학술논문

Anticoagulation Strategies in Non-Critically Ill Patients with Covid-19.
Document Type
Academic Journal
Author
McQuilten ZK; Monash University, Melbourne, Australia.; Monash Health, Melbourne, Australia.; Venkatesh B; University of Queensland, Brisbane, Australia.; The George Institute for Global Health, Sydney, Australia.; The George Institute for Global Health, Delhi, Delhi, India.; The Wesley Hospital, Brisbane, Queensland, Australia.; University of New South Wales, Sydney, New South Wales, Australia.; Jha V; The George Institute for Global Health, Delhi, Delhi, India.; Imperial College, London, England, United Kingdom.; Roberts J; University of Queensland, Brisbane, Australia.; Metro North Health, Brisbane, Queensland, Australia.; Morpeth SC; Middlemore Hospital, Auckland, North Island, New Zealand.; Totterdell JA; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; McPhee GM; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Abraham J; Christian Medical College, Ludhiana, Punjab, India.; Bam N; Institute of Medicine, Maharajgunj Medical Campus, Kathmandu, Bagmati, Nepal.; Bandara M; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Bangi AK; Jivanrekha Multispeciality Hospital, Pune, Maharashtra, India.; Barina LA; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Basnet BK; National Academy of Medical Sciences, Bir Hospital, Kathmandu, Bagmati, Nepal.; Bhally H; North Shore Hospital, Auckland, North Island, New Zealand.; Bhusal KR; Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Bagmati, Nepal.; Bogati U; National Academy of Medical Sciences, Bir Hospital, Kathmandu, Bagmati, Nepal.; Bowen AC; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.; Perth Children's Hospital, Perth, Western Australia, Australia.; Burke AJ; University of Queensland, Brisbane, Australia.; The Prince Charles Hospital, Brisbane, Queensland, Australia.; Christopher DJ; Christian Medical College, Vellore, Tamil Nadu, India.; Chunilal SD; Monash University, Melbourne, Australia.; Monash Medical Centre, Melbourne, Victoria, Australia.; Cochrane B; Campbelltown Hospital, Campbelltown, New South Wales, Australia.; Western Sydney University, Sydney, New South Wales, Australia.; Curnow JL; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Westmead Hospital, Sydney, New South Wales, Australia.; Das SK; Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Bagmati, Nepal.; Dhungana A; National Academy of Medical Sciences, Bir Hospital, Kathmandu, Bagmati, Nepal.; Di Tanna GL; The George Institute for Global Health, Sydney, Australia.; Dotel R; Blacktown Hospital, Sydney, New South Wales, Australia.; DSouza H; The George Institute for Global Health, Delhi, Delhi, India.; Dummer J; University of Otago, Dunedin, Otago, New Zealand.; Dunedin Hospital, Dunedin, Otago, New Zealand.; Dutta S; Postgraduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India.; Foo H; NSW Health Pathology, Sydney, New South Wales, Australia.; Gilbey TL; Wagga Wagga Base Hospital, Wagga Wagga, New South Wales, Australia.; Giles ML; Monash University, Melbourne, Australia.; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Goli K; Aditya Multi-speciality Hospital, Guntur, Andhra Pradesh, India.; Gordon A; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Royal Prince Alfred Hospital, Newborn Care, Melbourne, Victoria, Australia.; Gyanwali P; Institute of Medicine, Maharajgunj Medical Campus, Kathmandu, Bagmati, Nepal.; Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Bagmati, Nepal.; Haksar D; ITC Hotels, Gurugram, Haryana, India.; Hudson BJ; Royal North Shore Hospital, Sydney, New South Wales, Australia.; Jani MK; Apex Hospitals, Jaipur, Rajasthan, India.; Jevaji PR; The George Institute for Global Health, Delhi, Delhi, India.; Jhawar S; Apex Hospitals, Jaipur, Rajasthan, India.; Jindal A; Satguru Partap Singh Hospitals, Ludhiana, Punjab, India.; John MJ; Christian Medical College, Ludhiana, Punjab, India.; John M; Christian Medical College, Ludhiana, Punjab, India.; John