1. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
- Author
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REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Goligher, Ewan C, Bradbury, Charlotte A, McVerry, Bryan J, Lawler, Patrick R, Berger, Jeffrey S, Gong, Michelle N, Carrier, Marc, Reynolds, Harmony R, Kumar, Anand, Turgeon, Alexis F, Kornblith, Lucy Z, Kahn, Susan R, Marshall, John C, Kim, Keri S, Houston, Brett L, Derde, Lennie PG, Cushman, Mary, Tritschler, Tobias, Angus, Derek C, Godoy, Lucas C, McQuilten, Zoe, Kirwan, Bridget-Anne, Farkouh, Michael E, Brooks, Maria M, Lewis, Roger J, Berry, Lindsay R, Lorenzi, Elizabeth, Gordon, Anthony C, Ahuja, Tania, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Contreras, Aira, Costantini, Todd W, de Brouwer, Sophie, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Eng, Heather F, Escobedo, Jorge, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Froess, Joshua D, Fu, Zhuxuan, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, Girard, Timothy D, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Haniffa, Rashan, Hegde, Sheila M, Hendrickson, Carolyn M, Higgins, Alisa M, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Huang, David T, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei, King, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, Kutcher, Matthew E, Laffan, Michael A, Lamontagne, Francois, Le Gal, Grégoire, Leeper, Christine M, Leifer, Eric S, Lim, George, Gallego Lima, Felipe, Linstrum, Kelsey, Litton, Edward, Lopez-Sendon, Jose, Lother, Sylvain A, Marten, Nicole, Saud Marinez, Andréa, Martinez, Mary, Mateos Garcia, Eduardo, Mavromichalis, Stavroula, McAuley, Daniel F, McDonald, Emily G, McGlothlin, Anna, McGuinness, Shay P, Middeldorp, Saskia, Montgomery, Stephanie K, Mouncey, Paul R, Murthy, Srinivas, Nair, Girish B, Nair, Rahul, Nichol, Alistair D, Nicolau, Jose C, Nunez-Garcia, Brenda, Park, John J, Park, Pauline K, Parke, Rachael L, Parker, Jane C, Parnia, Sam, Paul, Jonathan D, Pompilio, Mauricio, Quigley, John G, Rosenson, Robert S, Rost, Natalia S, Rowan, Kathryn, Santos, Fernanda O, Santos, Marlene, Santos, Mayler O, Satterwhite, Lewis, Saunders, Christina T, Schreiber, Jake, Schutgens, Roger EG, Seymour, Christopher W, Siegal, Deborah M, Silva, Delcio G, Singhal, Aneesh B, Slutsky, Arthur S, Solvason, Dayna, Stanworth, Simon J, Turner, Anne M, van Bentum-Puijk, Wilma, van de Veerdonk, Frank L, van Diepen, Sean, Vazquez-Grande, Gloria, Wahid, Lana, Wareham, Vanessa, Widmer, R Jay, Wilson, Jennifer G, Yuriditsky, Eugene, Zhong, Yongqi, Berry, Scott M, McArthur, Colin J, Neal, Matthew D, Hochman, Judith S, Webb, Steven A, Zarychanski, Ryan, Bradbury, Charlotte A [0000-0001-5248-8165], McVerry, Bryan J [0000-0002-1175-4874], Lawler, Patrick R [0000-0001-5155-5071], Carrier, Marc [0000-0001-8296-2972], Kim, Keri S [0000-0002-8480-4801], Houston, Brett L [0000-0002-8776-4083], Cushman, Mary [0000-0002-7871-6143], Tritschler, Tobias [0000-0002-8775-0511], Godoy, Lucas C [0000-0001-6171-1269], Gordon, Anthony C [0000-0002-0419-547X], Ahuja, Tania [0000-0003-1833-4124], Aryal, Diptesh [0000-0002-1431-8293], Baumann Kreuziger, Lisa [0000-0002-1171-0548], Beane, Abi [0000-0001-7046-1580], Coiffard, Benjamin [0000-0002-8896-5346], Detry, Michelle A [0000-0002-2794-1439], Escobedo, Jorge [0000-0003-1942-7402], Estcourt, Lise J [0000-0003-4309-9162], Everett, Brendan M [0000-0002-6331-5224], Fu, Zhuxuan [0000-0002-9190-195X], Galen, Benjamin T [0000-0001-8172-258X], Girard, Timothy D [0000-0002-9833-4871], Greenstein, Yonatan Y [0000-0002-5718-4408], Haniffa, Rashan [0000-0002-8288-449X], Hegde, Sheila M [0000-0001-8157-8899], Hendrickson, Carolyn M [0000-0003-4662-2385], Higgins, Alisa M [0000-0001-8295-7559], Hindenburg, Alexander A [0000-0002-1232-2168], Horvat, Christopher M [0000-0002-1593-2252], Huang, David T [0000-0001-7649-1633], Jacobson, Jeffrey R [0000-0001-8929-994X], Kim, Yuri [0000-0001-5978-5779], King, Andrew J [0000-0002-9809-0563], Kutcher, Matthew E [0000-0003-4566-5359], Leifer, Eric S [0000-0001-6888-8307], Litton, Edward [0000-0002-5125-6829], Mateos Garcia, Eduardo [0000-0002-0904-4056], Mouncey, Paul R [0000-0002-8510-8517], Nunez-Garcia, Brenda [0000-0002-0355-4557], Parnia, Sam [0000-0002-6158-4404], Quigley, John G [0000-0003-3116-4545], Saunders, Christina T [0000-0003-4325-9568], Yuriditsky, Eugene [0000-0003-2263-9297], Zhong, Yongqi [0000-0002-4042-7450], Neal, Matthew D [0000-0001-8931-6236], and Apollo - University of Cambridge Repository
- Subjects
Male ,Heparin ,Critical Illness ,Anticoagulants ,COVID-19 ,Hemorrhage ,Thrombosis ,Middle Aged ,Respiration, Artificial ,COVID-19 Drug Treatment ,Logistic Models ,Odds Ratio ,Humans ,Female ,Hospital Mortality ,Treatment Failure ,Aged - Abstract
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
- Published
- 2021