Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial

Susanna Naggie, David R. Boulware, Christopher J. Lindsell, Thomas G. Stewart, Nina Gentile, Sean Collins, Matthew William McCarthy, Dushyantha Jayaweera, Mario Castro, Mark Sulkowski, Kathleen McTigue, Florence Thicklin, G. Michael Felker, Adit A. Ginde, Carolyn T. Bramante, Alex J. Slandzicki, Ahab Gabriel, Nirav S. Shah, Leslie A. Lenert, Sarah E. DunsmoreStacey J. Adam, Allison Delong, George Hanna, April Remaly, Rhonda Wilder, Sybil Wilson, Elizabeth Shenkman, Adrian F. Hernandez

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Importance: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. Objective: To evaluate the efficacy of ivermectin, 400 μg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Interventions: Participants were randomized to receive ivermectin, 400 μg/kg (n = 817), daily for 3 days or placebo (n = 774). Main Outcomes and Measures: Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Results: Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] =.91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to 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)1595-1603
Number of pages9
JournalJAMA
Volume328
Issue number16
DOIs
StatePublished - Oct 25 2022

Bibliographical note

Funding Information:
process funded by the NIH. [16] The PROMIS-29 consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. [17] The PROMIS-29 measures will be modified for this study and will include select questions from each of the seven health domains, refer to the MOP for details.

Funding Information:
Funding/Support: ACTIV-6 is funded by NCATS (3U24TR001608-05W1) and the Vanderbilt University Medical Center Recruitment Innovation Core (U24TR001579). Additional support for this study was provided by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (contract No.75A50122C00037). The Vanderbilt University Medical Center Clinical and Translational Science Award from NCATS (UL1TR002243) supported the REDCap infrastructure.

Funding Information:
reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study and grants from Gilead Sciences and AbbVie; personal fees from Pardes Biosciences, Personal

Publisher Copyright:
© 2022 American Medical Association. All rights reserved.

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