter: [3, 4, 5, 6]
Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2
Details
Molecular docking analysis showing that ivermectin efficiently binds to the viral S protein as well as the human cell surface receptors ACE-2 and TMPRSS2; therefore, it might be involved in inhibiting the entry of the virus into the host ..
Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2
Molecular docking analysis showing that ivermectin efficiently binds to the viral S protein as well as the human cell surface receptors ACE-2 and TMPRSS2; therefore, it might be involved in inhibiting the entry of the virus into the host cell. It also binds to Mpro and PLpro of SARS-CoV-2; therefore, it might play a role in preventing the post-translational processing of viral polyproteins. The highly efficient binding of ivermectin to the viral N phosphoprotein and nsp14 is suggestive of its role in inhibiting viral replication and assembly.
Eweas et al., 1/25/2021, peer-reviewed, 3 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
Details
Animal study of a novel spray formulation of ivermectin, showing an advantage of the spray formulation in terms of fast attainment of high and persistent ivermectin concentrations in nasopharyngeal tissue.
Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
Animal study of a novel spray formulation of ivermectin, showing an advantage of the spray formulation in terms of fast attainment of high and persistent ivermectin concentrations in nasopharyngeal tissue.
Errecalde et al., 1/23/2021, peer-reviewed, 15 authors.
Sharp Reductions in COVID-19 Case Fatalities and Excess Deaths in Peru in Close Time Conjunction, State-By-State, with Ivermectin Treatments
Details
Analysis of ivermectin usage within states in Peru showing sharp reductions in COVID-19 deaths corresponding to the usage of ivermectin treatment.
Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents
Details
Computational molecular modeling screening and in vitro analysis for inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme, showing that ivermectin blocked more than 85% of 3CLpro activity of SARS-CoV-2. Antiviral activity of ivermectin..
Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents
Computational molecular modeling screening and in vitro analysis for inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme, showing that ivermectin blocked more than 85% of 3CLpro activity of SARS-CoV-2. Antiviral activity of ivermectin mediated through the blocking of α/β1 importin has been previously established, this analysis suggests an additional antiviral mechanism of ivermectin for SARS-CoV-2 via inhibitory effects on 3CLpro.
Mody et al., 1/20/2021, peer-reviewed, 9 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Effect of ivermectin on COVID-19: A multicenter double-blind randomized controlled clinical trial
Details
RCT in Iran showing shorter time to recovery and shorter hospitalization time with ivermectin. There were no adverse effects. There was one death in the treatment group, the patient was in critical condition at baseline and died within 24..
Effect of ivermectin on COVID-19: A multicenter double-blind randomized controlled clinical trial
RCT in Iran showing shorter time to recovery and shorter hospitalization time with ivermectin. There were no adverse effects. There was one death in the treatment group, the patient was in critical condition at baseline and died within 24 hours of admission. IRCT20111224008507N3. Also see [1] and the author response [2].
risk of death, 197.1% higher, RR 2.97, p = 1.00, treatment 1 of 35 (2.9%), control 0 of 34 (0.0%), continuity correction due to zero event, patient died within 24 hours of admission.
risk of mechanical ventilation, 94.3% higher, RR 1.94, p = 1.00, treatment 2 of 35 (5.7%), control 1 of 34 (2.9%).
recovery time, 31.6% lower, relative time 0.68, p = 0.05, treatment 35, control 34, duration of dsypnea.
recovery time, 19.2% lower, relative time 0.81, p = 0.02, treatment 35, control 34, duration of all symptoms.
hospitalization time, 15.5% lower, relative time 0.85, p = 0.02, treatment 35, control 34.
Shahbaznejad et al., 1/19/2021, Double Blind Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 8 authors, dosage 200μg/kg single dose.
Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection
Details
Meta analysis of 18 ivermectin RCTs with 2,282 patients showing faster viral clearance (dose and duration dependent), improved clinical recovery, and lower hospitalization and mortality. In six RCTs of moderate or severe infection, there ..
Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection
Meta analysis of 18 ivermectin RCTs with 2,282 patients showing faster viral clearance (dose and duration dependent), improved clinical recovery, and lower hospitalization and mortality. In six RCTs of moderate or severe infection, there was a 75% reduction in mortality, RR 0.25 [0.12-0.52], p = 0.0002.A sponsor reportedly required the conclusion of this paper to be changed against the wishes of the authors (to suggest that more trials should be done as opposed to the existing evidence being sufficient) [1, 2, 3]. Note that one of the 18 studies in this analysis has since been withdrawn (Elgazzar).
Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon
Details
RCT 100 patients in Lebanon, showing significantly lower viral load at day 3, and lower hospitalization. All patients also took zinc and vitamin C. ChiCTR2000033627.
Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon
RCT 100 patients in Lebanon, showing significantly lower viral load at day 3, and lower hospitalization. All patients also took zinc and vitamin C. ChiCTR2000033627.
risk of hospitalization, 85.7% lower, RR 0.14, p = 0.24, treatment 0 of 50 (0.0%), control 3 of 50 (6.0%), continuity correction due to zero event.
risk of fever at day 3, 90.9% lower, RR 0.09, p = 0.004, treatment 1 of 50 (2.0%), control 11 of 50 (22.0%).
relative improvement in Ct value at day 3, 68.3% lower, RR 0.32, p < 0.001, treatment 50, control 50.
Samaha et al., 1/16/2021, Randomized Controlled Trial, Lebanon, Middle East, peer-reviewed, 16 authors, dosage 12mg single dose, 45–64kg, 65–84kg, and >85kg patients received 9mg, 12mg, or 150µg/kg respectively.
Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease
Details
RCT of relatively low risk hospitalized patients with 50 ivermectin and 50 control patients showing significantly faster viral clearance with treatment. 9 patients in the treatment arm were lost to followup compared with 5 in the control ..
Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease
RCT of relatively low risk hospitalized patients with 50 ivermectin and 50 control patients showing significantly faster viral clearance with treatment. 9 patients in the treatment arm were lost to followup compared with 5 in the control arm, which could be in part due to faster recovery with treatment. There were no safety concerns. No mortality was reported. The numbers in Table 3 are the number of patients that became negative on that day, i.e., non-cumulative. SOC included vitamin C and vitamin D. NCT04392713.
risk of no virological cure, 82.4% lower, RR 0.18, p < 0.001, treatment 4 of 41 (9.8%), control 25 of 45 (55.6%), day 7.
risk of no virological cure, 38.7% lower, RR 0.61, p < 0.001, treatment 24 of 41 (58.5%), control 43 of 45 (95.6%), day 3.
Bukhari et al., 1/16/2021, Randomized Controlled Trial, Pakistan, South Asia, preprint, 10 authors, dosage 12mg single dose.
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Details
Meta analysis of ivermectin clinical studies and natural experiments where ivermectin has been widely used, showing efficacy of ivermectin in prophylaxis and treatment of COVID-19. This paper was censored by the journal after acceptance [..
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Meta analysis of ivermectin clinical studies and natural experiments where ivermectin has been widely used, showing efficacy of ivermectin in prophylaxis and treatment of COVID-19. This paper was censored by the journal after acceptance [1].
Evaluation of the Effectiveness and Safety of Adding Ivermectin to Treatment in Severe COVID-19 Patients
Details
Small RCT for severe COVID-19 comparing the addition of ivermectin to SOC (low dose HCQ+AZ+favipiravir), with 30 treatment and 30 control patients in Turkey, showing lower mortality and faster clinical recovery. Authors also investigate t..
Evaluation of the Effectiveness and Safety of Adding Ivermectin to Treatment in Severe COVID-19 Patients
Small RCT for severe COVID-19 comparing the addition of ivermectin to SOC (low dose HCQ+AZ+favipiravir), with 30 treatment and 30 control patients in Turkey, showing lower mortality and faster clinical recovery. Authors also investigate the presence of gene mutations that alter ivermectin metabolism, predicting that ivermectin can be used safely without serious side effects in patients without MDR-1/ABCB1 and/or CYP3A4 gene mutation, and recommending monitoring and appropriate treatment if necessary when sequencing is unavailable. NCT04646109.
risk of death, 33.3% lower, RR 0.67, p = 0.55, treatment 6 of 30 (20.0%), control 9 of 30 (30.0%).
risk of no improvement at day 10, 42.9% lower, RR 0.57, p = 0.18, treatment 8 of 30 (26.7%), control 14 of 30 (46.7%).
risk of no improvement at day 5, 15.8% lower, RR 0.84, p = 0.60, treatment 16 of 30 (53.3%), control 19 of 30 (63.3%).
risk of no virological cure, 80.0% lower, RR 0.20, p = 0.02, treatment 2 of 16 (12.5%), control 5 of 8 (62.5%), day 10.
