On March 4, JAMA published “Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19;A Randomized Clinical Trial” by Eduardo López-Medina et al. The main finding of the study was:
“In this randomized clinical trial that included 476 patients, the duration of symptoms was not significantly different for patients who received a 5-day course of ivermectin compared with placebo…”
The authors self-reported a change to the original primary endpoint after the initiation of the study. They also acknowledged that the study was not designed to detect a difference in the hazards ratio between the intervention and the control arms of less than 1.4. Other limitations they acknowledged were the lack of virological assessment, serum plasma measurement and observable differences between the treatment drug and the placebo during a part of the trial. The authors also self-report an incident during the trial in which study participants were given the study drug instead of the placebo.
However, other questions are raised by the publication, that may be more significant:
- On page 27 and 28 of Supplement 1 attached to the publication, the final secondary outcomes of the trial are listed. One of those outcomes is “The duration of supplemental oxygen in each arm of the study.” This outcome dose not appear in Table 2 “Outcomes in the Primary Analysis Population” or in Supplement 2 attached to the publication. Why was this outcome omitted from the publication?
- The study protocol was amended 4 times. The changes to the protocol at each amendment is given on page 43 of Supplement 1 attached to the publication. The changes are listed for amendments 2–4 but not for amendment 1. Were there substantive changes to the protocol with the first amendment?
- The final title to the protocol was “Double blind, randomized, controlled clinical trial to investigate the effectiveness of the D11AX22 molecule in adult subjects from Valle Del Cauca with initial stages of infection by SARS CoV2/COVID 19.” Were the subjects in this study informed that the purpose of the trial was to determine the effectiveness of ivermectin in COVID-19?