1. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.
- Author
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Bradbury C.A., Lawler P.R., Stanworth S.J., McVerry B.J., McQuilten Z., Higgins A.M., Mouncey P.R., Al-Beidh F., Rowan K.M., Berry L.R., Lorenzi E., Zarychanski R., Arabi Y.M., Annane D., Beane A., van Bentum-Puijk W., Bhimani Z., Bihari S., Bonten M.J.M., Brunkhorst F.M., Buzgau A., Buxton M., Carrier M., Cheng A.C., Cove M., Detry M.A., Estcourt L.J., Fitzgerald M., Girard T.D., Goligher E.C., Goossens H., Haniffa R., Hills T., Huang D.T., Horvat C.M., Hunt B.J., Ichihara N., Lamontagne F., Leavis H.L., Linstrum K.M., Litton E., Marshall J.C., McAuley D.F., McGlothlin A., McGuinness S.P., Middeldorp S., Montgomery S.K., Morpeth S.C., Murthy S., Neal M.D., Nichol A.D., Parke R.L., Parker J.C., Reyes L., Saito H., Santos M.S., Saunders C.T., Serpa-Neto A., Seymour C.W., Shankar-Hari M., Singh V., Tolppa T., Turgeon A.F., Turner A.M., van de Veerdonk F.L., Green C., Lewis R.J., Angus D.C., McArthur C.J., Berry S., Derde L.P.G., Webb S.A., Gordon A.C., Bradbury C.A., Lawler P.R., Stanworth S.J., McVerry B.J., McQuilten Z., Higgins A.M., Mouncey P.R., Al-Beidh F., Rowan K.M., Berry L.R., Lorenzi E., Zarychanski R., Arabi Y.M., Annane D., Beane A., van Bentum-Puijk W., Bhimani Z., Bihari S., Bonten M.J.M., Brunkhorst F.M., Buzgau A., Buxton M., Carrier M., Cheng A.C., Cove M., Detry M.A., Estcourt L.J., Fitzgerald M., Girard T.D., Goligher E.C., Goossens H., Haniffa R., Hills T., Huang D.T., Horvat C.M., Hunt B.J., Ichihara N., Lamontagne F., Leavis H.L., Linstrum K.M., Litton E., Marshall J.C., McAuley D.F., McGlothlin A., McGuinness S.P., Middeldorp S., Montgomery S.K., Morpeth S.C., Murthy S., Neal M.D., Nichol A.D., Parke R.L., Parker J.C., Reyes L., Saito H., Santos M.S., Saunders C.T., Serpa-Neto A., Seymour C.W., Shankar-Hari M., Singh V., Tolppa T., Turgeon A.F., Turner A.M., van de Veerdonk F.L., Green C., Lewis R.J., Angus D.C., McArthur C.J., Berry S., Derde L.P.G., Webb S.A., and Gordon A.C.
- Abstract
Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective(s): To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participant(s): 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 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Intervention(s): Patients were randomized to receive either open-label aspirin (n=565), a P2Y12 inhibitor (n=455), or no antiplatelet therapy (control; n=529). Interventions were continued in the hospital for a maximum of 14 days 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 intensive care unit-based respiratory or cardiovascular organ support) 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) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Result(s): The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecifie
- Published
- 2022