Compared to placebo, ivermectin did not significantly improve time to symptom resolution in mild COVID-19 cases, according to results from a double-blind, randomized trial (ClinicalTrials.gov: NCT04405843) published in JAMA.
Mild COVID-19 patients with a median age of 37 years (interquartile range
[IQR], 29-48) were randomly assigned to receive either ivermectin or placebo at 300 μg/kg per day for 5 days. In the primary analysis, a total of 200 patients were allocated to ivermectin and 198 patients to placebo. The median time to symptom resolution in patients was 10 days for ivermectin and 12 for placebo (difference, -2 days; IQR, -4 to 2). The hazard ratio [HR] for resolution of symptoms was 1.07 (95% CI, 0.87-1.32; P =.53).
Overall, symptoms were resolved in 82% of patients in the ivermectin group and 79% of patients in the placebo group. Clinical deterioration of symptoms by 2 or more points occurred in 2% and 3.5% of patients in the ivermectin and placebo groups, respectively, and was not statistically significant. There was also no significant difference in the proportion of patients needing an escalation of care between groups.
A total of 154 patients (77%) in the ivermectin group and 161 patients (81.3%) in the placebo group reported adverse events. Of these, 15 patients (7.5%) in the ivermectin group and 5 patients (2.5%) in the placebo group discontinued treatment. Headache, which occurred in 52% of ivermectin patients and 56% of placebo patients, was the most commonly reported adverse event. The most common serious adverse event was multiorgan failure, which only occurred in 2 patients in the ivermectin group and 2 patients in the placebo group.
The original primary outcome of detecting the ability of ivermectin to prevent clinical deterioration was changed 6 weeks into the trial as the incidence of deterioration was low. The study was also limited by lack of power to detect a smaller reduction in primary endpoint, lack of virological assessments, alternative placebos used in 65 patients, a reliance on self-reporting for 2 secondary outcomes, and lack of data on ivermectin plasma levels.
According to investigators, the findings do not support ivermectin as a treatment for mild COVID19. However, investigators did acknowledge that larger trials are needed to fully understand the effects of ivermectin on other clinically relevant outcomes.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
López-Medina E, López P, Hurtado IC, et al. Effect of ivermectin on time to resolution of symptoms among adults with mild COVID-19 a randomized clinical trial. JAMA. Published online March 4, 2021. doi:10.1001/jama.2021.3071