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Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19A Randomized Clinical Trial

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To identify the key insights or developments described in this article
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Key Points

Question  What is the effect of ivermectin on duration of symptoms in adults with mild COVID-19?

Findings  In this randomized clinical trial that included 476 patients, the duration of symptoms was not significantly different for patients who received a 5-day course of ivermectin compared with placebo (median time to resolution of symptoms, 10 vs 12 days; hazard ratio for resolution of symptoms, 1.07).

Meaning  The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand effects on other clinically relevant outcomes.


Importance  Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit.

Objective  To determine whether ivermectin is an efficacious treatment for mild COVID-19.

Design, Setting, and Participants  Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state’s health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020.

Intervention  Patients were randomized to receive ivermectin, 300 μg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200).

Main Outcomes and Measures  Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected.

Results  Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group).

Conclusion and Relevance  Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.

Trial Registration  ClinicalTrials.gov Identifier: NCT04405843

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Article Information

Corresponding Author: Eduardo López-Medina, MD, MSc, Centro de Estudios en Infectología Pediátrica, Calle 5 B 5 No. 37 BIS-28, Cali, Colombia (eduardo.lopez@ceiponline.org).

Accepted for Publication: February 18, 2021.

Published Online: March 4, 2021. doi:10.1001/jama.2021.3071

Author Contributions: Drs López-Medina and Ramirez had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: López-Medina, López, Hurtado, Dávalos, Ramirez, Martínez, Díazgranados, Oñate, Chavarriaga.

Acquisition, analysis, or interpretation of data: López-Medina, Hurtado, Ramirez, Martínez, Oñate, Chavarriaga, Herrera, Parra, Libreros, Jaramillo, Avendaño, Toro, Torres, Lesmes, Rios, Caicedo.

Drafting of the manuscript: López-Medina, Hurtado, Dávalos, Chavarriaga, Caicedo.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: López-Medina, Ramirez.

Obtained funding: López-Medina, López.

Administrative, technical, or material support: Hurtado, Dávalos, Martínez, Díazgranados, Chavarriaga, Herrera, Parra, Libreros, Jaramillo, Avendaño, Toro, Torres, Lesmes, Rios, Caicedo.

Supervision: López-Medina, López, Oñate, Rios, Caicedo.

Conflict of Interest Disclosures: Dr López-Medina reported receiving grants from Sanofi Pasteur, GlaxoSmithKline, and Janssen and personal fees from Sanofi Pasteur during the conduct of the study. Dr López reported receiving grants from Sanofi Pasteur, GlaxoSmithKline, and Janssen and personal fees from Sanofi Pasteur during the conduct of the study. Dr Oñate reported receiving grants from Janssen and personal fees from Merck Sharp & Dohme and Gilead outside the submitted work. Dr Torres reported receiving nonfinancial support from Tecnoquímicas unrelated to this project during the conduct of the study. No other disclosures were reported.

Funding/Support: This study received an unrestricted grant from Centro de Estudios en Infectología Pediátrica (grant ScDi823).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: In addition to the authors, the following collaborators from Centro de Estudios en Infectología Pediátrica participated in the Estudio Para Evaluar la Ivermectina en COVID-19 (EPIC) trial:

Catalina De La Cruz, MD; Camilo Andrade; Iñigo Prieto, MD, MSc; Viviana Márquez, MD; Mary Luz Hernandez; Carlos Gonzalez, MD; Victoria Aguirre, RN; Gloria Tamayo; Leidy Gomez; Aracelly Romero; Socorro Mutis; Nidia Guaza; Eliana Valencia; James Riascos; Ovidio Maldonado; Laura Victoria, RN; Hilda Giraldo; Lina Solano, RN; Maria F. Collazos, RN; Elizabeth Toro, MD; Carlos Cortés, MD; Alexandra Sierra, MD; Carolina Ospina, MD; Diana P. Mazo, PharmD; Jhon J. Calderón; Jenny Yela, RN; Diego Rivera, RN; and Diana Suárez, PharmD.

Data Sharing Statement: See Supplement 3.

Additional Contributions: We are grateful to the patients who participated in this trial; Erika Cantor, MSc, from the Institute of Statistics, Universidad de Valparaíso, Valparaíso, Chile, for her contribution during data analysis; Keith Veitch for his writing assistance; and Neal Alexander, PhD, from CIDEIM in Cali, Colombia, and Rodrigo DeAntonio, DrPH, from Cevaxin in Panamá City, Panamá, for their contribution during study planning. Ms Cantor and Mr Veitch received compensation for their roles in the study. Drs Alexander and DeAntonio did not receive compensation for their roles in the study. We thank Tecnoquímicas for its donation of the investigational product and placebo from August 26, 2020, until the end of the trial.

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