FB; Christian Medical College, Vellore, Tamil Nadu, India.; John O; The George Institute for Global Health, Delhi, Delhi, India.; Manipal Academy of Higher Education, Udupi, Karnataka, India.; Jones M; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Joshi RD; The George Institute for Global Health, Delhi, Delhi, India.; Kamath P; The George Institute for Global Health, Delhi, Delhi, India.; Kang G; Christian Medical College, Vellore, Tamil Nadu, India.; Karki AR; National Academy of Medical Sciences, Bir Hospital, Kathmandu, Bagmati, Nepal.; Karmalkar AM; Sterling Multispeciality Hospital, Pune, Maharashtra, India.; Kaur B; The George Institute for Global Health, Sydney, Australia.; Koganti KC; Samishta Hospital & Research Institute, Guntur, Andhra Pradesh, India.; Koshy JM; Believers Church Medical College Hospital, Thiruvalla, Kerala, India.; Krishnamurthy MS; Believers Church Medical College Hospital, Thiruvalla, Kerala, India.; Lau JS; Eastern Health, Melbourne, Victoria, Australia.; The Alfred Hospital, Melbourne, Victoria, Australia.; Lewin SR; Monash Health, Melbourne, Australia.; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Lim LL; Monash University, Melbourne, Australia.; Marschner IC; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Marsh JA; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.; Maze MJ; University of Otago, Dunedin, Otago, New Zealand.; McGree JM; Queensland University of Technology, Brisbane, Queensland, Australia.; McMahon JH; The Alfred Hospital, Melbourne, Victoria, Australia.; Medcalf RL; Monash University, Melbourne, Australia.; Merriman EG; North Shore Hospital, Auckland, North Island, New Zealand.; Misal AP; Core Hospital, Chakan, Maharashtra, India.; Mora JM; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Mudaliar VK; The George Institute for Global Health, Delhi, Delhi, India.; Nguyen V; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; O'Sullivan MV; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Westmead Hospital, Sydney, New South Wales, Australia.; NSW Health Pathology, Sydney, New South Wales, Australia.; Pant S; Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Bagmati, Nepal.; Pant P; Institute of Medicine, Maharajgunj Medical Campus, Kathmandu, Bagmati, Nepal.; Paterson DL; National Institute of Singapore, Singapore, Singapore, Singapore.; Price DJ; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Melbourne School of Population & Global Health, University of Melbourne, Melbourne, Victoria, Australia.; Rees MA; Respiratory and Sleep Medicine, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.; Robinson JO; College of Science, Health, Engineering and Education, Discipline of Health, Murdoch University, Perth, Western Australia, Australia.; PathWest Laboratory Medicine, Perth, Western Australia, Australia.; Rogers BA; Monash University, Melbourne, Australia.; Monash Health, Melbourne, Australia.; Samuel S; Christian Medical College, Ludhiana, Punjab, India.; Sasadeusz J; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Sharma D; Maharaja Agrasen Superspeciality Hospital, Delhi, Delhi, India.; Sharma PK; Maharaja Agrasen Superspeciality Hospital, Delhi, Delhi, India.; Shrestha R; Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Bagmati, Nepal.; Shrestha SK; National Academy of Medical Sciences, Bir Hospital, Kathmandu, Bagmati, Nepal.; Shrestha P; National Academy of Medical Sciences, Bir Hospital, Kathmandu, Bagmati, Nepal.; Shukla U; Symbiosis University Hospital & Research Centre, Pune, Maharashtra, India.; Shum O; The Wollongong Hospital, Wollongong, New South Wales, Australia.; University of Wollongong, Wollongong, New South Wales, Australia.; Sommerville C; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Spelman T; Karolinska Institute, Solna, Stockholm, Sweden.; Burnet Institute, Melbourne, Victoria, Australia.; Sullivan RP; St. George Hospital, School of Clinical Medicine, UNSW Medicine & Health, Sydney, New South