Early terminated RCT in Brazil showing lower mortality and hospitalization with HCQ, but not reaching statistical significance. Although the title includes "early treatment", treatment was relatively late, with most patients being over 5 days from the onset of symptoms. Adverse events were lower in the HCQ group compared to the control group.
The paper indicates the placebo was talc, however the trial protocol shows the "placebo" as vitamin C, for which there are 7 COVID-19 treatment studies as of April 2021 that collectively show significant efficacy.
Reis et al., 4/22/2021, Double Blind Randomized Controlled Trial, Brazil, South America, peer-reviewed, 18 authors, dosage 800mg day 1, 400mg days 2-10.
risk of death, 66.0% lower, RR 0.34, p = 1.00, treatment 0 of 214 (0.0%), control 1 of 227 (0.4%), continuity correction due to zero event (with reciprocal of the contrasting arm).
risk of hospitalization, 24.0% lower, RR 0.76, p = 0.57, treatment 8 of 214 (3.7%), control 11 of 227 (4.8%), ITT, Cox proportional hazards.
risk of no virological cure, 4.1% lower, RR 0.96, p < 0.001, treatment 97 of 185 (52.4%), control 102 of 179 (57.0%), adjusted per study, odds ratio converted to relative risk, ITT, mixed-effect logistic model.
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.