Effect of Antiplatelet Therapy on Survival and Organ Support Free Days in Critically Ill Patients with COVID-19: A Randomized Clinical Trial: REMAP-CAP COVID-19 Antiplatelet Domain RCT

Research output: Working paper


IMPORTANCE The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain.
OBJECTIVE To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19.
DESIGN, SETTING AND PARTICIPANTS In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19, were enrolled between October 30th 2020 and June 23rd 2021 from 105 sites in 8 countries and followed for 90 days (final follow up date July 26, 2021).
INTERVENTIONS Patients were randomized to either open-label aspirin (n=565), P2Y12 inhibitor (n=455), or no antiplatelet therapy (control, n=529). Interventions were continued in hospital for 14 days maximum and were in addition to anticoagulation thromboprophylaxis.
MAIN OUTCOMES AND MEASURES The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular organ support, OSFDs) within 21 days, ranging from -1 for any death in hospital (censored at 90 days), to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a Bayesian cumulative logistic model. An odds ratio (OR)>1 represented improved survival, more OSFDs, or both. Efficacy was defined as >99% posterior probability of an OR>1. Futility was defined as a >95% posterior probability of an OR<1.2 compared with control. Intervention equivalence was defined as >90% probability the OR (compared with each other) was between 1/1.2 and 1.2 for two non-control interventions.
RESULTS The aspirin and P2Y12 inhibitor groups met the pre-defined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the pre-specified criterion for futility was met for pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). Median(IQR) OSFDs was 7(-1, 16) in both antiplatelet and control groups (median adjusted OR 1.02(95%Crl: 0.86, 1.23); 95.7% posterior probability of futility). The proportion of patients surviving to hospital discharge was 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups (median adjusted OR 1.27 (95%Crl: 0.99, 1.62); adjusted absolute difference 5% (95%CrI: -0.2, 9.5), 97% posterior probability of efficacy). Among survivors, median OSFDs was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR 2.97 (95%CrI: 1.23, 8.28), adjusted absolute risk increase 0.8% (95%CrI: 0.1%, 2.7%), 99.4% probability of harm).
CONCLUSIONS AND RELEVANCE Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days.
TRIAL REGISTRATION ClinicalTrials.gov number:NCT02735707
Original languageEnglish
Publication statusPublished - 31 Mar 2022


  • Adaptive platform trial; randomized controlled trial; intensive care, pneumonia; COVID-19; antiplatelet; aspirin; clopidogrel


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