Wales, Australia.; Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.; Thatavarthi U; Samishta Hospital & Research Institute, Guntur, Andhra Pradesh, India.; Tran HA; Monash University, Melbourne, Australia.; The Alfred Hospital, Melbourne, Victoria, Australia.; Trask N; Chartered Accountants Australia and New Zealand, Perth, Western Australia, Australia.; Whitehead CL; The Royal Women's Hospital, The University of Melbourne, Melbourne, Victoria, Australia.; Mahar RK; Melbourne School of Population & Global Health, University of Melbourne, Melbourne, Victoria, Australia.; Murdoch Children's Research Institute, Perth, Western Australia, Australia.; Hammond NE; The George Institute for Global Health, Sydney, Australia.; Royal North Shore Hospital, Sydney, New South Wales, Australia.; McFadyen JD; The Alfred Hospital, Melbourne, Victoria, Australia.; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.; Snelling TL; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.; Davis JS; Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.; University of Newcastle, Newcastle, New South Wales, Australia.; Denholm JT; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Tong SYC; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Source
Publisher: NEJM Group, a division of the Massachusetts Medical Society Country of Publication: United States NLM ID: 9918317485806676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2766-5526 (Electronic) Linking ISSN: 27665526 NLM ISO Abbreviation: NEJM Evid Subsets: MEDLINE
Subject
Language
English
Abstract
BACKGROUND: Optimal thromboprophylaxis for hospitalized patients with coronavirus disease 2019 (Covid-19) is uncertain. METHODS: In an open-label, adaptive platform trial, we randomly assigned hospitalized adults with Covid-19 to low-dose low-molecular-weight heparin thromboprophylaxis or intermediate-dose or low-dose plus aspirin. In response to external evidence, the aspirin intervention was discontinued and a therapeutic-dose arm added. The primary end point was death or the requirement for new organ support by day 28, analyzed with a Bayesian logistic model. Enrolment was closed as a result of operational constraints. RESULTS: Between February 2021 and March 2022, 1574 patients were randomly assigned. Among 1526 participants included in the analysis (India, n=1273; Australia and New Zealand, n=138; and Nepal, n=115), the primary outcome occurred in 35 (5.9%) of 596 in low-dose, 25 (4.2%) of 601 in intermediate-dose, 20 (7.2%) of 279 in low-dose plus aspirin, and 7 (14%) of 50 in therapeutic-dose anticoagulation. Compared with low-dose thromboprophylaxis, the median adjusted odds ratio for the primary outcome for intermediate-dose was 0.74 (95% credible interval [CrI], 0.43 to 1.27; posterior probability of effectiveness [adjusted odds ratio<1; Pr], 86%), for low-dose plus aspirin 0.88 (95% CrI, 0.47 to 1.64; Pr, 65%), and for therapeutic-dose anticoagulation 2.22 (95% CrI, 0.77 to 6.20; Pr, 7%). Overall thrombotic and bleeding rates were 0.8% and 0.4%, respectively. There were 10 serious adverse reactions related to anticoagulation strategy, of which nine were grade 1 or 2 across study interventions and one grade 4 episode of retroperitoneal hematoma in a patient receiving intermediate-dose anticoagulation. CONCLUSIONS: In hospitalized non–critically ill adults with Covid-19, compared with low-dose, there was an 86% posterior probability that intermediate-dose, 65% posterior probability that low-dose plus aspirin, and a 7% posterior probability that therapeutic-dose anticoagulation reduced the odds of death or requirement for organ support. No treatment strategy met prespecified stopping criteria before trial closure, precluding definitive conclusions. (Funded by Australian National Health and Medical Research Council or Medical Research Future Fund Investigator and Practitioner Grants and others; ClinicalTrials.gov number, NCT04483960.)

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