Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Ewan C. Goligher; Charlotte A. Bradbury; Bryan J. McVerry; Patrick R. Lawler; Jeffrey S. Berger; Michelle N. Gong; Marc Carrier; Harmony R. Reynolds; Anand Kumar; Alexis F. Turgeon; Lucy Z. Kornblith; Susan R. Kahn; John C. Marshall; Keri S. Kim; Brett L. Houston; Lennie P. G. Derde; Mary Cushman; Tobias Tritschler; Derek C. Angus; Lucas C. Godoy; Zoe McQuilten; Bridget-Anne Kirwan; Michael E. Farkouh; Maria M. Brooks; Roger J. Lewis; Lindsay R. Berry; Elizabeth Lorenzi; Anthony C. Gordon; Scott M. Berry; Colin J. McArthur; Matthew D. Neal; Judith S. Hochman; Steven A. Webb; Ryan Zarychanski; Tania Ahuja; Farah Al-Beidh; Djillali Annane; Yaseen M. Arabi; Diptesh Aryal; Lisa Baumann Kreuziger; Abi Beane; Zahra Bhimani; Shailesh Bihari; Henny H. Billett; Lindsay Bond; Marc Bonten; Frank Brunkhorst; Meredith Buxton; Adrian Buzgau; Lana A. Castellucci; Sweta Chekuri; Jen-Ting Chen; Allen C. Cheng; Tamta Chkhikvadze; Benjamin Coiffard; Aira Contreras; Todd W. Costantini; Sophie de Brouwer; Michelle A. Detry; Abhijit Duggal; Vladimir Dzavik; Mark B. Effron; Heather F. Eng; Jorge Escobedo; Lise J. Estcourt; Brendan M. Everett; Dean A. Fergusson; Mark Fitzgerald; Robert A. Fowler; Joshua D. Froess; Zhuxuan Fu; Jean P. Galanaud; Benjamin T. Galen; Sheetal Gandotra; Timothy D. Girard; Andrew L. Goodman; Herman Goossens; Cameron Green; Yonatan Y. Greenstein; Peter L. Gross; Rashan Haniffa; Sheila M. Hegde; Carolyn M. Hendrickson; Alisa M. Higgins; Alexander A. Hindenburg; Aluko A. Hope; James M. Horowitz; Christopher M. Horvat; David T. Huang; Kristin Hudock; Beverley J. Hunt; Mansoor Husain; Robert C. Hyzy; Jeffrey R. Jacobson; Devachandran Jayakumar; Norma M. Keller; Akram Khan; Yuri Kim; Andrei Kindzelski; Andrew J. King; Aaron E. Kornblith; Matthew E. Kutcher; Michael A. Laffan; Francois Lamontagne; Gregoire Le Gal; Christine M. Leeper; Eric S. Leifer; George Lim; Felipe Gallego Lima; Kelsey Linstrum; Edward Litton; Jose Lopez-Sendon; Sylvain A. Lother; Nicole Marten; Andrea Saud Marinez; Mary Martinez; Eduardo Mateos Garcia; Stavroula Mavromichalis; Daniel F. McAuley; Emily G. McDonald; Anna McGlothlin; Shay P. McGuinness; Saskia Middeldorp; Stephanie K. Montgomery; Paul R. Mouncey; Srinivas Murthy; Girish B. Nair; Rahul Nair; Alistair D. Nichol; Jose C. Nicolau; Brenda Nunez-Garcia; John J. Park; Pauline K. Park; Rachael L. Parke; Jane C. Parker; Sam Parnia; Jonathan D. Paul; Mauricio Pompilio; John G. Quigley; Robert S. Rosenson; Natalia S. Rost; Kathryn Rowan; Fernanda O. Santos; Marlene Santos; Mayler O. Santos; Lewis Satterwhite; Christina T. Saunders; Jake Schreiber; Roger E. G. Schutgens; Christopher W. Seymour; Deborah M. Siegal; Delcio G. Silva; Aneesh B. Singhal; Arthur S. Slutsky; Dayna Solvason; Anne M. Turner; Wilma Van Bentum-Puijk; Frank L. van de Veerdonk; Sean van Diepen; Gloria Vazquez-Grande; Lana Wahid; Vanessa Wareham; R. Jay Widmer; Jennifer G. Wilson; Eugene Yuriditsky; Yongqi Zhong; ACTIV-4a Investigators

doi:10.1056/NEJMoa2103417

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Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Journal article

