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

REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, 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 PG 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, 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, Vladimír Džavík, 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, M Margaret Knudson, Aaron E Kornblith, Matthew E Kutcher, Michael A Laffan, Francois Lamontagne, Grégoire 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, Andréa 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 EG Schutgens, Christopher W Seymour, Deborah M Siegal, Delcio G Silva, Aneesh B Singhal, Arthur S Slutsky, Dayna Solvason, Simon J Stanworth, 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, Scott M Berry, Colin J McArthur, Matthew D Neal, Judith S Hochman, Steven A Webb, Ryan Zarychanski

OAI: oai:www.repository.cam.ac.uk:1810/328936 • DOI: 10.17863/CAM.76383

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 therapeutic-dose 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. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).

Aged Anticoagulants covid-19 Critical Illness Female Hemorrhage Heparin Hospital Mortality Humans Logistic Models Male Middle Aged Odds Ratio Respiration Artificial Thrombosis Treatment Failure COVID-19 Drug Treatment