Ivermectin for Critically and Noncritically Ill Hospitalized Patients With COVID-19: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired 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.

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Journal
Critical Care Medicine
Published
2026-05-08
DOI
https://doi.org/10.1097/ccm.0000000000007134
Primary Topic
Parasitic Diseases Research and Treatment
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article
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article

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

Derek C. Angus, Katrina Orr, Niamh Mahon, Manu Shankar‐Hari et al.
Critical Care Medicine
Parasitic Diseases Research and Treatment
article

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

Derek C. Angus, Katrina Orr, Niamh Mahon, Manu Shankar‐Hari, David T. Huang, Nao Ichihara, Carly Au, Rashan Haniffa, Allen Cheng, Aneela Altaf Kidwai, Patrick R. Lawler, François Lamontagne, Daniel Francis McAuley, Janis Best-Lane, C. A. Bradbury, J G Marshall, Anthony C. Gordon, Sabin Koirala, Colin J. McArthur, Paul R. Mouncey, Richard Beasley, Roger Lewis, Srinivas Murthy, Vanessa Singh, Diptesh Aryal, Frank M. Brunkhorst, Muhammad Nasir Khoso, Djillali Annane, Edward Litton, Madiha Hashmi, Michelle A. Detry, Quratul Ain Khan, Thomas Hills, Ashok Kumar, Christina Saunders, Hiroki Saito, Maurizio Cecconi, Bryan J. McVerry, Anne Turner, Abigail Beane, Deva Jayakumar, Marc Bonten, Lennie P. G. Derde, Yaseen Arabi, Lise J. Estcourt, Mihai Netea, Frank van de Veerdonk, Sebastian Weis, Jane C. Parker, Rachael L. Parke, Kathryn M. Rowan, Marlene Santos, Asad Patanwala, Kenneth Baillie, Herman Goossens, Scott M. Berry, Alistair D. Nichol, Mark Fitzgerald, Lindsay R. Berry, Matthew Slater, and the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) Investigators, Steven Y. C. Tong, Svenja Peters, Steve A. Webb, Shay McGuinness, Susan Morpeth, Rob Fowler, Luis Felipe Reyes, Meredith Buxton, Zoe K. McQuilten, Anna McGlothlin, Eamon Duffy, Alexis F. Turgeon, Ryan Zarychanski, Aidan Burrell, Elizabeth Lorenzi, Alisa M. Higgins, Leanne M. C. Hays, Menno de Jong, Christopher W. Seymour, Cameron Green, Paul A. Tambyah, Matthew E. Cove
article en

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.

Critical Care Medicine
University College Dublin (IE), Queen's University Belfast (GB), Sunnybrook Health Science Centre (CA), Université de Sherbrooke (CA), University of British Columbia (CA), Radboud University Nijmegen (NL), University of Auckland (NZ), Universidad de La Sabana (CO), St. Marianna University School of Medicine (JP), The University of Melbourne (AU), National University of Singapore (SG), University of Pittsburgh (US), The University of Western Australia (AU), King Saud bin Abdulaziz University for Health Sciences (SA), University of Toronto (CA), Université de Versailles Saint-Quentin-en-Yvelines (FR), Royal Prince Alfred Hospital (AU), Middlemore Hospital (NZ), Fiona Stanley Hospital (AU), Auckland City Hospital (NZ), Belfast City Council (GB), Abbasi Shaheed Hospital (PK), The Alfred Hospital (AU), Health Sciences Centre (CA), Radboud University Medical Center (NL), University Medical Center Utrecht (NL), University of Bristol (GB), University of Oxford (GB), UPMC Health System (US), Berry & Associates (United States) (US), Peter Doherty Institute (AU), Dr. Kamakshi Memorial Hospital (IN), St. Vincent's University Hospital (IE), Infectious Diseases Institute (UG), Mahidol Oxford Tropical Medicine Research Unit (TH), Europeana Foundation (NL), VA Pittsburgh Healthcare System (US), University of Pittsburgh Medical Center (US), Jena University Hospital (DE), Medical Research Institute of New Zealand (NZ), Ziauddin Hospital (PK), Centre for Inflammation Research (GB), Intensive Care National Audit & Research Centre (GB), Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE), IRCCS Humanitas Research Hospital (IT), Alfred Health (AU), Civil Service Hospital (NP), Université Laval (CA), Sunnybrook Research Institute, Unity Health Toronto, University of Manitoba (CA), Imperial College London (GB), McGill University (CA), Monash University (AU), The University of Tokyo (JP), Friedrich Schiller University Jena (DE), Ziauddin University (PK)
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Parasitic Diseases Research and Treatment
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