RCT with 501 relatively low-risk outpatients in Argentina showing
hospitalization OR 0.65 [0.32-1.31].
With only 7% hospitalization, this 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.
The companion prophylaxis trial [Vallejos]
reported more positive results, has not yet been formally published,
suggesting a negative publication bias.
Authors pre-specify multivariate analysis but do not present
it, 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
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
). 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, knowing that they may be in the control group. Another report
states that 12,000 patients were excluded for recent use of ivermectin [scidev.net]
RCTs have a fundamental bias against finding an effect for
interventions that are widely available — patients that believe they
need treatment are more likely to decline participation and take the
, i.e., RCTs are more likely to enroll low-risk
participants that do not need treatment to recover (this does not apply to
the typical pharmaceutical trial of a new drug that is otherwise
unavailable). This trial was run in a community where ivermectin was very
widely known and used.
Vallejos et al., 7/2/2021, Double Blind Randomized Controlled Trial, Argentina, South America, peer-reviewed, 29 authors, dosage 12mg days 1-2, <80kg 12mg, 80-110kg 18mg, >110kg 24mg.
risk of death, 33.5% higher, RR 1.33, p = 0.70, treatment 4 of 250 (1.6%), control 3 of 251 (1.2%), odds ratio converted to relative risk.
risk of mechanical ventilation, 33.5% higher, RR 1.33, p = 0.70, treatment 4 of 250 (1.6%), control 3 of 251 (1.2%), odds ratio converted to relative risk.
risk of hospitalization, 33.0% lower, RR 0.67, p = 0.23, treatment 14 of 250 (5.6%), control 21 of 251 (8.4%), odds ratio converted to relative risk.
risk of no virological cure, 5.0% higher, RR 1.05, p = 0.55, treatment 137 of 250 (54.8%), control 131 of 251 (52.2%), odds ratio converted to relative risk, day 3.
risk of no virological cure, 26.8% higher, RR 1.27, p = 0.29, treatment 38 of 250 (15.2%), control 30 of 251 (12.0%), odds ratio converted to relative risk, day 12.
Effect extraction follows pre-specified rules
prioritizing more serious outcomes. For an individual study the most serious
outcome may have a smaller number of events and lower statistical signficance,
however this provides the strongest evidence for the most serious outcomes
when combining the results of many trials.