• Writing Committee for the REMAP-CAP Investigators, Alisa M Higgins, Lindsay R Berry, Elizabeth Lorenzi, Srinivas Murthy, Zoe McQuilten, Paul R Mouncey, Farah Al-Beidh, Djillali Annane, Yaseen M Arabi, Abi Beane, Wilma van Bentum-Puijk, Zahra Bhimani, BontenMarc J MMJMUniversity Medical Center Utrecht, Utrecht, the Netherlands., Charlotte A Bradbury, Frank M Brunkhorst, Aidan Burrell, Adrian Buzgau, Meredith Buxton, Walton N Charles, Matthew Cove, Michelle A Detry, Lise J Estcourt, Elizabeth O Fagbodun, Mark Fitzgerald, Timothy D Girard, Ewan C Goligher, Herman Goossens, Rashan Haniffa, Thomas Hills, Christopher M Horvat, David T Huang, Nao Ichihara, Francois Lamontagne, John C Marshall, Daniel F McAuley, Anna McGlothlin, Shay P McGuinness, Bryan J McVerry, Matthew D Neal, Alistair D Nichol, Rachael L Parke, Jane C Parker, Karen Parry-Billings, Sam E C Peters, Luis F Reyes, Kathryn M Rowan, Hiroki Saito, Marlene S Santos, Christina T Saunders, Ary Serpa-Neto, Christopher W Seymour, Manu Shankar-Hari, Lucy M Stronach, Alexis F Turgeon, Anne M Turner, Frank L van de Veerdonk, Ryan Zarychanski, Cameron Green, Roger J Lewis, Derek C Angus, Colin J McArthur, Scott Berry, DerdeLennie P GLPGUniversity Medical Center Utrecht, Utrecht, the Netherlands., Anthony C Gordon, Steve A Webb, and Patrick R Lawler.
• Monash University, Melbourne, Victoria, Australia.
• JAMA. 2023 Jan 3; 329 (1): 395139-51.

ImportanceThe longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.ObjectiveTo determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.Design, Setting, And ParticipantsPrespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.InterventionsPatients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).Main Outcomes And MeasuresThe main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.ResultsAmong 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.Conclusions And RelevanceAmong critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

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