Goligher, Ewan CEwan CGoligherBradbury, Charlotte ACharlotte ABradburyMcVerry, Bryan JBryan JMcVerryLawler, Patrick RPatrick RLawlerBerger, Jeffrey SJeffrey SBergerGong, Michelle NMichelle NGongCarrier, MarcMarcCarrierReynolds, Harmony RHarmony RReynoldsKumar, AnandAnandKumarTurgeon, Alexis FAlexis FTurgeonKornblith, Lucy ZLucy ZKornblithKahn, Susan RSusan RKahnMarshall, John CJohn CMarshallKim, Keri SKeri SKimHouston, Brett LBrett LHoustonDerde, Lennie P GLennie P GDerdeCushman, MaryMaryCushmanTritschler, TobiasTobiasTritschlerAngus, Derek CDerek CAngusGodoy, Lucas CLucas CGodoyMcQuilten, ZoeZoeMcQuiltenKirwan, Bridget-AnneBridget-AnneKirwanFarkouh, Michael EMichael EFarkouhBrooks, Maria MMaria MBrooksLewis, Roger JRoger JLewisBerry, Lindsay RLindsay RBerryLorenzi, ElizabethElizabethLorenziGordon, Anthony CAnthony CGordonAhuja, TaniaTaniaAhujaAl-Beidh, FarahFarahAl-BeidhAnnane, DjillaliDjillaliAnnaneArabi, Yaseen MYaseen MArabiAryal, DipteshDipteshAryalBaumann Kreuziger, LisaLisaBaumann KreuzigerBeane, AbiAbiBeaneBhimani, ZahraZahraBhimaniBihari, ShaileshShaileshBihariBillett, Henny HHenny HBillettBond, LindsayLindsayBondBonten, MarcMarcBontenBrunkhorst, FrankFrankBrunkhorstBuxton, MeredithMeredithBuxtonBuzgau, AdrianAdrianBuzgauCastellucci, Lana ALana ACastellucciChekuri, SwetaSwetaChekuriChen, Jen-TingJen-TingChenCheng, Allen CAllen CChengChkhikvadze, TamtaTamtaChkhikvadzeCoiffard, BenjaminBenjaminCoiffardContreras, AiraAiraContrerasCostantini, Todd WTodd WCostantinide Brouwer, SophieSophiede BrouwerDetry, Michelle AMichelle ADetryDuggal, AbhijitAbhijitDuggalDžavík, VladimírVladimírDžavíkEffron, Mark BMark BEffronEng, Heather FHeather FEngEscobedo, JorgeJorgeEscobedoEstcourt, Lise JLise JEstcourtEverett, Brendan MBrendan MEverettFergusson, Dean ADean AFergussonFitzgerald, MarkMarkFitzgeraldFowler, Robert ARobert AFowlerFroess, Joshua DJoshua DFroessFu, ZhuxuanZhuxuanFuGalanaud, Jean PJean PGalanaudGalen, Benjamin TBenjamin TGalenGandotra, SheetalSheetalGandotraGirard, Timothy DTimothy DGirardGoodman, Andrew LAndrew LGoodmanGoossens, HermanHermanGoossensGreen, CameronCameronGreenGreenstein, Yonatan YYonatan YGreensteinGross, Peter LPeter LGrossHaniffa, RashanRashanHaniffaHegde, Sheila MSheila MHegdeHendrickson, Carolyn MCarolyn MHendricksonHiggins, Alisa MAlisa MHigginsHindenburg, Alexander AAlexander AHindenburgHope, Aluko AAluko AHopeHorowitz, James MJames MHorowitzHorvat, Christopher MChristopher MHorvatHuang, David TDavid THuangHudock, KristinKristinHudockHunt, Beverley JBeverley JHuntHusain, MansoorMansoorHusainHyzy, Robert CRobert CHyzyJacobson, Jeffrey RJeffrey RJacobsonJayakumar, DevachandranDevachandranJayakumarKeller, Norma MNorma MKellerKhan, AkramAkramKhanKim, YuriYuriKimKindzelski, AndreiAndreiKindzelskiKing, Andrew JAndrew JKingKnudson, M MargaretM MargaretKnudsonKornblith, Aaron EAaron EKornblithKutcher, Matthew EMatthew EKutcherLaffan, Michael AMichael ALaffanLamontagne, FrancoisFrancoisLamontagneLe Gal, GrégoireGrégoireLe GalLeeper, Christine MChristine MLeeperLeifer, Eric SEric SLeiferLim, GeorgeGeorgeLimGallego Lima, FelipeFelipeGallego LimaLinstrum, KelseyKelseyLinstrumLitton, EdwardEdwardLittonLopez-Sendon, JoseJoseLopez-SendonLother, Sylvain ASylvain ALotherMarten, NicoleNicoleMartenSaud Marinez, AndréaAndréaSaud MarinezMartinez, MaryMaryMartinezMateos Garcia, EduardoEduardoMateos GarciaMavromichalis, StavroulaStavroulaMavromichalisMcAuley, Daniel FDaniel FMcAuleyMcDonald, Emily GEmily GMcDonaldMcGlothlin, AnnaAnnaMcGlothlinMcGuinness, Shay PShay PMcGuinnessMiddeldorp, SaskiaSaskiaMiddeldorpMontgomery, Stephanie KStephanie KMontgomeryMouncey, Paul RPaul RMounceyMurthy, SrinivasSrinivasMurthyNair, Girish BGirish BNairNair, RahulRahulNairNichol, Alistair DAlistair DNicholNicolau, Jose CJose CNicolauNunez-Garcia, BrendaBrendaNunez-GarciaPark, John JJohn JParkPark, Pauline KPauline KParkParke, Rachael LRachael LParkeParker, Jane CJane CParkerParnia, SamSamParniaPaul, Jonathan DJonathan DPaulPompilio, MauricioMauricioPompilioQuigley, John GJohn GQuigleyRosenson, Robert SRobert SRosensonRost, Natalia SNatalia SRostRowan, KathrynKathrynRowanSantos, Fernanda OFernanda OSantosSantos, MarleneMarleneSantosSantos, Mayler OMayler OSantosSatterwhite, LewisLewisSatterwhiteSaunders, Christina TChristina TSaundersSchreiber, JakeJakeSchreiberSchutgens, Roger E GRoger E GSchutgensSeymour, Christopher WChristopher WSeymourSiegal, Deborah MDeborah MSiegalSilva, Delcio GDelcio GSilvaSinghal, Aneesh BAneesh BSinghalSlutsky, Arthur SArthur SSlutskySolvason, DaynaDaynaSolvasonStanworth, Simon JSimon JStanworthTurner, Anne MAnne MTurnervan Bentum-Puijk, WilmaWilmavan Bentum-Puijkvan de Veerdonk, Frank LFrank Lvan de Veerdonkvan Diepen, SeanSeanvan DiepenVazquez-Grande, GloriaGloriaVazquez-GrandeWahid, LanaLanaWahidWareham, VanessaVanessaWarehamWidmer, R JayR JayWidmerWilson, Jennifer GJennifer GWilsonYuriditsky, EugeneEugeneYuriditskyZhong, YongqiYongqiZhongBerry, Scott MScott MBerryMcArthur, Colin JColin JMcArthurNeal, Matthew DMatthew DNealHochman, Judith SJudith SHochmanWebb, Steven ASteven AWebbZarychanski, RyanRyanZarychanski2024-09-022024-09-022021-08-26https://boris-portal.unibe.ch/handle/20.500.12422/43798BACKGROUND 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.).enarticle10.48350/1594793435172210.1056/NEJMoa2103417