학술논문
A Randomized Trial of Nafamostat for Covid-19.
Document Type
Academic Journal
Author
Morpeth SC; Department of Microbiology and Infectious Diseases, Middlemore Hospital, Te Whatu Ora Counties Makukau, Auckland, New Zealand.; Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.; Venkatesh B; Department of Intensive Care Medicine, The University of Queensland at Princess Alexandra Hospital, Woolloongabba, QLD, Australia.; Department of Intensive Care Medicine, The University of Queensland at The Wesley Hospital, Toowong, QLD, Australia.; The George Institute for Global Health, Newtown, NSW, Australia.; Totterdell JA; Faculty of Medicine and Health, The University of Sydney School of Public Health, Sydney.; McPhee GM; Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; Mahar RK; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.; Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, VIC, Australia.; Jones M; Department of Health and Clinical Analytics, The University of Sydney School of Public Health, Sydney.; Bandara M; Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; Barina LA; Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; Basnet BK; Department of Medicine, Bir Hospital, Kathmandu, Nepal.; Department of Infectious Diseases, Perth Children's Hospital, Perth, WA, Australia.; Bowen AC; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, WA, Australia.; Burke AJ; Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.; Department of Infectious Diseases, Prince Charles Hospital, Merthyr Tydfil, United Kingdom.; Cochrane B; Department of Respiratory and Sleep Medicine, Campbelltown Hospital, Campbelltown, NSW, Australia.; Western Sydney University School of Medicine, Campbelltown, NSW, Australia.; Denholm JT; Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, VIC, Australia.; Dhungana A; Department of Medicine, National Academy of Medical Sciences at Bir Hospital, Kathmandu, Nepal.; Dore GJ; Viral Hepatitis Clinical Research Program, Kirby Institute, University of New South Wales, Kensington, NSW, Australia.; Department of Infectious Diseases, St. Vincent's Hospital, Melbourne, VIC, Australia.; Dotel R; Department of Infectious Diseases, Blacktown Hospital, Blacktown, NSW, Australia.; Duffy E; Department of Infectious Diseases, Te Whatu Ora Health New Zealand at Auckland City Hospital, Auckland, New Zealand.; School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.; Dummer J; Department of Medicine, University of Otago, Dunedin, New Zealand.; Respiratory Services, Dunedin Hospital, Dunedin, New Zealand.; Foo H; Department of Microbiology and Infectious Diseases, NSW Health Pathology Liverpool, Liverpool, NSW, Australia.; Gilbey TL; Department of Medicine and Infectious Diseases, Wagga Wagga Base Hospital, Wagga Wagga, Australia.; Hammond NE; Critical Care Program, The George Institute for Global Health, New Town, NSW, Australia.; Critical Care Program, The University of New South Wales, Sydney.; Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St. Leonards, NSW, Australia.; Hudson BJ; Department of Microbiology and Infectious Diseases, NSW Health Pathology, St. Leonards, St. Leonards, NSW, Australia.; Jha V; The George Institute for Global Health, Newtown, NSW, Australia.; Jevaji PR; Department of Research, The George Institute for Global Health, Pune, Maharashta, India.; John O; Department of Research, The George Institute for Global Health, Vellore, India.; Prasanna School of Public Health, Manipal Academy of Higher Education, Karnataka, India.; Joshi R; Department of Research, The George Institute for Global Health, Pune, Maharashta, India.; Kang G; Wellcome Trust Research Laboratory, Chartered Accountants Australia and New Zealand, Sydney.; Kaur B; Critical Care Program, The George Institute for Global Health, New Town, NSW, Australia.; Kim S; Zoonotic Virus Laboratory, Institut Pasteur Korea, Bundang-gu, Gyeonggi-do, Republic of Korea.; Das SK; Department of Internal Medicine, Maharajgunj Medical Campus, Institute of Medicine, Maharajgunj, Nepal.; Lau JSY; Department of Infectious Diseases, Eastern Health, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; Littleford R; UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Queensland, QLD, Australia.; Marsh JA; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, WA, Australia.; Centre for Child Health Research, University of Western Australia Medical School, Nedlands, WA, Australia.; Marschner IC; NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney.; Matthews G; Department of Infectious Diseases, St. Vincent's Hospital Sydney, Sydney.; Therapeutic and Vaccine Research Program, The Kirby Institute at The University of New South Wales, Kensington, NSW, Australia.; Maze MJ; Department of Medicine, University of Otago Christchurch, Christchurch, New England.; McArthur CJ; Department of Critical Care Medicine, Te Whatu Ora - Health New Zealand, Wellington, New Zealand.; McFadyen JD; Department of Clinical Haematology, Alfred Hospital, Melbourne, VIC, Australia.; Atherothrombosis and Vascular Biology Program, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.; McMahon JH; Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia.; McQuilten ZK; Department of Haematology, Monash