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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; Lawler, Patrick R; Stanworth, Simon J; McVerry, Bryan J; McQuilten, Zoe; Higgins, Alisa M; Mouncey, Paul R; Al-Beidh, Farah; Rowan, Kathryn M; Berry, Lindsay R; Lorenzi, Elizabeth; Zarychanski, Ryan; Arabi, Yaseen M; Annane, Djillali; Beane, Abi; van Bentum-Puijk, Wilma; Bhimani, Zahra; Bihari, Shailesh; Bonten, Marc J M; Brunkhorst, Frank M; Buzgau, Adrian; Buxton, Meredith; Carrier, Marc; Cheng, Allen C; Cove, Matthew; Detry, Michelle A; Estcourt, Lise J; Fitzgerald, Mark; Girard, Timothy D; Goligher, Ewan C; Goossens, Herman; Haniffa, Rashan; Hills, Thomas; Huang, David T; Horvat, Christopher M; Hunt, Beverley J; Ichihara, Nao; Lamontagne, Francois; Leavis, Helen L; Linstrum, Kelsey M; Litton, Edward; Marshall, John C; McAuley, Daniel F; McGlothlin, Anna; McGuinness, Shay P; Middeldorp, Saskia; Montgomery, Stephanie K; Morpeth, Susan C; Murthy, Srinivas; Neal, Matthew D.
  • Bradbury CA; University of Bristol, Bristol, England.
  • Lawler PR; Peter Munk Cardiac Centre at University Health Network, Toronto, Ontario, Canada.
  • Stanworth SJ; University of Toronto, Toronto, Ontario, Canada.
  • McVerry BJ; University of Oxford, Oxford, England.
  • McQuilten Z; NHS Blood and Transplant, Oxford, England.
  • Higgins AM; University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Mouncey PR; Monash University, Melbourne, Victoria, Australia.
  • Al-Beidh F; Monash Health, Melbourne, Victoria, Australia.
  • Rowan KM; Monash University, Melbourne, Victoria, Australia.
  • Berry LR; Intensive Care National Audit and Research Centre (ICNARC), London, England.
  • Lorenzi E; Imperial College London, London, England.
  • Zarychanski R; Intensive Care National Audit and Research Centre (ICNARC), London, England.
  • Arabi YM; Berry Consultants, Austin, Texas.
  • Annane D; Berry Consultants, Austin, Texas.
  • Beane A; University of Manitoba, Winnipeg, Canada.
  • van Bentum-Puijk W; King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
  • Bhimani Z; Hospital Raymond Poincaré (Assistance Publique Hôpitaux de Paris), Garches, France.
  • Bihari S; Université Versailles SQY-Université Paris Saclay, Montigny-le-Bretonneux, France.
  • Bonten MJM; University of Oxford, Oxford, England.
  • Brunkhorst FM; University Medical Center Utrecht, Utrecht, the Netherlands.
  • Buzgau A; St Michael's Hospital Unity Health, Toronto, Ontario, Canada.
  • Buxton M; Flinders University, Bedford Park, South Australia, Australia.
  • Carrier M; University Medical Center Utrecht, Utrecht, the Netherlands.
  • Cheng AC; Jena University Hospital, Jena, Germany.
  • Cove M; Monash University, Melbourne, Victoria, Australia.
  • Detry MA; Global Coalition for Adaptive Research, Los Angeles, California.
  • Estcourt LJ; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
  • Fitzgerald M; Institut du Savoir Montfort, Ottawa, Ontario, Canada.
  • Girard TD; Monash University, Melbourne, Victoria, Australia.
  • Goligher EC; Alfred Health, Melbourne, Victoria, Australia.
  • Goossens H; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Haniffa R; Berry Consultants, Austin, Texas.
  • Hills T; NHS Blood and Transplant, Oxford, England.
  • Huang DT; Berry Consultants, Austin, Texas.
  • Horvat CM; University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Hunt BJ; Peter Munk Cardiac Centre at University Health Network, Toronto, Ontario, Canada.
  • Ichihara N; University of Toronto, Toronto, Ontario, Canada.
  • Lamontagne F; University of Antwerp, Wilrijk, Belgium.
  • Leavis HL; University of Oxford, Bangkok, Thailand.
  • Linstrum KM; National Intensive Care Surveillance (NICST), Colombo, Sri Lanka.
  • Litton E; Medical Research Institute of New Zealand (MRINZ), Wellington, New Zealand.
  • Marshall JC; University of Pittsburgh, Pittsburgh, Pennsylvania.
  • McAuley DF; UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
  • McGlothlin A; Kings Healthcare Partners, London, England.
  • McGuinness SP; The University of Tokyo, Tokyo, Japan.
  • Middeldorp S; Université de Sherbrooke, Sherbrooke, Québec, Canada.
  • Montgomery SK; University Medical Center Utrecht, Utrecht, the Netherlands.
  • Morpeth SC; University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Murthy S; Fiona Stanley Hospital, Perth, Western Australia, Australia.
  • Neal MD; University of Western Australia, Perth, Australia.
JAMA ; 327(13): 1247-1259, 2022 04 05.
Article in English | MEDLINE | ID: covidwho-1801957
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Platelet Aggregation Inhibitors / Critical Illness / Venous Thromboembolism / COVID-19 Type of study: Controlled clinical trial / Etiology study / Observational study / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: JAMA Year: 2022 Document Type: Article Affiliation country: Jama.2022.2910

Full text: Available Collection: International databases Database: MEDLINE Main subject: Platelet Aggregation Inhibitors / Critical Illness / Venous Thromboembolism / COVID-19 Type of study: Controlled clinical trial / Etiology study / Observational study / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: JAMA Year: 2022 Document Type: Article Affiliation country: Jama.2022.2910