A randomized trial - intensive treatment based in ivermectin and iota-carrageenan as pre-exposure prophylaxis for COVID-19 in healthcare agents
Details
Prophylaxis RCT for ivermectin and iota-carrageenan in Argentina, 117 healthcare workers treated with ivermectin and iota-carrageenan, and 117 controls, showing significantly lower cases with treatment. There were no moderate/severe cases..
A randomized trial - intensive treatment based in ivermectin and iota-carrageenan as pre-exposure prophylaxis for COVID-19 in healthcare agents
Prophylaxis RCT for ivermectin and iota-carrageenan in Argentina, 117 healthcare workers treated with ivermectin and iota-carrageenan, and 117 controls, showing significantly lower cases with treatment. There were no moderate/severe cases with treatment vs. 10 in the control group. There were 4 cases with treatment (all mild) vs. 25 for the control group. NCT04701710.
risk of moderate/severe case, 95.2% lower, RR 0.05, p = 0.002, treatment 0 of 117 (0.0%), control 10 of 117 (8.5%), continuity correction due to zero event, moderate/severe COVID-19.
risk of COVID-19 case, 84.0% lower, RR 0.16, p = 0.001, treatment 4 of 117 (3.4%), control 25 of 117 (21.4%), adjusted, OR converted to RR, all cases.
Chahla et al., 1/11/2021, Randomized Controlled Trial, Argentina, South America, peer-reviewed, 11 authors, dosage 12mg weekly, this trial uses multiple treatments in the treatment arm (combined with iota-carrageenan) - results of individual treatments may vary.
Large Impact of obesity on the disposition of ivermectin, moxidectin and eprinomectin in a canine model: relevance for COVID-19 patients
Details
Animal dosing study with an obese dog model concluding that ivermectin maintenance doses should be based on lean body weight and not the total body weight in obese subjects, while the loading dose should be based on the total body weight.
Large Impact of obesity on the disposition of ivermectin, moxidectin and eprinomectin in a canine model: relevance for COVID-19 patients
Animal dosing study with an obese dog model concluding that ivermectin maintenance doses should be based on lean body weight and not the total body weight in obese subjects, while the loading dose should be based on the total body weight.
Bousquet-Melou et al., 1/11/2021, preprint, 5 authors.
Ivermectin: an award-winning drug with expected antiviral activity against COVID-19
Details
Review hypothesizing that micro- and nanotechnology-based formulations of ivermectin for the pulmonary delivery of ivermectin may be beneficial for use with COVID-19.
Ivermectin: an award-winning drug with expected antiviral activity against COVID-19
Review hypothesizing that micro- and nanotechnology-based formulations of ivermectin for the pulmonary delivery of ivermectin may be beneficial for use with COVID-19.
Formiga et al., 1/10/2021, peer-reviewed, 6 authors.
Ravikirti et al., Journal of Pharmacy & Pharmaceutical Sciences, doi:10.18433/jpps32105 (Peer Reviewed)
death, ↓88.7%, p=0.12
Ivermectin as a potential treatment for mild to moderate COVID-19: A double blind randomized placebo-controlled trial
Details
RCT with 112 mild and moderate COVID-19 patients in India, showing lower mortality, ventilation, and ICU admission, although not statistically significant due to the small number of events. There was no mortality in the treatment arm (55 ..
Ravikirti et al., Journal of Pharmacy & Pharmaceutical Sciences, doi:10.18433/jpps32105 (Peer Reviewed)
Ivermectin as a potential treatment for mild to moderate COVID-19: A double blind randomized placebo-controlled trial
RCT with 112 mild and moderate COVID-19 patients in India, showing lower mortality, ventilation, and ICU admission, although not statistically significant due to the small number of events. There was no mortality in the treatment arm (55 patients) versus 7% (4 of 57) in the control arm. The PCR result is subject to confounding by biased loss of followup, with 23 lost in the treatment group and 13 in the control group, and 8 more people in the treatment group discharged before day 6.
risk of death, 88.7% lower, RR 0.11, p = 0.12, treatment 0 of 55 (0.0%), control 4 of 57 (7.0%), continuity correction due to zero event.
risk of mechanical ventilation, 79.3% lower, RR 0.21, p = 0.10, treatment 1 of 55 (1.8%), control 5 of 57 (8.8%).
risk of ICU admission, 13.6% lower, RR 0.86, p = 0.80, treatment 5 of 55 (9.1%), control 6 of 57 (10.5%).
risk of no hospital discharge, 88.7% lower, RR 0.11, p = 0.12, treatment 0 of 55 (0.0%), control 4 of 57 (7.0%), continuity correction due to zero event.
risk of no virological cure, 11.6% higher, RR 1.12, p = 0.35, treatment 42 of 55 (76.4%), control 39 of 57 (68.4%).
Ravikirti et al., 1/9/2021, Double Blind Randomized Controlled Trial, India, South Asia, peer-reviewed, 11 authors, dosage 12mg days 1, 2.
Babalola et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcab035 (preprint 1/6) (Peer Reviewed)
viral+, ↓63.9%, p=0.11
Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos
Details
Small RCT comparing ivermectin 6mg & 12mg q84hr with lopinavir/ritonavir, showing a statistically significant and dose dependent effect of ivermectin on reducing the time to PCR-.
The study does not report mortality, hospitalization, pro..
Babalola et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcab035 (preprint 1/6) (Peer Reviewed)
Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos
Small RCT comparing ivermectin 6mg & 12mg q84hr with lopinavir/ritonavir, showing a statistically significant and dose dependent effect of ivermectin on reducing the time to PCR-.The study does not report mortality, hospitalization, progression, recovery, etc. The paper does report change in SpO2 (Figure 3, ∆SpO2), where a similar improvement with a smaller p value is seen with ivermectin, however this result is unadjusted and there are large differences between groups. Specifically, baseline SpO2 is lower in the control group, giving the control group more room to improve, therefore the actual benefit of ivermectin is likely to be even larger than the benefit in ∆SpO2 shown.
adjusted risk of viral+ at day 5, 63.9% lower, RR 0.36, p = 0.11, treatment 40, control 20, adjusted.
relative ∆SpO2, 41.5% lower, RR 0.59, p = 0.07, treatment 38, control 18, figure 3.
risk of no virological cure, 58.0% lower, RR 0.42, p = 0.01, treatment 20, control 20, 12mg - Cox proportional hazard model.
risk of no virological cure, 40.5% lower, RR 0.60, p = 0.12, treatment 20, control 20, 6mg - Cox proportional hazard model.
time to viral-, 49.2% lower, relative time 0.51, p = 0.02, treatment 20, control 20, 12mg.
time to viral-, 34.4% lower, relative time 0.66, p = 0.08, treatment 20, control 20, 6mg.
Babalola et al., 1/6/2021, Double Blind Randomized Controlled Trial, Nigeria, Africa, peer-reviewed, baseline oxygen requirements 8.3%, 10 authors, dosage 12mg or 6mg q84h for two weeks, this trial compares with another treatment - results may be better when compared to placebo.
Hirsch et al., Microbiology & Infectious Diseases (Peer Reviewed)
Ivermectin as Prophylaxis Against COVID-19 Retrospective Cases Evaluation
Details
Report on ivermectin prophylaxis for healthcare workers in a hospital in Argentina, showing 0 cases in the 162 participants. Dosage was 0.2mg/kg weekly for eight weeks, followed by 4 months rest.
Hirsch et al., Microbiology & Infectious Diseases (Peer Reviewed)
Ivermectin as Prophylaxis Against COVID-19 Retrospective Cases Evaluation
Report on ivermectin prophylaxis for healthcare workers in a hospital in Argentina, showing 0 cases in the 162 participants. Dosage was 0.2mg/kg weekly for eight weeks, followed by 4 months rest.
Hirsch et al., 1/6/2021, peer-reviewed, 2 authors.
Lawrie et al., Preprint (Preprint) (meta analysis)
death, ↓83.0%, p<0.0001
Ivermectin reduces the risk of death from COVID-19 – a rapid review and meta-analysis in support of the recommendation of the Front Line COVID-19 Critical Care Alliance
Details
Meta analysis confirming the effectiveness of ivermectin for COVID-19, showing ivermectin treatment mortality relative risk RR 0.17 [0.18-0.35] and prophylaxis cases RR 0.12 [0.08-0.18].
