Dataset Information

Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

ABSTRACT:

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 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).

Interventions

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.

Results

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 prespecified criterion for futility was met for the 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). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days 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 Identifier: NCT02735707.

SUBMITTER: REMAP-CAP Writing Committee for the REMAP-CAP Investigators

PROVIDER: S-EPMC8941448 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

Bradbury Charlotte A CA Lawler Patrick R PR Stanworth Simon J SJ McVerry Bryan J BJ McQuilten Zoe Z Higgins Alisa M AM Mouncey Paul R PR Al-Beidh Farah F Rowan Kathryn M KM Berry Lindsay R LR Lorenzi Elizabeth E Zarychanski Ryan R Arabi Yaseen M YM Annane Djillali D Beane Abi A van Bentum-Puijk Wilma W Bhimani Zahra Z Bihari Shailesh S Bonten Marc J M MJM Brunkhorst Frank M FM Buzgau Adrian A Buxton Meredith M Carrier Marc M Cheng Allen C AC Cove Matthew M Detry Michelle A MA Estcourt Lise J LJ Fitzgerald Mark M Girard Timothy D TD Goligher Ewan C EC Goossens Herman H Haniffa Rashan R Hills Thomas T Huang David T DT Horvat Christopher M CM Hunt Beverley J BJ Ichihara Nao N Lamontagne Francois F Leavis Helen L HL Linstrum Kelsey M KM Litton Edward E Marshall John C JC McAuley Daniel F DF McGlothlin Anna A McGuinness Shay P SP Middeldorp Saskia S Montgomery Stephanie K SK Morpeth Susan C SC Murthy Srinivas S Neal Matthew D MD Nichol Alistair D AD Parke Rachael L RL Parker Jane C JC Reyes Luis F LF Saito Hiroki H Santos Marlene S MS Saunders Christina T CT Serpa-Neto Ary A Seymour Christopher W CW Shankar-Hari Manu M Singh Vanessa V Tolppa Timo T Turgeon Alexis F AF Turner Anne M AM van de Veerdonk Frank L FL Green Cameron C Lewis Roger J RJ Angus Derek C DC McArthur Colin J CJ Berry Scott S Derde Lennie P G LPG Webb Steve A SA Gordon Anthony C AC

JAMA 20220401 13

<h4>Importance</h4>The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain.<h4>Objective</h4>To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19.<h4>Design, setting, and participants</h4>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 ...[more]

PMID: 35315874

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Dataset Information

Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

Similar Datasets

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