Original Investigation 

February 20, 2023

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

Susanna Naggie, David R. Boulware, Christopher J. Lindsell, et al

JAMA. Published online February 20, 2023. doi:10.1001/jama.2023.1650

Key Points

Question  Does ivermectin, with a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo, shorten symptom duration among adult (≥30 years) outpatients with symptomatic mild to moderate COVID-19?

Findings  In this double-blind, randomized, placebo-controlled platform trial including 1206 US adults with COVID-19 during February 2022 to July 2022, the median time to sustained recovery was 11 days in the ivermectin group and 11 days in the placebo group. In this largely vaccinated (84%) population, the posterior probability that ivermectin reduced symptom duration by more than 1 day was less than 0.1%.

Meaning  These findings do not support the use of ivermectin among 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 1206 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 = 602) daily, or placebo (n = 604) 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 1206 randomized participants who received study medication or placebo, the median (IQR) age was 48 (38-58) years, 713 (59.1%) were women, and 1008 (83.5%) 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 11 (11-12) days in the placebo group. The hazard ratio (posterior probability of benefit) for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.13; P = .68). Among those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (hazard ratio, 1.0 [95% credible interval, 0.6-1.5]; P = .53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 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