Lawrie et al., Preprint (Preprint) (meta analysis)
Ivermectin reduces the risk of death from COVID-19 – a rapid review and meta-analysis in support of the recommendation of the Front Line COVID-19 Critical Care Alliance
Meta analysis confirming the effectiveness of ivermectin for COVID-19, showing ivermectin treatment mortality relative risk RR 0.17 [0.18-0.35] and prophylaxis cases RR 0.12 [0.08-0.18].
risk of death, 83.0% lower, RR 0.17, p < 0.001, treatment 8 of 585 (1.4%), control 44 of 522 (8.4%).
Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)
Details
Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may ..
Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)
Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may include >=2 of HCQ, ivermectin, favipiravir; AZM/DOXY; corticosteroids; colchicine; bamlanivimab; aspirin; LMWH; and supplemental oxygen.
McCullough et al., 12/30/2020, peer-reviewed, 58 authors.
Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection
Details
Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region.
At least two of z..
Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection
Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region.At least two of zinc, HCQ, and ivermectin were used, along with one antibiotic, and budesonide and/or dexamethasone.
Procter et al., 12/30/2020, peer-reviewed, 6 authors.
Meta-analysis of clinical trials of ivermectin to treat COVID-19 infection
Details
WHO-funded meta analysis showing ivermectin treatment mortality relative risk RR 0.17 [0.08-0.35] for RCTs and RR 0.28 [0.13-0.62] for RCTs and observational studies, and confirming a dose-response effect.
Meta-analysis of clinical trials of ivermectin to treat COVID-19 infection
WHO-funded meta analysis showing ivermectin treatment mortality relative risk RR 0.17 [0.08-0.35] for RCTs and RR 0.28 [0.13-0.62] for RCTs and observational studies, and confirming a dose-response effect.
Details
Report on ivermectin prophylaxis in a hospital in Argentina showing lower cases for healthcare workers taking ivermectin. Preliminary results from: [1]. Note that this prophylaxis trial is a different study to the early treatment Vallejos..
Report on ivermectin prophylaxis in a hospital in Argentina showing lower cases for healthcare workers taking ivermectin. Preliminary results from: [1]. Note that this prophylaxis trial is a different study to the early treatment Vallejos trial.
Kory et al., FLCCC Alliance (Preprint) (meta analysis)
death, ↓69.0%, p<0.0001
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Details
Meta analysis of ivermectin clinical studies and natural experiments where ivermectin has been widely used, showing efficacy of ivermectin in prophylaxis and treatment of COVID-19.
Kory et al., FLCCC Alliance (Preprint) (meta analysis)
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Meta analysis of ivermectin clinical studies and natural experiments where ivermectin has been widely used, showing efficacy of ivermectin in prophylaxis and treatment of COVID-19.
risk of death, 69.0% lower, RR 0.31, p < 0.001, treatment 35 of 1551 (2.3%), control 191 of 1957 (9.8%), OR converted to RR.
Ivermectin Use Associated with Reduced Duration of COVID-19 Febrile Illness in a Community Setting
Details
Small 95 patient study in Pakistan adding ivermectin to standard of care (HCQ+AZ) for outpatients with mild/moderate suspected COVID-19, showing faster resolution of fever with ivermectin. The low dose HCQ used in this study may not reach..
Ivermectin Use Associated with Reduced Duration of COVID-19 Febrile Illness in a Community Setting
Small 95 patient study in Pakistan adding ivermectin to standard of care (HCQ+AZ) for outpatients with mild/moderate suspected COVID-19, showing faster resolution of fever with ivermectin. The low dose HCQ used in this study may not reach therapeutic levels fast enough to make a significant impact.
duration of fever, 98.0% lower, relative time 0.02, p < 0.001, treatment 0 of 37 (0.0%), control 7 of 53 (13.2%), adjusted, continuity correction due to zero event, logistic regression.
Afsar et al., 12/15/2020, retrospective, Pakistan, South Asia, preprint, 6 authors, dosage 12mg days 1-6.
The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial
Details
Tiny RCT for early treatment of mild COVID-19 in low risk patients, with 12 400mcg/kg single dose ivermectin patients and 12 control patients, showing significantly faster viral load reduction and symptom improvement with ivermectin. Aver..
The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial
Tiny RCT for early treatment of mild COVID-19 in low risk patients, with 12 400mcg/kg single dose ivermectin patients and 12 control patients, showing significantly faster viral load reduction and symptom improvement with ivermectin. Average median viral load for gene E and gene N mid-viral recovery at day 7: Ivermectin: 1637, control: 30175 (supplementary appendix). NCT04390022.
risk of symptoms, 96.0% lower, RR 0.04, p < 0.05, treatment 12, control 12, logistic regression, chance of presenting any symptom, RR approximated with OR.
viral load, 94.6% lower, relative load 0.05, p < 0.01, treatment 12, control 12, day 7 mid-recovery, average of gene E and gene N, data in supplementary appendix.
risk of no virological cure, 8.0% lower, RR 0.92, p = 1.00, treatment 12, control 12.
Chaccour et al., 12/7/2020, Double Blind Randomized Controlled Trial, Spain, Europe, peer-reviewed, 23 authors, dosage 400μg/kg single dose.
The therapeutic potential of ivermectin for COVID-19: a systematic review of mechanisms and evidence
Details
Review of ivermectin mechanisms and 8 trials, showing positive mortality benefit, reduced time to clinical recovery, reduced incidence of disease progression, and decreased duration of hospital admission in patients across all stages of c..
The therapeutic potential of ivermectin for COVID-19: a systematic review of mechanisms and evidence
Review of ivermectin mechanisms and 8 trials, showing positive mortality benefit, reduced time to clinical recovery, reduced incidence of disease progression, and decreased duration of hospital admission in patients across all stages of clinical severity.
Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19
DetailsIn Vitro analysis of ivermectin with orally administrable nanoparticles showing efficacy for decreasing expression of the viral spike protein and ACE2. Inhibition of nuclear transport activities mediated through proteins such as importin ..
Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19
In Vitro analysis of ivermectin with orally administrable nanoparticles showing efficacy for decreasing expression of the viral spike protein and ACE2. Inhibition of nuclear transport activities mediated through proteins such as importin α/β1 heterodimer are also considered as a possible mechanism of action. The technology may work for other coronaviruses as well.
Surnar et al., 12/4/2020, peer-reviewed, 4 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
A five day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness
Details
Small 72 patient RCT of ivermectin and ivermectin + doxycycline showing faster recovery with ivermectin.
Ivermectin group: 12mg daily for 5 days
Ivermectin + doxycycline: 12mg ivermectin single dose, 200mg doxycycline + 100mg bid 4 days
A five day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness
Small 72 patient RCT of ivermectin and ivermectin + doxycycline showing faster recovery with ivermectin.Ivermectin group: 12mg daily for 5 days Ivermectin + doxycycline: 12mg ivermectin single dose, 200mg doxycycline + 100mg bid 4 days
risk of unresolved symptoms, 85.0% lower, RR 0.15, p = 0.09, treatment 0 of 17 (0.0%), control 3 of 19 (15.8%), continuity correction due to zero event, day 7 fever ivermectin.
risk of unresolved symptoms, 62.7% lower, RR 0.37, p = 0.35, treatment 1 of 17 (5.9%), control 3 of 19 (15.8%), day 7 fever ivermectin + doxycycline.
risk of no virological cure, 75.6% lower, RR 0.24, p = 0.03, treatment 11 of 22 (50.0%), control 20 of 23 (87.0%), adjusted, day 7 ivermectin.
risk of no virological cure, 56.5% lower, RR 0.43, p = 0.22, treatment 16 of 23 (69.6%), control 20 of 23 (87.0%), adjusted, day 7 ivermectin + doxycycline.
risk of no virological cure, 63.0% lower, RR 0.37, p = 0.02, treatment 5 of 22 (22.7%), control 14 of 23 (60.9%), adjusted, day 14 ivermectin.
risk of no virological cure, 41.2% lower, RR 0.59, p = 0.19, treatment 9 of 23 (39.1%), control 14 of 23 (60.9%), adjusted, day 14 ivermectin + doxycycline.
time to viral-, 23.6% lower, relative time 0.76, p = 0.02, treatment 22, control 23, ivermectin.
time to viral-, 9.4% lower, relative time 0.91, p = 0.27, treatment 23, control 23, ivermectin + doxycycline.
hospitalization time, 1.0% lower, relative time 0.99, ivermectin.
hospitalization time, 4.1% higher, relative time 1.04, ivermectin + doxycycline.
Ahmed et al., 12/2/2020, Double Blind Randomized Controlled Trial, Bangladesh, South Asia, peer-reviewed, mean age 42.0, 15 authors, dosage 12mg days 1-5, ivermectin + doxycycline group took only a single dose of ivermectin.
The effect of using ivermectin to control COVID-19 in Chiapas
Details
After starting to distribute ivermectin in drug kits in July, the Mexican state of Chiapas has seen a dramatic divergence from other states with much lower mortality [1, 2].