Peer reviewed

Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Ewan C. Goligher, Charlotte A. Bradbury, Bryan J. McVerry, Patrick R. Lawler, Jeffrey S. Berger, Michelle N. Gong, Marc Carrier, Harmony R. Reynolds, Anand Kumar, Alexis F. Turgeon, …

The New England journal of medicine, Vol.385(9), pp.777-789

26/08/2021

DOI: https://doi.org/10.1056/NEJMoa2103417

PMID: 34351722

Abstract

General & Internal Medicine

Life Sciences & Biomedicine

Medicine, General & Internal

Science & Technology

BACKGROUND Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeuticdose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis.

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Title: Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
Creators - without role: Ewan C. Goligher - University of Toronto
Charlotte A. Bradbury - University of Bristol
Bryan J. McVerry - University of Pittsburgh
Patrick R. Lawler - University of Toronto
Jeffrey S. Berger - Supreme Council Of Health
Michelle N. Gong - The Bronx Defenders
Marc Carrier - Ottawa Hosp Res Inst, Ottawa, ON 105, Canada
Harmony R. Reynolds - Supreme Council Of Health
Anand Kumar - University of Manitoba
Alexis F. Turgeon - Univ Laval, Quebec City, PQ, Canada
Lucy Z. Kornblith - Univ Calif San Francisco, Zuckerberg San Francisco Gen Hosp, San Francisco, CA 94143 USA
Susan R. Kahn - McGill University
John C. Marshall - St Michaels Hosp Unity Hlth, Toronto, ON, Canada
Keri S. Kim - University of Illinois Urbana-Champaign
Brett L. Houston - University of Manitoba
Lennie P. G. Derde - Utrecht University
Mary Cushman - University of Vermont
Tobias Tritschler - University of Bern
Derek C. Angus - University of Pittsburgh
Lucas C. Godoy - University of Toronto
Zoe McQuilten - Monash University
Bridget-Anne Kirwan - Supreme Council Of Health
Michael E. Farkouh - University of Toronto
Maria M. Brooks - University of Pittsburgh
Roger J. Lewis - College Station Medical Center
Lindsay R. Berry - Berry
Elizabeth Lorenzi - Berry
Anthony C. Gordon - Imperial Coll London, London, England
Scott M. Berry - Berry
Colin J. McArthur - Monash University
Matthew D. Neal - University of Pittsburgh
Judith S. Hochman - Supreme Council Of Health
Steven A. Webb - Monash University
Ryan Zarychanski - University of Manitoba
Tania Ahuja - NYU Langone Hlth, NYU Langone Hosp, New York, NY USA
Farah Al-Beidh - Imperial Coll London, London, England
Djillali Annane - Univ Versailles St QuentinEn Yvelines, Federat Hosp Univ Saclay, Garches, France
Yaseen M. Arabi - King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia
Diptesh Aryal - Nepal Mediciti Hosp, Lalitpur, Nepal
Lisa Baumann Kreuziger - Versiti Blood Res Inst, Milwaukee, WI USA
Abi Beane - University of Oxford
Zahra Bhimani - St Michaels Hosp Unity Hlth, Toronto, ON, Canada
Shailesh Bihari - Flinders University
Henny H. Billett - The Bronx Defenders
Lindsay Bond - Ozmosis Research
Marc Bonten - Utrecht University
Frank Brunkhorst - Jena Univ Hosp, Jena, Germany
Meredith Buxton - Global Coalit Adapt Res, Los Angeles, CA USA
Adrian Buzgau - Monash University
Lana A. Castellucci - Ottawa Hosp Res Inst, Ottawa, ON 105, Canada
Sweta Chekuri - The Bronx Defenders
Jen-Ting Chen - The Bronx Defenders
Allen C. Cheng - Monash University
Tamta Chkhikvadze - Supreme Council Of Health
Benjamin Coiffard - Aix-Marseille University
Aira Contreras - Supreme Council Of Health
Todd W. Costantini - Supreme Council Of Health
Sophie de Brouwer - SOCAR Res, Nyon, Switzerland
Michelle A. Detry - Berry
Abhijit Duggal - Cleveland Clin, Cleveland, OH 44106 USA
Vladimir Dzavik - University of Toronto
Mark B. Effron - University of Queensland