Health, Melbourne, VIC, Australia.; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.; Molton J; Department of Infectious Diseases, Western Health, Footscray, VIC, Australia.; Mora JM; Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; Mudaliar V; Department of Research, The George Institute for Global Health, Pune, Maharashta, India.; Nguyen V; Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; O'Sullivan MVN; Department of Microbiology and Infectious Diseases, NSW Health Pathology Westmead Hospital, Newcastle, NSW, Australia.; Faculty of Medicine and Health, University of Sydney Westmead Clinical School, Sydney.; Pant S; Department of Internal Medicine, Maharajgunj Medical Campus, Institute of Medicine, Maharajgunj, Nepal.; Park JE; Business Development Team, Chong Kun Dang Pharmaceutical Corp., Dongbaekjukjeon-daero, Giheung-gu Yongin, Kyeonggi-do, Republic of Korea.; Paterson DL; Saw Swee Hock School of Public Health, National Institute of Singapore, Singapore.; Price DJ; Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.; Raymond N; Department of Medicine, Te Whatu Ora Health New Zealand Capital, Coast and Hutt Valley, Wellington, New Zealand.; Department of Medicine, Wellington School of Medicine, University of Otago, Wellington, New Zealand.; Rees MA; Department of Respiratory and Sleep Medicine, The Royal Melbourne Hospital, Melbourne, VIC, Australia.; Robinson JO; Department of Infectious Diseases, Royal Perth Hospital, Perth, WA, Australia.; Department of Microbiology, PathWest Laboratory Medicine, Nedlands, WA, Australia.; Rogers BA; Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, VIC, Australia.; Department of Infectious Diseases, Monash Health, Clayton, VIC, Australia.; Ryu WS; Virology, Institute Pasteur Korea, Bundang-gu, Gyeonggi-do, Republic of Korea.; Sasadeusz J; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, VIC, Australia.; Shum O; Department of Infectious Diseases, Wollongong Hospital, Kingoonya, NSW, Australia.; Graduate School of Medicine, University of Wollongong, Wollonngong, NSW, Australia.; Snelling TL; Faculty of Medicine and Health, The University of Sydney School of Public Health, Sydney.; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, WA, Australia.; Sommerville C; Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; Trask N; Chartered Accountants Australia and New Zealand, Sydney.; Lewin SR; Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, VIC, Australia.; Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia.; Hills TE; Department of Clinical Research, Medical Research Institute of New Zealand, Wellington, New Zealand.; Department of Infectious Diseases, Auckland City Hospital, Auckland, New Zealand.; Davis JS; School of Medicine and Public Health, The University of Newcastle, New Castle, Australia.; Global and Tropical Health Division, Menzies School of Health Research, Darwin, NT, Australia.; Roberts JA; Faculty of Medicine, The University of Queensland Centre for Clinical Research, Herston, QLD, Australia.; Metro North Health, Herston Infectious Diseases Institute, Herston, QLD, Australia.; Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.; Division of Anaesthesiology, Critical Care Emergency and Pain Medicine, Nîmes University Hospital at The University of Montpellier, Nîmes, France.; Tong SYC; Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, VIC, 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: Nafamostat mesylate is a potent in vitro antiviral agent that inhibits the host transmembrane protease serine 2 enzyme used by severe acute respiratory syndrome coronavirus 2 for cell entry. METHODS: This open-label, pragmatic, randomized clinical trial in Australia, New Zealand, and Nepal included noncritically ill hospitalized patients with coronavirus disease 2019 (Covid-19). Participants were randomly assigned to usual care or usual care plus nafamostat. The primary end point was death (any cause) or receipt of new invasive or noninvasive ventilation or vasopressor support within 28 days after randomization. Analysis was with a Bayesian logistic model in which an adjusted odds ratio <1.0 indicates improved outcomes with nafamostat. Enrollment was closed due to falling numbers of eligible patients. RESULTS: We screened 647 patients in 21 hospitals (15 in Australia, 4 in New Zealand, and 2 in Nepal) and enrolled 160 participants from May 2021 to August 2022. In the intention-to-treat population, the primary end point occurred in 8 (11%) of 73 patients with usual care and 4 (5%) of 82 with nafamostat. The median adjusted odds ratio for the primary end point for nafamostat was 0.40 (95% credible interval, 0.12 to 1.34) with a posterior probability of effectiveness (adjusted odds ratio <1.0) of 93%. For usual care compared with nafamostat, hyperkalemia occurred in 1 (1%) of 67 and 7 (9%) of 78 participants, respectively, and clinically relevant bleeding occurred in 1 (1%) of 73 and 7 (8%) of 82 participants. CONCLUSIONS: Among hospitalized patients with Covid-19, there was a 93% posterior probability that nafamostat reduced the odds of death or organ support. Prespecified stopping criteria were not met, precluding definitive conclusions. Hyperkalemia and bleeding were more common with nafamostat. (Funded by ASCOT and others; ClinicalTrials.gov number, NCT04483960.)