The effect of using ivermectin to control COVID-19 in Chiapas
After starting to distribute ivermectin in drug kits in July, the Mexican state of Chiapas has seen a dramatic divergence from other states with much lower mortality [1, 2].
Details
Observational study in Argentina showing significantly lower mortality in the 60 days after adopting ivermectin compared to the 60 days before, relative risk RR 0.082, p=0.003.
Observational study in Argentina showing significantly lower mortality in the 60 days after adopting ivermectin compared to the 60 days before, relative risk RR 0.082, p=0.003.
risk of death, 91.8% lower, RR 0.08, p = 0.009, treatment 1 of 311 (0.3%), control 5 of 128 (3.9%).
Alonso et al., 12/1/2020, retrospective, Argentina, South America, preprint, 1 author, dosage not specified.
Ivermectin benefit: from scabies to COVID-19, an example of serendipity
Details
69 residents of a French care home, median age 90, were treated with ivermectin for a scabies outbreak. 3,062 residents in 45 nearby comparable homes were used as controls. 7 of 69 treated patients had probable or certain COVID-19, with n..
Ivermectin benefit: from scabies to COVID-19, an example of serendipity
69 residents of a French care home, median age 90, were treated with ivermectin for a scabies outbreak. 3,062 residents in 45 nearby comparable homes were used as controls. 7 of 69 treated patients had probable or certain COVID-19, with no serious cases and no deaths. In comparable care homes in the same district, matched by age and socio-economic level, there was 22.6% COVID-19 and 5% death.
risk of death, 99.4% lower, RR 0.006, p = 0.08, treatment 0 of 69 (0.0%), control 150 of 3062 (4.9%), continuity correction due to zero event.
risk of COVID-19 case, 55.1% lower, RR 0.45, p = 0.01, treatment 7 of 69 (10.1%), control 692 of 3062 (22.6%).
Bernigaud et al., 11/28/2020, retrospective, France, Europe, peer-reviewed, 12 authors, dosage 200μg/kg days 1, 8, 15, 400μg/kg days 1, 8, 15, two different dosages.
A COVID-19 Prophylaxis? Lower incidence associated with prophylactic administration of Ivermectin
Details
Analysis of COVID-19 cases vs. widespread prophylactic use of ivermectin for parasitic infections showing significantly lower incidence of COVID-19 cases.
A COVID-19 Prophylaxis? Lower incidence associated with prophylactic administration of Ivermectin
Analysis of COVID-19 cases vs. widespread prophylactic use of ivermectin for parasitic infections showing significantly lower incidence of COVID-19 cases.
risk of COVID-19 case, 78.0% lower, RR 0.22, p < 0.02, African countries, PCTI vs. no PCT, relative cases per capita.
risk of COVID-19 case, 80.0% lower, RR 0.20, p < 0.001, worldwide, PCTI vs. no PCT, relative cases per capita.
Hellwig et al., 11/28/2020, retrospective, ecological study, multiple countries, multiple regions, peer-reviewed, 2 authors, dosage 200μg/kg, dose varied, typically 150-200μg/kg.
Niaee et al., Asian Pacific Journal of Tropical Medicine, doi:10.4103/1995-7645.318304 (preprint 11/24/20) (Peer Reviewed)
death, ↓81.8%, p=0.001
Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial
Details
82% lower mortality with ivermectin. RCT with 180 hospitalized patients showing reduced mortality and hospital stay with ivermectin, with a wide margin of safety. All patients received SOC including low dose HCQ.
Niaee et al., Asian Pacific Journal of Tropical Medicine, doi:10.4103/1995-7645.318304 (preprint 11/24/20) (Peer Reviewed)
Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial
82% lower mortality with ivermectin. RCT with 180 hospitalized patients showing reduced mortality and hospital stay with ivermectin, with a wide margin of safety. All patients received SOC including low dose HCQ.
risk of death, 81.8% lower, RR 0.18, p = 0.001, treatment 4 of 120 (3.3%), control 11 of 60 (18.3%), All IVM vs. all control.
risk of death, 94.3% lower, RR 0.06, p = 0.01, treatment 0 of 30 (0.0%), control 11 of 60 (18.3%), continuity correction due to zero event, IVM single dose 200mcg/kg vs. all control.
risk of death, 45.5% lower, RR 0.55, p = 0.37, treatment 3 of 30 (10.0%), control 11 of 60 (18.3%), IVM three dose 200mcg/kg vs. all control.
risk of death, 94.3% lower, RR 0.06, p = 0.01, treatment 0 of 30 (0.0%), control 11 of 60 (18.3%), continuity correction due to zero event, IVM single dose 400mcg/kg vs. all control.
risk of death, 81.8% lower, RR 0.18, p = 0.06, treatment 1 of 30 (3.3%), control 11 of 60 (18.3%), IVM three dose 400/200/200mcg/kg vs. all control.
Niaee et al., 11/24/2020, Double Blind Randomized Controlled Trial, Iran, Middle East, peer-reviewed, mean age 56.0, 14 authors, dosage 400μg/kg single dose, dose varies in different groups.
Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin
Details
Animal study showing that standard doses of ivermectin prevented clinical deterioration, reduced olfactory deficit, and limited the inflammation of the upper and lower respiratory tracts in SARS-CoV-2-infected hamsters.
Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin
Animal study showing that standard doses of ivermectin prevented clinical deterioration, reduced olfactory deficit, and limited the inflammation of the upper and lower respiratory tracts in SARS-CoV-2-infected hamsters.
de Melo et al., 11/22/2020, peer-reviewed, 11 authors.
Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience
Retrospective 976 hospitalized patients with 34 treated with ivermectin showing ivermectin mortality relative risk RR 0.13, p = 0.04 in unadjusted results.
risk of death, 99.1% lower, RR 0.009, p = 0.04, treatment 0 of 34 (0.0%), control 103 of 942 (10.9%), continuity correction due to zero event, unadjusted.
Budhiraja et al., 11/18/2020, retrospective, India, South Asia, preprint, 12 authors, dosage not specified.
Carvallo et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1007 (Peer Reviewed)
cases, ↓99.9%, p<0.0001
Study of the Efficacy and Safety of Topical Ivermectin + Iota-Carrageenan in the Prophylaxis against COVID-19 in Health Personnel
Details
Prophylaxis study using ivermectin and iota-carrageenan showing 0 of 788 cases from treated healthcare workers, compared to 237 of 407 control.
The authors later reported that carrageenan is not necessary in this protocol [1].
Carvallo et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1007 (Peer Reviewed)
Study of the Efficacy and Safety of Topical Ivermectin + Iota-Carrageenan in the Prophylaxis against COVID-19 in Health Personnel
Prophylaxis study using ivermectin and iota-carrageenan showing 0 of 788 cases from treated healthcare workers, compared to 237 of 407 control.The authors later reported that carrageenan is not necessary in this protocol [1].
risk of COVID-19 case, 99.9% lower, RR 0.001, p < 0.001, treatment 0 of 788 (0.0%), control 237 of 407 (58.2%), continuity correction due to zero event.
Carvallo et al., 11/17/2020, prospective, Argentina, South America, peer-reviewed, 4 authors, dosage 12mg weekly, this trial uses multiple treatments in the treatment arm (combined with iota-carrageenan) - results of individual treatments may vary.
Spoorthi et al., IAIM, 2020, 7:10, 177-182 (Peer Reviewed)
Utility of Ivermectin and Doxycycline combination for the treatment of SARSCoV-2
100 patient prospective trial of ivermectin + doxycycline showing reduced time to symptom resolution and shorter hospital stay with treatment.
recovery time, 21.1% lower, relative time 0.79, p = 0.03, treatment 50, control 50.
hospitalization time, 15.5% lower, relative time 0.84, p = 0.01, treatment 50, control 50.
Spoorthi et al., 11/14/2020, prospective, India, South Asia, peer-reviewed, 2 authors, dosage not specified, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.
Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients
Details
Tiny 26 patient retrospective study of very late treatment with ivermectin 200 μg/kg, median 12 days after symptoms, not showing significant differences. Authors suggest the dose is too low and recommend evaluation of higher doses. All pa..
Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients
Tiny 26 patient retrospective study of very late treatment with ivermectin 200 μg/kg, median 12 days after symptoms, not showing significant differences. Authors suggest the dose is too low and recommend evaluation of higher doses. All patients received HCQ which may reduce the potential benefit for adding ivermectin.
risk of mechanical ventilation, 40.0% lower, RR 0.60, p = 0.67, treatment 3 of 13 (23.1%), control 5 of 13 (38.5%).
risk of ICU admission, 33.3% lower, RR 0.67, p = 1.00, treatment 2 of 13 (15.4%), control 3 of 13 (23.1%), ICU at day 8.
risk of no improvement at day 8, 33.3% higher, RR 1.33, p = 1.00, treatment 4 of 13 (30.8%), control 3 of 13 (23.1%).
risk of no virological cure, 25.0% higher, RR 1.25, p = 1.00, treatment 5 of 13 (38.5%), control 4 of 13 (30.8%), tests done between days 3-5.
Camprubí et al., 11/11/2020, retrospective, Spain, Europe, peer-reviewed, 9 authors, dosage 200μg/kg single dose.
FLCCC Alliance MATH+ ascorbic acid and I-MASK+ ivermectin protocols for COVID-19 — a brief review
Details
Review suggesting that ivermectin should be used based on existing data suggesting significant benefits, and that waiting for additional data may result in significant harm.
FLCCC Alliance MATH+ ascorbic acid and I-MASK+ ivermectin protocols for COVID-19 — a brief review
Review suggesting that ivermectin should be used based on existing data suggesting significant benefits, and that waiting for additional data may result in significant harm.
Early COVID-19 Therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in Outpatient Settings Significantly Improved COVID-19 outcomes compared to Known outcomes in untreated patients
Details
Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, ev..
Early COVID-19 Therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in Outpatient Settings Significantly Improved COVID-19 outcomes compared to Known outcomes in untreated patients
Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.
risk of death, 78.3% lower, RR 0.22, p = 0.50, treatment 0 of 110 (0.0%), control 2 of 137 (1.5%), continuity correction due to zero event, control group 1.
risk of mechanical ventilation, 94.2% lower, RR 0.06, p = 0.005, treatment 0 of 110 (0.0%), control 9 of 137 (6.6%), continuity correction due to zero event, control group 1.
risk of hospitalization, 98.0% lower, RR 0.02, p < 0.001, treatment 0 of 110 (0.0%), control 27 of 137 (19.7%), continuity correction due to zero event, control group 1.
Cadegiani et al., 11/4/2020, prospective, Brazil, South America, peer-reviewed, 4 authors, dosage 200μg/kg days 1-3, this trial uses multiple treatments in the treatment arm (combined with AZ, nitazoxanide (82), HCQ (22), spironolactone (66), dutasteride (4)) - results of individual treatments may vary.
Morgenstern et al., J. Clinical Trials (preprint 11/3) (Peer Reviewed)
The Use of Compassionate Ivermectin in the Management of SymptomaticOutpatients and Hospitalized Patients with Clinical Diagnosis of Covid-19 at theCentro Medico Bournigal and at the Centro Medico Punta Cana, GrupoRescue, Dominican Republic, from May 1 to August 10, 2020
Details
Retrospective 3,099 outpatients treated with ivermectin in an ER. Of 2,706 treated on an outpatient basis, 18 were subsequently hospitalized, 2 in the ICU, and there was one death (0.04%).
The average treatment delay for patients treated..
Morgenstern et al., J. Clinical Trials (preprint 11/3) (Peer Reviewed)
The Use of Compassionate Ivermectin in the Management of SymptomaticOutpatients and Hospitalized Patients with Clinical Diagnosis of Covid-19 at theCentro Medico Bournigal and at the Centro Medico Punta Cana, GrupoRescue, Dominican Republic, from May 1 to August 10, 2020
Retrospective 3,099 outpatients treated with ivermectin in an ER. Of 2,706 treated on an outpatient basis, 18 were subsequently hospitalized, 2 in the ICU, and there was one death (0.04%).The average treatment delay for patients treated on an outpatient basis was 3.6 days, compared to 6.9 days for hospitalized patients, and 7.8 days for ICU patients.For the 300 late treatment hospitalized patients there was 3 deaths. For the 111 very late treatment ICU patients there was 34 deaths.
Morgenstern et al., 11/3/2020, peer-reviewed, 14 authors.
Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
Details
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin.
HCQ OR 0.56, ..
Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin.HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58
risk of COVID-19 case, 53.8% lower, RR 0.46, p < 0.001, treatment 41 of 117 (35.0%), control 145 of 255 (56.9%), adjusted, OR converted to RR, model 2 2+ doses conditional logistic regression.
risk of COVID-19 case, 44.5% lower, RR 0.56, p < 0.001, treatment 41 of 117 (35.0%), control 145 of 255 (56.9%), OR converted to RR, matched pair analysis.
Behera et al., 11/3/2020, retrospective, India, South Asia, peer-reviewed, 13 authors, dosage 300μg/kg days 1, 4.
COVID-19: Effectiveness of pre-exposure prophylaxis with ivermectin in exposed persons
Details
Pre-exposure prophylaxis study with 129 people split into high/low exposure groups, with each group split into different dosing regimens, showing higher effectivess with more frequent doses.
High-exposure group:
every 7 days dosing: 0 o..
COVID-19: Effectiveness of pre-exposure prophylaxis with ivermectin in exposed persons
Pre-exposure prophylaxis study with 129 people split into high/low exposure groups, with each group split into different dosing regimens, showing higher effectivess with more frequent doses.High-exposure group:every 7 days dosing: 0 of 20 cases, 100% effective every 14 days dosing: 1 of 47 cases, 98% effective every 30 days dosing: 2 of 20 cases, 90% effectiveLow-exposure group:every 14 days dosing: 0 of 21 cases, 100% effective every 30 days dosing: 1 of 20 cases, 95% effective
Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis
Details
Retrospective 717 patients in Brazil showing OR 1.17 [0.72-1.90] for ivermectin. This paper focuses on HCQ, event counts for ivermectin are not provided. With significant correlation between the variables used, including overlap in the pr..
Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis
Retrospective 717 patients in Brazil showing OR 1.17 [0.72-1.90] for ivermectin. This paper focuses on HCQ, event counts for ivermectin are not provided. With significant correlation between the variables used, including overlap in the prescription of multiple treatments that show efficacy alone, and limited data for the model size, the model used here may be inaccurate due to multicollinearity [1].
risk of hospitalization, 13.9% higher, RR 1.14, p = 0.45, treatment 340, control 377, adjusted, OR converted to RR, control prevalence approximated with overall prevalence.
Szente Fonseca et al., 10/31/2020, retrospective, Brazil, South America, peer-reviewed, mean age 50.6, 10 authors, dosage 12mg days 1-2.
Hashim et al., Iraqi Journal of Medical Science, 19:1 (Peer Reviewed)
death, ↓91.7%, p=0.03
Controlled randomized clinical trial on using Ivermectin with doxycycline for treating COVID-19 patients in Baghdad, Iraq
Details
RCT 70 ivermectin+doxycycline patients and 70 control patients showing reduced time to recovery and reduced mortality with treatment. Earlier treatment was more successful. For ethical reasons, critical patients were all in the treatment ..
Hashim et al., Iraqi Journal of Medical Science, 19:1 (Peer Reviewed)
Controlled randomized clinical trial on using Ivermectin with doxycycline for treating COVID-19 patients in Baghdad, Iraq
RCT 70 ivermectin+doxycycline patients and 70 control patients showing reduced time to recovery and reduced mortality with treatment. Earlier treatment was more successful. For ethical reasons, critical patients were all in the treatment group. NCT04591600.
risk of death, 91.7% lower, RR 0.08, p = 0.03, treatment 0 of 59 (0.0%), control 6 of 70 (8.6%), continuity correction due to zero event, excluding non-randomized critical patients.
risk of death, 67.1% lower, RR 0.33, p = 0.16, treatment 2 of 70 (2.9%), control 6 of 70 (8.6%), OR converted to RR, including critical patients that were always allocated to treatment.
risk of disease progression, 83.1% lower, RR 0.17, p = 0.07, treatment 1 of 59 (1.7%), control 7 of 70 (10.0%), excluding non-randomized critical patients.
risk of disease progression, 57.4% lower, RR 0.43, p = 0.20, treatment 3 of 70 (4.3%), control 7 of 70 (10.0%), OR converted to RR, including critical patients that were always allocated to treatment.
recovery time, 40.7% lower, relative time 0.59, p < 0.001, treatment 70, control 70.
Hashim et al., 10/26/2020, Single Blind Randomized Controlled Trial, Iraq, Middle East, peer-reviewed, 7 authors, dosage 200μg/kg days 1-2, some patients received a third dose on day 8, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.
Details
Study of African Programme for Onchocerciasis Control (APOC) countries, which used ivermectin, with non-APOC countries in Africa, showing 28% lower mortality for APOC countries, relative risk RR = 0.72 [0.67-0.78]. See also [1] and the au..