Heather F. Eng - University of Pittsburgh
Jorge Escobedo - Inst Mexicano Seguro Social, Mexico City, DF, Mexico
Lise J. Estcourt - University of Oxford
Brendan M. Everett - Brigham and Women's Hospital
Dean A. Fergusson - Ottawa Hosp Res Inst, Ottawa, ON 105, Canada
Mark Fitzgerald - Berry
Robert A. Fowler - University of Toronto
Joshua D. Froess - University of Pittsburgh
Zhuxuan Fu - University of Pittsburgh
Jean P. Galanaud - University of Toronto
Benjamin T. Galen - Albert Einstein College of Medicine
Sheetal Gandotra - University of Alabama
Timothy D. Girard - University of Pittsburgh
Andrew L. Goodman - College Station Medical Center
Herman Goossens - University of Antwerp
Cameron Green - Monash University
Yonatan Y. Greenstein - Supreme Council Of Health
Peter L. Gross - McMaster University
Rashan Haniffa - Univ Coll London Hosp, London, England
Sheila M. Hegde - Brigham and Women's Hospital
Carolyn M. Hendrickson - Univ Calif San Francisco, Zuckerberg San Francisco Gen Hosp, San Francisco, CA 94143 USA
Alisa M. Higgins - Monash University
Alexander A. Hindenburg - NYU Langone Long Isl, Mineola, NY USA
Aluko A. Hope - The Bronx Defenders
James M. Horowitz - NYU Langone Hlth, NYU Langone Hosp, New York, NY USA
Christopher M. Horvat - University of Pittsburgh
David T. Huang - University of Pittsburgh
Kristin Hudock - University of Cincinnati
Beverley J. Hunt - Kings Healthcare Partners, London, England
Mansoor Husain - University of Toronto
Robert C. Hyzy - University of Michigan–Ann Arbor
Jeffrey R. Jacobson - University of Illinois Urbana-Champaign
Devachandran Jayakumar - Apollo Special Hosp OMR, Chennai, Tamil Nadu, India
Norma M. Keller - Supreme Council Of Health
Akram Khan - University of Portland
Yuri Kim - Brigham and Women's Hospital
Andrei Kindzelski - NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA
Andrew J. King - University of Pittsburgh
Aaron E. Kornblith - Univ Calif San Francisco, Zuckerberg San Francisco Gen Hosp, San Francisco, CA 94143 USA
Matthew E. Kutcher - University of Mississippi
Michael A. Laffan - Imperial Coll London, London, England
Francois Lamontagne - Univ Sherbrooke, Sherbrooke, PQ, Canada
Gregoire Le Gal - Ottawa Hosp Res Inst, Ottawa, ON 105, Canada
Christine M. Leeper - University of Pittsburgh
Eric S. Leifer - NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA
George Lim - Univ Calif Los Angeles, Los Angeles, CA USA
Felipe Gallego Lima - MED Institute
Kelsey Linstrum - University of Pittsburgh
Edward Litton - St Johns God Subiaco Hosp, Subiaco, WA, Australia
Jose Lopez-Sendon - Univ Autonoma, IdiPaz Res Inst, Madrid, Spain
Sylvain A. Lother - University of Manitoba
Nicole Marten - St Boniface Gen Hosp, Winnipeg, MB, Canada
Andrea Saud Marinez - Avanti
Mary Martinez - University of Pittsburgh
Eduardo Mateos Garcia - Inst Mexicano Seguro Social, Mexico City, DF, Mexico
Stavroula Mavromichalis - NHS Blood & Transplant, Oxford, England
Daniel F. McAuley - Queens University
Emily G. McDonald - McGill University
Anna McGlothlin - Berry
Shay P. McGuinness - Monash University
Saskia Middeldorp - Radboud University Nijmegen
Stephanie K. Montgomery - University of Pittsburgh
Paul R. Mouncey - Intens
Srinivas Murthy - University of British Columbia
Girish B. Nair - Beaumont Hlth, Royal Oak, MI USA
Rahul Nair - The Bronx Defenders
Alistair D. Nichol - Monash University
Jose C. Nicolau - MED Institute
Brenda Nunez-Garcia - Univ Calif San Francisco, Zuckerberg San Francisco Gen Hosp, San Francisco, CA 94143 USA
John J. Park - Univ Calif San Francisco, Zuckerberg San Francisco Gen Hosp, San Francisco, CA 94143 USA
