Ivermectin for Critically and Noncritically Ill Hospitalized Patients With COVID-19: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP)

Abstract

Objective: To determine whether ivermectin improves outcomes for critically and noncritically ill hospitalized patients with COVID-19.

Design: An ongoing international, multifactorial, adaptive platform, randomized, controlled trial.

Setting: Hospitals in Pakistan, India, and Ireland between June 11, 2021, and September 9, 2022.

Patients: Critically and noncritically ill patients.

Interventions: Randomized to ivermectin or no ivermectin (control).

Measurements and main results: The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors. Analyses used a Bayesian cumulative logistic model. Enrollment was closed for operational futility, following external evidence suggesting no benefit with ivermectin in nonhospitalized patients with COVID-19. Among 61 critically ill patients, the median number of organ support-free days was -1, indicating death was the most common vital outcome (interquartile range [IQR], -1 to 17), for the ivermectin group and -1 (IQR, -1 to 17.25) for the control group (adjusted proportional odds ratio [OR], 0.94; 95% credible interval [CrI], 0.40-2.07) and the posterior probability of superiority to control was 44.2%. Among 89 noncritically ill patients, the median number of organ support-free days was 22 (IQR, 18.5-22) for ivermectin and 22 (IQR, 16-22) for control (adjusted proportional OR, 1.04; 95% CrI, 0.48-2.34) and the posterior probability of superiority was 53.7%. Among critically ill patients, hospital survival was 35.1% (13/37) for ivermectin and 37.5% (9/24) for control (adjusted OR, 1.00; 95% CrI, 0.39-2.32), posterior probability of superiority was 50.0%. Among noncritically ill patients, hospital survival was 84.1% (37/44) for ivermectin and 77.8% (35/45) for control (adjusted OR, 1.16; 95% CrI, 0.5-3.07), posterior probability of superiority was 63.3%.

Conclusions: For critically and noncritically ill hospitalized patients with COVID-19, ivermectin was unlikely to improve the primary composite outcome of organ support-free days and hospital survival.

Keywords: COVID-19; adaptive platform trial; antiviral; intensive care; ivermectin; pneumonia.