Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19

Abstract

Importance It is unknown whether ivermectin, with a maximum targeted dose of 600 μg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19. Objective To evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform randomized clinical trial was designed to evaluate repurposed therapies among outpatients with mild to moderate COVID-19. A total of 1432 participants older than 30 years with confirmed COVID-19 experiencing at least 2 symptoms of acute infection for less than or equal to 7 days were enrolled at 93 sites in the US from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022. Interventions Participants were randomly assigned to receive ivermectin, with a maximum targeted dose of 600 μg/kg (n = 708) daily, or placebo (n = 724) for 6 days. Main Outcomes and Measures The primary outcome was time to sustained recovery, defined as at least 3 consecutive days without symptoms. The 7 secondary outcomes included a composite of hospitalization, death, or urgent/emergent care utilization by day 28. Results Among 1432 randomized participants who received study medication or placebo, the median (IQR) age was 48 (38-58) years, 854 (59.6%) were women, and 1188 (83.1%) reported receiving at least 2 SARS-CoV-2 vaccine doses. The median (IQR) time to sustained recovery was 11 (11-12) days in the ivermectin group and 12 (11-12) days in the placebo group. The hazard ratio for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.12; P value for efficacy = .65). Among those receiving ivermectin, 39 (5.5%) were hospitalized, died, or had urgent or emergency care visits compared with 42 (5.8%) receiving placebo (hazard ratio, 0.97 [95% credible interval, 0.60-1.45]; P = .55). In the ivermectin group, 1 participant died and 6 were hospitalized (1.0%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups. Conclusions and Relevance Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo did not improve time to sustained recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration ClinicalTrials.gov Identifier: NCT04885530