Study of African Programme for Onchocerciasis Control (APOC) countries, which used ivermectin, with non-APOC countries in Africa, showing 28% lower mortality for APOC countries, relative risk RR = 0.72 [0.67-0.78]. See also [1] and the author's response [2].
Usefulness of Topic Ivermectin and Carrageenan to Prevent Contagion of Covid 19 (IVERCAR)
Details
Prophylaxis study using ivermectin and carrageenan showing 0 of 131 cases from treated healthcare workers, compared to 11 of 98 control.
The effect is likely to be primarily due to ivermectin - the author has later reported that carragee..
Usefulness of Topic Ivermectin and Carrageenan to Prevent Contagion of Covid 19 (IVERCAR)
Prophylaxis study using ivermectin and carrageenan showing 0 of 131 cases from treated healthcare workers, compared to 11 of 98 control.The effect is likely to be primarily due to ivermectin - the author has later reported that carrageenan is not necessary [1].
risk of COVID-19 case, 96.3% lower, RR 0.04, p < 0.001, treatment 0 of 131 (0.0%), control 11 of 98 (11.2%), continuity correction due to zero event.
Carvallo et al., 10/19/2020, prospective, Argentina, South America, preprint, 1 author, dosage 1mg days 1-14, this trial uses multiple treatments in the treatment arm (combined with iota-carrageenan) - results of individual treatments may vary.
Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats
Details
Study showing that nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats. Authors note that additional experiments are required to assess the safety of this formulation in larger animals.
Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats
Study showing that nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats. Authors note that additional experiments are required to assess the safety of this formulation in larger animals.
Chaccour et al., 10/13/2020, peer-reviewed, 8 authors.
Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID-19 (ICON study)
Retrospective 280 hospitalized patients showing lower mortality with ivermectin (13.3% vs 24.5%), propensity matched odds ratio OR 0.47 [0.22-0.99], p=0.045.
risk of death, 46.0% lower, RR 0.54, p = 0.04, treatment 13 of 98 (13.3%), control 24 of 98 (24.5%), adjusted, OR converted to RR, PSM.
risk of death, 66.9% lower, RR 0.33, p = 0.03, treatment 26 of 173 (15.0%), control 27 of 107 (25.2%), adjusted, OR converted to RR, multivariate.
risk of mechanical ventilation, 63.6% lower, RR 0.36, p = 0.10, treatment 4 of 98 (4.1%), control 11 of 98 (11.2%), matched cohort excluding intubated at baseline.
Rajter et al., 10/13/2020, retrospective, propensity score matching, USA, North America, peer-reviewed, 6 authors, dosage 200μg/kg single dose.
Mahmud et al., Journal of International Medical Research, doi:10.5061/dryad.qjq2bvqf6 (preprint 10/9/20) (Peer Reviewed)
death, ↓85.7%, p=0.25
Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial
Details
RCT for ivermectin+doxycycline showing improvements in mortality, recovery, progression, and virological cure. 183 treatment and 183 control patients with no deaths in the treatment arm vs. 3 in the control arm (the 3 control deaths are n..
Mahmud et al., Journal of International Medical Research, doi:10.5061/dryad.qjq2bvqf6 (preprint 10/9/20) (Peer Reviewed)
Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial
RCT for ivermectin+doxycycline showing improvements in mortality, recovery, progression, and virological cure. 183 treatment and 183 control patients with no deaths in the treatment arm vs. 3 in the control arm (the 3 control deaths are not included in the analysis of other outcomes). NCT04523831.
risk of death, 85.7% lower, RR 0.14, p = 0.25, treatment 0 of 183 (0.0%), control 3 of 183 (1.6%), continuity correction due to zero event.
risk of disease progression, 57.0% lower, RR 0.43, p < 0.001, treatment 16 of 183 (8.7%), control 32 of 180 (17.8%), adjusted, Cox regression.
risk of no recovery, 94.0% lower, RR 0.06, p < 0.001, treatment 72 of 183 (39.3%), control 100 of 180 (55.6%), adjusted, day 7, Cox regression.
risk of no recovery, 38.5% lower, RR 0.61, p = 0.005, treatment 40 of 183 (21.9%), control 64 of 180 (35.6%), day 11.
risk of no recovery, 96.0% lower, RR 0.04, p < 0.001, treatment 42 of 183 (23.0%), control 67 of 180 (37.2%), adjusted, day 12, Cox regression.
time to recovery, 27.0% lower, RR 0.73, p = 0.003, treatment 183, control 180, Cox regression.
risk of no virological cure, 39.0% lower, RR 0.61, p = 0.002, treatment 14 of 183 (7.7%), control 36 of 180 (20.0%), adjusted, Cox regression.
Mahmud et al., 10/9/2020, Double Blind Randomized Controlled Trial, Bangladesh, South Asia, peer-reviewed, 15 authors, dosage 12mg single dose, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.
Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru
Details
Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care.
This study includes anyone with ICD-10..
Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru
Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care.This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication.In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group.For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More than the total excess mortality happened on the first day. This is consistent with treated patients being in more serious condition, and with many of the control group patients being in hospital for something unrelated to COVID-19.Authors use a machine learning based propensity scoring system that appears over-parameterized and likely to result in significant overfitting and inaccurate results. Essentially they test for all interactions between two and three covariates. The nature and large number of covariates means many random correlations may be found. COVID-19 severity is not used.This study also does not compare treatments with a control group not receiving the treatment - authors put patients receiving treatments after 48 hours in the control group.Authors state that outcomes within 24 hours were excluded, however KM curves show significant mortality at day 1 (only for the treatment groups).Several protocol violations and missing data have also been reported in this study: [1, 2].See also: [3].Ivermectin dosage details: [4]
risk of death, 17.1% lower, RR 0.83, p = 0.01, treatment 92 of 203 (45.3%), control 1438 of 2630 (54.7%), IVM vs. control day 43 (last day available) weighted KM from figure 3, per the pre-specified rules, the last available day mortality results have priority.
risk of death, 39.0% higher, RR 1.39, p = 0.16, treatment 47 of 203 (23.2%), control 401 of 2630 (15.2%), adjusted, day 30, Table 2, IVM wHR.
Soto-Becerra et al., 10/8/2020, retrospective, database analysis, Peru, South America, preprint, median age 59.4, 4 authors, dosage 200μg/kg single dose.
Chachar et al., International Journal of Sciences, 9:31-35, doi:10.18483/ijSci.2378 (Peer Reviewed)
Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients
Small RCT with 25 ivermectin and 25 control patients, not finding a significant difference in recovery at day 7.
risk of no recovery at day 7, 10.0% lower, RR 0.90, p = 0.50, treatment 9 of 25 (36.0%), control 10 of 25 (40.0%).
Chachar et al., 9/30/2020, Randomized Controlled Trial, India, South Asia, peer-reviewed, 6 authors, dosage 36mg, 12mg stat, 12mg after 12 hours, 12mg after 24 hours.
Ivermectin treatment may improve the prognosis of patients with COVID-19
Details
Retrospective 115 ivermectin patients and 133 control patients showing significantly lower death and faster viral clearance. Some potential issues and the authors' response can be found in [1, 2].
Ivermectin treatment may improve the prognosis of patients with COVID-19
Retrospective 115 ivermectin patients and 133 control patients showing significantly lower death and faster viral clearance. Some potential issues and the authors' response can be found in [1, 2].
Quantitative proteomics reveals a broad‐spectrum antiviral property of ivermectin, benefiting for COVID‐19 treatment
DetailsIn Vitro study showing Ivermectin is a safe wide-spectrum antiviral against SARS-CoV-2, human papillomavirus (HPV), Epstein–Barr virus (EBV), and HIV.
Authors note that the combination of ivermectin and other drugs might result in more f..
Quantitative proteomics reveals a broad‐spectrum antiviral property of ivermectin, benefiting for COVID‐19 treatment
In Vitro study showing Ivermectin is a safe wide-spectrum antiviral against SARS-CoV-2, human papillomavirus (HPV), Epstein–Barr virus (EBV), and HIV.Authors note that the combination of ivermectin and other drugs might result in more favorable prognoses for patients with COVID‐19, for example ivermerctin and HCQ.
Li et al., 9/22/2020, peer-reviewed, 3 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Carvallo et al., Journal of Clinical Trials, 11:459 (preprint 9/15/20) (Peer Reviewed)
death, ↓85.4%, p=0.08
Safety and Efficacy of the Combined Use of Ivermectin, Dexamethasone, Enoxaparin and Aspirina against COVID-19 the I.D.E.A. Protocol
Details
Prospective trial of ivermectin, dexamethasone, enoxaparin, and aspirin, showing no hospitalization for mild cases, and lower mortality for moderate/severe patients.
