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, Thomas G. Stewart, Alex J. Slandzicki, Stephen C. Lim, Jonathan Cohen, David Kavtaradze, Arch P. Amon, Ahab Gabriel, Nina Gentile, G. Michael Felker, Dushyantha Jayaweera, Matthew W. McCarthy, Mark Sulkowski, Russell L. Rothman, Sybil Wilson, Allison Delong, April Remaly, Rhonda WilderSean Collins, Sarah E. Dunsmore, Stacey J. Adam, Florence Thicklin, George J. Hanna, Adit A. Ginde, Mario Castro, Kathleen McTigue, Elizabeth Shenkman, Adrian F. Hernandez

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)888-897
Number of pages10
JournalJAMA
Volume329
Issue number11
DOIs
StatePublished - Mar 21 2023

Bibliographical note

Publisher Copyright:
© 2023 American Medical Association. All rights reserved.

Fingerprint

Dive into the research topics of 'Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: A Randomized Clinical Trial'. Together they form a unique fingerprint.

Cite this