Abstract: ## CLINICAL INVESTIGATION
Ivermectin for Critically and Noncritically Ill Hospitalized Patients With COVID-19: Randomized, Embedded, Multifactorial Adaptive Platform Trial for CommunityAcquired Pneumonia (REMAP-CAP)
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: adaptive platform trial; antiviral; COVID-19; intensive care; ivermectin; pneumonia
Madiha Hashmi, MD 1
Rashan Haniffa, PhD 2,3
Deva Jayakumar, MS, MSc 4
Abigail Beane, PhD 2,3
Elizabeth Lorenzi, PhD 5
Lindsay R. Berry, PhD 5
Muhammad Nasir Khoso, MBBS 6
Quratul Ain Khan, MD 7
Ashok Kumar, FCPS 8
Aneela Altaf Kidwai, FCPS 9
Thomas E. Hills, MBBS, PhD 10
Djillali Annane, MD, PhD 11
Diptesh Aryal, MD, PhD 12
Carly Au, BSc 13
Kenneth Baillie, MBChB, PhD 14
Richard Beasley, MBChB, MD 10
Janis Best-Lane, BSc 15
Marc Bonten, MD, PhD 16,17
Charlotte A. Bradbury, MD, PhD 18
Copyright © 2026 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons AttributionNon Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way ..
DOI record:
{
"DOI": "10.1097/ccm.0000000000007134",
"ISSN": [
"0090-3493",
"1530-0293"
],
"URL": "http://dx.doi.org/10.1097/CCM.0000000000007134",
"abstract": "<jats:sec>\n <jats:title>Objective:</jats:title>\n <jats:p>To determine whether ivermectin improves outcomes for critically and noncritically ill hospitalized patients with COVID-19.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Design:</jats:title>\n <jats:p>An ongoing international, multifactorial, adaptive platform, randomized, controlled trial.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Setting:</jats:title>\n <jats:p>Hospitals in Pakistan, India, and Ireland between June 11, 2021, and September 9, 2022.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Patients:</jats:title>\n <jats:p>Critically and noncritically ill patients.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Interventions:</jats:title>\n <jats:p>Randomized to ivermectin or no ivermectin (control).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Measurements and Main Results:</jats:title>\n <jats:p>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%.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions:</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>",
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