Ivermectin for Critically and Noncritically Ill Hospitalized Patients With COVID-19: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).
To determine whether ivermectin improves outcomes for critically and noncritically ill hospitalized patients with COVID-19.
An ongoing international, multifactorial, adaptive platform, randomized, controlled trial.
Hospitals in Pakistan, India, and Ireland between June 11, 2021, and September 9, 2022.
Critically and noncritically ill patients.
Randomized to ivermectin or no ivermectin (control).
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%.
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.
An ongoing international, multifactorial, adaptive platform, randomized, controlled trial.
Hospitals in Pakistan, India, and Ireland between June 11, 2021, and September 9, 2022.
Critically and noncritically ill patients.
Randomized to ivermectin or no ivermectin (control).
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%.
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.
Authors
Hashmi Hashmi, Haniffa Haniffa, Jayakumar Jayakumar, Beane Beane, Lorenzi Lorenzi, Berry Berry, Nasir Khoso Nasir Khoso, Ain Khan Ain Khan, Kumar Kumar, Altaf Kidwai Altaf Kidwai, Hills Hills, Annane Annane, Aryal Aryal, Au Au, Baillie Baillie, Beasley Beasley, Best-Lane Best-Lane, Bonten Bonten, Bradbury Bradbury, Brunkhorst Brunkhorst, Burrell Burrell, Buxton Buxton, Cecconi Cecconi, Cheng Cheng, Cove Cove, de Jong de Jong, Detry Detry, Duffy Duffy, Estcourt Estcourt, Fitzgerald Fitzgerald, Fowler Fowler, Goossens Goossens, Green Green, Hays Hays, Higgins Higgins, Huang Huang, Ichihara Ichihara, Koirala Koirala, Lamontagne Lamontagne, Lawler Lawler, Lewis Lewis, Litton Litton, Mahon Mahon, Marshall Marshall, McAuley McAuley, McGlothlin McGlothlin, McGuinness McGuinness, McQuilten McQuilten, McVerry McVerry, Mouncey Mouncey, Morpeth Morpeth, Netea Netea, Orr Orr, Parke Parke, Parker Parker, Patanwala Patanwala, Peters Peters, Reyes Reyes, Rowan Rowan, Saito Saito, Saunders Saunders, Santos Santos, Seymour Seymour, Shankar-Hari Shankar-Hari, Singh Singh, Slater Slater, Tambyah Tambyah, Tong Tong, Turgeon Turgeon, Turner Turner, van de Veerdonk van de Veerdonk, Weis Weis, Zarychanski Zarychanski, McArthur McArthur, Angus Angus, Berry Berry, Gordon Gordon, Derde Derde, Webb Webb, Murthy Murthy, Arabi Arabi, Nichol Nichol,
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