Pauline K. Park - University of Michigan–Ann Arbor
Rachael L. Parke - Auckland City Hosp, Auckland, New Zealand
Jane C. Parker - Monash University
Sam Parnia - Supreme Council Of Health
Jonathan D. Paul - University of Chicago
Mauricio Pompilio - Hosp Coracao Mato Grosso, Campo Grande, MS, Brazil
John G. Quigley - University of Illinois Urbana-Champaign
Robert S. Rosenson - Supreme Council Of Health
Natalia S. Rost - Massachusetts Gen Hosp, Boston, MA 02114 USA
Kathryn Rowan - Intens
Fernanda O. Santos - Hosp 9 Julho, Sao Paulo, Brazil
Marlene Santos - St Michaels Hosp Unity Hlth, Toronto, ON, Canada
Mayler O. Santos - Clin Res Ctr, Inst Goiano Oncol & Hematol, Goiania, Go, Brazil
Lewis Satterwhite - University of Kansas
Christina T. Saunders - Berry
Jake Schreiber - Chartis Grp, Chicago, IL USA
Roger E. G. Schutgens - Utrecht University
Christopher W. Seymour - University of Pittsburgh
Deborah M. Siegal - University of Ottawa
Delcio G. Silva - Hosp Univ Maria Aparecida Pedrossia, Campo Grande, MS, Brazil
Aneesh B. Singhal - Massachusetts Gen Hosp, Boston, MA 02114 USA
Arthur S. Slutsky - University of Toronto
Dayna Solvason - University of Manitoba
Anne M. Turner - College Station Medical Center
Wilma Van Bentum-Puijk - Utrecht University
Frank L. van de Veerdonk - Radboud University Nijmegen
Sean van Diepen - University of Alberta
Gloria Vazquez-Grande - University of Manitoba
Lana Wahid - Duke University
Vanessa Wareham - Ozmosis Research
R. Jay Widmer - Baylor Medical Center at Garland
Jennifer G. Wilson - Stanford University
Eugene Yuriditsky - NYU Langone Hlth, NYU Langone Hosp, New York, NY USA
Yongqi Zhong - University of Pittsburgh
ACTIV-4a Investigators
Publication Details: The New England journal of medicine, Vol.385(9), pp.777-789
Publisher: Massachusetts Medical Soc
Number of pages: 13
Grant note: U.K. National Institute for Health Research (NIHR); National Institute for Health Research (NIHR) Canada Research Chair-Tier 2; Canada Research Chairs Minderoo Foundation RP-2015-06-18 / NIHR Research Professorship 215522 / Wellcome Trust 1OT2HL156812-01 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA NIHR Imperial Biomedical Research Centre APP1101719; APP1116530 / Australian National Health and Medical Research Council; National Health and Medical Research Council (NHMRC) of Australia CTN 2014-012 / Health Research Board of Ireland; Health Research Board - Ireland OTA-20-011 / National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 602525 / European Union through FP7-HEALTH-2013-INNOVATION: the Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) consortium AR7162822 / Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) PHRC-20-0147 / French Ministry of Health 158584 / Canadian Institutes of Health Research (Strategy for Patient-Oriented Research Innovative Clinical Trials Program); Canadian Institutes of Health Research (CIHR) 447335 / COVID-19 Rapid Research Operating Grant CancerCare Manitoba Foundation, Victoria General Hospital Foundation 101003589 / Horizon 2020 research and innovation program: the Rapid European Covid-19 Emergency Research response (RECOVER) consortium Translational Breast Cancer Research Consortium Ontario Ministry of Health; Ministry of Health and Long-Term Care, Ontario Lyonel G. Israels Research Chair in Hematology (University of Manitoba) Amgen Global Coalition for Adaptive Research Peter Munk Cardiac Centre; University of Toronto 16/631 / Health Research Council of New Zealand
Identifiers: 9921347108331
Academic Unit: King Abdulaziz University; King Saud Bin Abdulaziz University for Health Sciences
Language: English
Resource Type: Journal article