Carvallo et al., Journal of Clinical Trials, 11:459 (preprint 9/15/20) (Peer Reviewed)
Safety and Efficacy of the Combined Use of Ivermectin, Dexamethasone, Enoxaparin and Aspirina against COVID-19 the I.D.E.A. Protocol
Prospective trial of ivermectin, dexamethasone, enoxaparin, and aspirin, showing no hospitalization for mild cases, and lower mortality for moderate/severe patients.
moderate/severe patients, 85.4% lower, RR 0.15, p = 0.08, treatment 1 of 32 (3.1%), control 3 of 14 (21.4%), the only treatment death was a patient already in the ICU before treatment.
Carvallo et al., 9/15/2020, prospective, Argentina, South America, peer-reviewed, mean age 55.7, 3 authors, dosage 36mg days 1, 8, dose varied depending on patient condition - mild 24mg, moderate 36mg, severe 48mg, this trial uses multiple treatments in the treatment arm (combined with dexamethasone, enoxaparin, and aspirin) - results of individual treatments may vary.
Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?
Details
Review of ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2.
Cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, V..
Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?
Review of ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2.Cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19).
Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies
DetailsIn Silico study showing high binding affinity of ivermectin with SARS-CoV-2 RNA-dependent RNA polymerase, suggesting ivermectin as an inhibitor of RdRp.
Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies
In Silico study showing high binding affinity of ivermectin with SARS-CoV-2 RNA-dependent RNA polymerase, suggesting ivermectin as an inhibitor of RdRp.
Swargiary et al., 9/9/2020, preprint, 1 author.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19
Details
Review suggesting that ivermectin may be useful for late stage COVID-19. Authors note that ivermectin, in doses at or modestly above the standard clinical dose, may have important clinical potential for managing disorders associated with ..
Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19
Review suggesting that ivermectin may be useful for late stage COVID-19. Authors note that ivermectin, in doses at or modestly above the standard clinical dose, may have important clinical potential for managing disorders associated with life-threatening respiratory distress and cytokine storm, such as advanced COVID-19.
DiNicolantonio et al., 9/6/2020, peer-reviewed, 3 authors.
Podder et al., IMC J. Med. Science, 14:2, July 2020 (Peer Reviewed)
recov. time, ↓16.1%, p=0.34
Outcome of ivermectin treated mild to moderate COVID-19 cases: a single-centre, open-label, randomised controlled study
Details
Small RCT with 32 ivermectin patients and 30 control patients. The mean recovery time after enrolment in the intervention arm was 5.31 ± 2.48 days vs. 6.33 ± 4.23 days in the control arm, p > 0.05. Negative PCR results were not significan..
Podder et al., IMC J. Med. Science, 14:2, July 2020 (Peer Reviewed)
Outcome of ivermectin treated mild to moderate COVID-19 cases: a single-centre, open-label, randomised controlled study
Small RCT with 32 ivermectin patients and 30 control patients. The mean recovery time after enrolment in the intervention arm was 5.31 ± 2.48 days vs. 6.33 ± 4.23 days in the control arm, p > 0.05. Negative PCR results were not significantly different between control and intervention arms, p>0.05. We are not sure what the results were because the abstract and Table 5 have switched the results.
recovery time from enrollment, 16.1% lower, relative time 0.84, p = 0.34, treatment 32, control 30.
Podder et al., 9/3/2020, Randomized Controlled Trial, Bangladesh, South Asia, peer-reviewed, 4 authors, dosage 200μg/kg single dose.
Ivermectin as adjuvant to hydroxychloroquine in patients resistant to standard treatment for SARS-CoV-2: results of an open-label randomized clinical study
Details
Small RCT of hospitalized patients in India with 19 ivermectin patients and 13 control patients, with all receiving SOC including HCQ, showing no significant differences. The patient population is biased because the study recruited patien..
Ivermectin as adjuvant to hydroxychloroquine in patients resistant to standard treatment for SARS-CoV-2: results of an open-label randomized clinical study
Small RCT of hospitalized patients in India with 19 ivermectin patients and 13 control patients, with all receiving SOC including HCQ, showing no significant differences. The patient population is biased because the study recruited patients that did not respond to standard treatment. Authors do not specify the treatment delay but it is likely relatively late because the patients had already undergone standard treatment. Criteria for discharge are not provided. The time of discharge status is not specified and may not have been an equal time since treatment initiation for all patients.Authors indicate 19 treatment and 16 control patients, but the results only show 13 control patients. Authors do not indicate why the other 3 are missing.Randomization in this small sample resulted in very large differences in the groups, with over twice as many in the ivermectin group with age >40, and the only 2 patients with age >60 both in the ivermectin group. Authors did not adjust for these differences.
risk of no hospital discharge, 7.5% higher, RR 1.08, p = 1.00, treatment 11 of 19 (57.9%), control 7 of 13 (53.8%).
risk of no virological cure, 7.5% higher, RR 1.08, p = 1.00, treatment 11 of 19 (57.9%), control 7 of 13 (53.8%), day 3.
risk of no virological cure, 220.0% higher, RR 3.20, p = 0.45, treatment 1 of 5 (20.0%), control 0 of 6 (0.0%), continuity correction due to zero event, day 5.
Kishoria et al., 8/31/2020, Randomized Controlled Trial, India, South Asia, peer-reviewed, 7 authors, dosage 12mg single dose.
Use of Ivermectin as a Potential Chemoprophylaxis for COVID-19 in Egypt: A Randomised Clinical Trial
Details
PEP trial for asymptomatic close contacts of COVID-19 patients, 203 ivermectin patients and 101 control patients. 7.4% of contacts developed COVID-19 in the ivermectin group vs. 58.4% in the control group, adjusted odds ratio OR 0.087, p ..
Use of Ivermectin as a Potential Chemoprophylaxis for COVID-19 in Egypt: A Randomised Clinical Trial
PEP trial for asymptomatic close contacts of COVID-19 patients, 203 ivermectin patients and 101 control patients. 7.4% of contacts developed COVID-19 in the ivermectin group vs. 58.4% in the control group, adjusted odds ratio OR 0.087, p < 0.001. NCT04422561. See also [1].
Espitia-Hernandez et al., Biomedical Research, 31:5 (Peer Reviewed)
recov. time, ↓70.0%, p<0.0001
Effects of Ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study
Details
Small study with 28 patients treated with ivermectin + AZ + cholecalciferol and 7 control patients.
All treated patients were PCR- at day 10 while all control patients remained PCR+. The mean duration of symptoms was 3 days in the treatm..
Espitia-Hernandez et al., Biomedical Research, 31:5 (Peer Reviewed)
Effects of Ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study
Small study with 28 patients treated with ivermectin + AZ + cholecalciferol and 7 control patients.All treated patients were PCR- at day 10 while all control patients remained PCR+. The mean duration of symptoms was 3 days in the treatment group and 10 days in the control group.
recovery time, 70.0% lower, relative time 0.30, p < 0.001, treatment 28, control 7.
risk of viral+ at day 10, 97.2% lower, RR 0.03, p < 0.001, treatment 0 of 28 (0.0%), control 7 of 7 (100.0%), continuity correction due to zero event.
Espitia-Hernandez et al., 8/15/2020, retrospective, Mexico, North America, peer-reviewed, mean age 45.1, 5 authors, dosage 6mg days 1-2, 8-9, this trial uses multiple treatments in the treatment arm (combined with azithromycin and cholecalciferol) - results of individual treatments may vary.
Observational Study on Clinical Features, Treatment and Outcome of COVID 19 in a tertiary care Centre in India- a retrospective case series
Details
Retrospective 148 hospitalized patients showing triple therapy with ivermectin + atorvastatin + N-acetylcysteine resulted in a 1.35% case fatality rate which was well below the national average.
Observational Study on Clinical Features, Treatment and Outcome of COVID 19 in a tertiary care Centre in India- a retrospective case series
Retrospective 148 hospitalized patients showing triple therapy with ivermectin + atorvastatin + N-acetylcysteine resulted in a 1.35% case fatality rate which was well below the national average.
Bhattacharya et al., 8/14/2020, peer-reviewed, mean age 57.6, 6 authors.
White paper on Ivermectin as a potential therapy for COVID-19
Details
Panel review of ivermectin reporting that "ivermectin in the dose of 12mg BD alone or in combination with other therapy for 5–7 days may be considered as safe therapeutic option for mild moderate or severe cases of Covid-19 infection..
White paper on Ivermectin as a potential therapy for COVID-19
Panel review of ivermectin reporting that "ivermectin in the dose of 12mg BD alone or in combination with other therapy for 5–7 days may be considered as safe therapeutic option for mild moderate or severe cases of Covid-19 infection. It is cost effective especially when the other drugs are very costly & not easily available".
