A much-awaited ivermectin study in Argentina disappointed those looking for positive results as the IVERCOVID19 trial, sponsored by the Corrientes Institute of Cardiology “Juana F. Cabral” with funding from the Ministry of Public Health, Province of Corrientes, Argentina, came out with subpar results. The single-center, prospective, randomized, double-blind, placebo-controlled study centered on the primary endpoint as the need for hospitalization in patients with COVID-19 while secondary endpoints involved time to hospitalization in days, use of invasive mechanical ventilation, time to invasive mechanical ventilation in days, use of dialysis, and all-cause mortality. The study team acknowledged material limitations, including first that the study was underpowered but secondly and importantly the acknowledgment that the dosage was “below the doses proposed as probably effective.” Consequently, the study authors reported in the peer review journal BMC Infectious Diseases that at least in this study group, the drug had no significant effect on preventing the hospitalization of patients with COVID-19. As it turned ou,t those that did require invasive mechanical ventilation frequented the ivermectin group more while there were no discernible differences in any of the secondary endpoints. While this is overall a disappointment for ivermectin proponents, the balance of studies, as recorded in three primary meta-analyses, indicate the potential of this drug as a possible early-onset treatment. Remdesivir completely bombed in major studies to the point that the World Health Organization (WHO) recommended against any use, yet the National Institutes of Health (NIH) and U.S. Food and Drug Administration (FDA) still loyally back the drug, which has led to $3 billion of sales in the first nine months of the drug’s release. But nonetheless, the ivermectin proponents will have a more challenging time now with major economic regulatory bodies, including the one in this South American nation. The co-investigator exchanged emails with TrialSite and explained that the low dosages used in the study were primarily a function of timing and regulatory constraints. The critical point of view of another Argentinian principal investigator, Dr. Héctor Carvello, is included herein as well for what will hopefully become a dynamic dialogue worldwide.
The IVERCOVID19 study (NCT04529525) authors acknowledged considerable limitations, which included the following:
“The fact that no significant differences were found in the primary end point of hospitalizations in this study may be due to different factors. The first is that ivermectin is not effective in this group of patients to prevent hospitalizations. The second is that the IVERCORCOVID19 trial is underpowered because the hospitalization rate was lower than expected when performed in the sample size calculation, as well as the fact that an ambitious reduction of 50–70% was estimated of primary endpoint. Thirdly, the dose of ivermectin adjusted to the weight of the patients was low, which on the one hand could corroborate that these doses are not effective, but alternatively could provide the opportunity to study the efficacy of higher doses of ivermectin.”
With a mean age of study participants at 42 with a standard deviation of 15.5 years, the authors report that the median time since symptom onset to the inclusion was 4 days with an interquartile range of 3-6. When discussing the primary outcome of hospitalization while more in the placebo group (21/251) 8.4% that number was 14 out of 250 for 5.6% in the ivermectin group. According to the study odds ratio, however, 0.65; 95%, confidence interval, 0.32-1.31; p=0.227.
The time to hospitalization wasn’t statistically different while of note, the mean time from study enrollment to invasive mechanical ventilatory support was 5.25 days with a standard deviation of plus or minus 1.71 days in the ivermectin group and 10 days, with a standard deviation of plus or minus 2 in placebo group with a p value of 0.019. Other secondary endpoints are nothing of interest.