march 2021 • JAMA

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

López-Medina E, . et al

DOI: 10.1001/jama.2021.3071

Content curated by:David Rodrigues

Key message

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 - 95% CI, 0.87 to 1.32). The findings do not support the use of ivermectin for treatment of mild COVID-19.

Analysis

Population

Adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized)

Method

Double-blind, randomized trial; Patients were randomized to receive ivermectin, 300 μg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). The primary outcome was the time from randomization to complete resolution of symptoms within the 21-day follow-up period. The 8-category ordinal scale used in this trial has been used in different COVID-19 therapeutic trials and is recommended by the World Health Organization’s R&D Blueprint. It consists of the following categories: 0 = no clinical evidence of infection; 1 = not hospitalized and no limitation of activities; 2 = not hospitalized, with limitation of activities, home oxygen requirement, or both; 3 = hospitalized, not requiring supplemental oxygen; 4 = hospitalized, requiring supplemental oxygen; 5 = hospitalized, requiring nasal high-flow oxygen, noninvasive mechanical ventilation, or both; 6 = hospitalized, requiring extracorporeal membrane oxygenation, invasive mechanical ventilation, or both; and 7 = death. Time to recovery was defined as the first day during the 21 days of follow-up in which the patient reported a score of 0.

Results

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). 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).

Abstract

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.