Rahman et al., J. Bangladesh Coll. Phys. Surg. 38, 5-9, doi:10.3329/jbcps.v38i0 (Peer Reviewed)
Comparison of Viral Clearance between Ivermectin with Doxycycline and Hydroxychloroquine with Azithromycin in COVID-19 Patients
Details
Comparison of 200 patients treated with ivermectin + doxycycline and 200 treated with HCQ + AZ. The HCQ + AZ group had more severe cases at baseline. Viral clearance was faster with ivermectin + doxycycline, however ivermectin clearance r..
Rahman et al., J. Bangladesh Coll. Phys. Surg. 38, 5-9, doi:10.3329/jbcps.v38i0 (Peer Reviewed)
Comparison of Viral Clearance between Ivermectin with Doxycycline and Hydroxychloroquine with Azithromycin in COVID-19 Patients
Comparison of 200 patients treated with ivermectin + doxycycline and 200 treated with HCQ + AZ. The HCQ + AZ group had more severe cases at baseline. Viral clearance was faster with ivermectin + doxycycline, however ivermectin clearance results are only shown for days 5 and 6 and HCQ+AZ results are only shown for days 11 and 12. Results are unadjusted for differences between the groups.
Rahman et al., 7/31/2020, peer-reviewed, 6 authors.
A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients
Details
Small 116 patient RCT with low-risk patients comparing ivermectin+doxycycline and HCQ+AZ, showing lower hospitalization, higher viral clearance, and faster symptom resolution and viral clearance with ivermectin+doxycycline. Mid-recovery r..
A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients
Small 116 patient RCT with low-risk patients comparing ivermectin+doxycycline and HCQ+AZ, showing lower hospitalization, higher viral clearance, and faster symptom resolution and viral clearance with ivermectin+doxycycline. Mid-recovery resolution of symptoms is statistically significantly better with treatment, while other measures do not reach statistical significance. Instructions were to take ivermectin on an empty stomach, reducing lung tissue concentration. NCT04434144.
risk of hospitalization, 80.6% lower, RR 0.19, p = 0.23, treatment 0 of 60 (0.0%), control 2 of 56 (3.6%), continuity correction due to zero event.
risk of no recovery, 46.4% lower, RR 0.54, p < 0.001, treatment 27 of 60 (45.0%), control 47 of 56 (83.9%), mid-recovery day 5.
recovery time, 15.2% lower, relative time 0.85, p = 0.07, treatment 60, control 56.
risk of no virological cure, 80.6% lower, RR 0.19, p = 0.23, treatment 0 of 60 (0.0%), control 2 of 56 (3.6%), continuity correction due to zero event.
time to viral-, 4.3% lower, relative time 0.96, p = 0.23, treatment 60, control 56.
Chowdhury et al., 7/14/2020, Randomized Controlled Trial, Bangladesh, South Asia, peer-reviewed, 6 authors, dosage 200μg/kg single dose, this trial compares with another treatment - results may be better when compared to placebo, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.
Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial)
Details
Small trial of hospitalized patients with 16 of 87 patients being treated with ivermectin, showing a significantly lower mean hospital stay with ivermectin: 7.62 vs. 13.22 days, p=0.00005. 0 of 16 ivermectin patients died vs. 2 of 71 cont..
Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial)
Small trial of hospitalized patients with 16 of 87 patients being treated with ivermectin, showing a significantly lower mean hospital stay with ivermectin: 7.62 vs. 13.22 days, p=0.00005. 0 of 16 ivermectin patients died vs. 2 of 71 control patients.
risk of death, 71.0% lower, RR 0.29, p = 1.00, treatment 0 of 16 (0.0%), control 2 of 71 (2.8%), continuity correction due to zero event.
hospitalization time, 42.0% lower, relative time 0.58, p < 0.001, treatment 16, control 71.
risk of no recovery, 71.0% lower, RR 0.29, p = 1.00, treatment 0 of 16 (0.0%), control 2 of 71 (2.8%), continuity correction due to zero event.
Gorial et al., 7/8/2020, retrospective, Iraq, Middle East, preprint, 9 authors, dosage 200μg/kg single dose.
Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen
Details
Review of the antimicrobial, antiviral, and anti-cancer properties of ivermectin.
Antiviral effects have been reported for Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki For..
Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen
Review of the antimicrobial, antiviral, and anti-cancer properties of ivermectin.Antiviral effects have been reported for Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2. Ivermectin plays a role in several biological mechanisms, therefore it could serve as a potential candidate in the treatment of a wide range of viruses including COVID-19 as well as other types of positive-sense single-stranded RNA viruses. In vivo studies of animal models revealed a broad range of antiviral effects of ivermectin, however, clinical trials are necessary to appraise the potential efficacy of ivermectin in clinical setting.
Heidary et al., 6/12/2020, peer-reviewed, 2 authors.
Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics
Details
Pharmacokinetic analysis predicting that ivermectin will achieve lung concentration over 10 times higher than the reported EC50.
Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics
Pharmacokinetic analysis predicting that ivermectin will achieve lung concentration over 10 times higher than the reported EC50.
Arshad et al., 5/20/2020, peer-reviewed, 22 authors.
Inclusión de la ivermectina en la primera línea de acción terapéutica para COVID-19
Details
Peru observational case study of 7 patients treated with ivermectin, showing improvement and resolution of fever within 48 hours, and 100% recovery.
Ivermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses
Details
Responses to Caly et al., and the author's reply. The original authors note that "ivermectin's key direct target in mammalian cells is a not a viral component, but a host protein important in intracellular transport; the fact that it..
Ivermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses
Responses to Caly et al., and the author's reply. The original authors note that "ivermectin's key direct target in mammalian cells is a not a viral component, but a host protein important in intracellular transport; the fact that it is a host-directed agent (HDA) is almost certainly the basis of its broad-spectrum activity against a number of different RNA viruses in vitro. The way a HDA can reduce viral load is by inhibiting a key cellular process that the virus hijacks to enhance infection by suppressing the host antiviral response. Reducing viral load by even a modest amount by using a HDA at low dose early in infection can be the key to enabling the body's immune system to begin to mount the full antiviral response before the infection takes control."
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro
DetailsIn Vitro study showing that ivermectin is an inhibitor of SARS-CoV-2, with a single addition to Vero-hSLAM cells 2h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48h.
Some people claim this study show..
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro
In Vitro study showing that ivermectin is an inhibitor of SARS-CoV-2, with a single addition to Vero-hSLAM cells 2h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48h.Some people claim this study shows that therapeutic concentrations cannot be reached in humans, however this is incorrect. The authors explain why using this in vitro study to determine the effective dose in vivo is a fallacy in this presentation [1]. Authors indicate that the concentration required is very unlikely to be an issue. The study used monkey kidney cells (the only choice at the time of the experiments), which they note lack adaptive immune responses and do not produce interferon. Authors also note that ivermectin accumulates in lung and other tissues, and that the average lung concentration shown in modeling studies exceeds the effective level in their study. Authors have also repeated experiments with human lung cells showing 6-8 times improved IC50.Author's have also responded noting that "ivermectin's key direct target in mammalian cells is a not a viral component, but a host protein important in intracellular transport; the fact that it is a host-directed agent (HDA) is almost certainly the basis of its broad-spectrum activity against a number of different RNA viruses in vitro. The way a HDA can reduce viral load is by inhibiting a key cellular process that the virus hijacks to enhance infection by suppressing the host antiviral response. Reducing viral load by even a modest amount by using a HDA at low dose early in infection can be the key to enabling the body's immune system to begin to mount the full antiviral response before the infection takes control." Authors note that ivermectin works with the immune system and a 1:1 ratio of drug to virus is unlikely to be required [2].In further research, authors note that they find efficacy for prophylactic use, and that smaller repeated doses is more efffective than a single larger dose [3].Rajter et al. summarize the author, noting that “the antiviral activities of ivermectin have been derived from laboratory experiments that largely involve high, generally non physiologic, multiplicities of infection, and cell mono layer cultures, often of cell lines such as Vero cells that are not clinically relevant. The EC50 values should not be interpreted beyond the fact that they reveal robust, dose dependent antiviral activity in the cell model system used, and it would be naive to strive for μM concentrations of ivermectin in the clinic based on them.” [4].
Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects
Details
Safety study concluding that ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-approved dose. Adverse effects were similar between ivermectin and placebo and di..
Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects
Safety study concluding that ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-approved dose. Adverse effects were similar between ivermectin and placebo and did not increase with dose. Authors also show that the plasma concentration is much higher when taken with food (geometric mean AUC 2.6 times higher).
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