Background: To investigate the efficacy and safety of ivermectin compared to hydroxychloroquine and placebo in hospitalized moderate to severe COVID-19 patients.
Research design and methods: The study was an adaptive, randomized, double-blinded, controlled, single-center trial. The study was a series of 3-arm comparisons between two different investigational therapeutic agents (ivermectin and hydroxychloroquine) and a placebo. There was interim monitoring to allow early stopping for futility, efficacy, or safety.
Results: Ivermectin decreased survival time from 29 to 18.3 days (HR, 9.8, 95%CI, 3.7-26.2), while it did not shorten the recovery time (HR, 1.02, 95%CI, 0.69-1.5). Subgroup analysis showed an association between ivermectin-related mortality and baseline oxygen saturation level. Moreover, stratified groups showed higher risk among patients on high flow O2. Hydroxychloroquine delayed recovery from 10.1 to 12.5 days (HR, 0.62, 95%CI, 0.4-0.95) and non-significantly decreased survival time from 29 to 26.8 days (HR, 1.47, 95%CI, 0.73-2.9). However, 3 months mortality rates were increased with hydroxychloroquine (RR, 2.05, 95%CI, 1.33-3.16). Neither ivermectin nor hydroxychloroquine increased adverse events and demonstrated safety profile compared to placebo.
Conclusions: The study recommends against using either ivermectin or hydroxychloroquine for treatment of COVID-19 in hospitalized patients with any degree of severity. Clinical trial registration: www.clinicaltrials.gov identifier is: NCT04746365.
Keywords: COVID-19; clinical trial; efficacy; hydroxychloroquine; ivermectin; safety.