Database of all ivermectin COVID-19 studies. 102
studies, 67 peer reviewed, 60 with
results comparing treatment and control groups. Submit
updates/corrections below. FLCCC
provides treatment recommendations. Ivermectin related news can be found
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Ontai et al., medRxiv, doi:10.1101/2021.07.21.21260223 (Preprint)
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..
Ontai et al., medRxiv, doi:10.1101/2021.07.21.21260223 (Preprint)
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.
Ivermectin for COVID-19: real-time meta analysis of 60 studies
Details
• Meta analysis using the most serious outcome reported shows 74% and 85% improvement for early treatment and prophylaxis (RR 0.26 [0.16-0.43] and 0.15 [0.08-0.25]), with similar res..
• The probability that an ineffective treatment generated results as positive as the 60 studies to date is estimated to be 1 in 193 billion (p = 0.0000000000052).• Heterogeneity arises from many factors including treatment delay, population, effect measured, variants, and regimens. The consistency of positive results is remarkable. Heterogeneity is low in specific cases, for example early treatment mortality.• While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 30% 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.• Administration with food, often not specified, may significantly increase plasma and tissue concentration.• 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, Hill, Kory, Lawrie, Nardelli] for other meta analyses, all with similar results confirming effectiveness.
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.
Neil et al., ResearchGate, doi:0.13140/RG.2.2.31800.88323 (Preprint)
meta-analysis
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.
Neil et al., ResearchGate, doi:0.13140/RG.2.2.31800.88323 (Preprint)
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.
Hazan et al., medRxiv, doi:10.1101/2021.07.06.21259924 (Preprint)
death, ↓85.9%, p=0.04
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..
Hazan et al., medRxiv, doi:10.1101/2021.07.06.21259924 (Preprint)
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.
Vallejos et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06348-5 (Peer Reviewed)
death, ↑33.5%, p=0.70
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..
Vallejos et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06348-5 (Peer Reviewed)
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.
Turkia, M., ResearchGate, doi:10.13140/RG.2.2.16973.36326 (Review) (Preprint)
review
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..
Turkia, M., ResearchGate, doi:10.13140/RG.2.2.16973.36326 (Review) (Preprint)
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
Severely flawed meta analysis. An open letter signed by 40 physicians detailing errors and flaws, and requesting retraction, can be found at [1]. See also [2].
The authors state that they have no conflicts of interest on medRxiv, however..
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
Severely flawed meta analysis. An open letter signed by 40 physicians detailing errors and flaws, and requesting retraction, can be found at [1]. See also [2].The authors state that they have no conflicts of interest on medRxiv, however Dr. Pasupuleti’s affiliation is Cello Health, whose website [3] says 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”.Authors cherry-pick to include only 4 studies reporting non-zero mortality and they claim 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]. The correct RR for Niaee et al. is 0.18 [0.06-0.55] (as below). After correction, their cherry-picked studies show >60% mortality reduction.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). Authors actually reference meta analyses that do include the missing RCTs, so they should be aware of the missing RCTs.The PubMed search strategy provided is syntactically incorrect.For additional errors, see [4]. Also see [5].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.
Lind et al., Journal of General Internal Medicine, doi:10.1007/s11606-021-06948-6 (Review) (Peer Reviewed)
review
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.
Lind et al., Journal of General Internal Medicine, doi:10.1007/s11606-021-06948-6 (Review) (Peer Reviewed)
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.
Krolewiecki et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100959 (Peer Reviewed)
ventilation, ↑151.9%, p=1.00
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..
Krolewiecki et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100959 (Peer Reviewed)
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). NCT004381884.
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%).
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.
Aref et al., International Journal of Nanomedicine, doi:10.2147/IJN.S313093 (Peer Reviewed)
recov. time, ↓63.2%, p=0.0001
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.
Aref et al., International Journal of Nanomedicine, doi:10.2147/IJN.S313093 (Peer Reviewed)
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.
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%).
