A Randomized Trial of Nafamostat for Covid-19

Susan C Morpeth; Balasubramanian Venkatesh; James A Totterdell; Grace M McPhee; Robert K Mahar; Mark Jones; Methma Bandara; Lauren A Barina; Bhupendra K Basnet; Asha C Bowen; Andrew J Burke; Belinda Cochrane; Justin T Denholm; Ashesh Dhungana; Gregory J Dore; Ravindra Dotel; Eamon Duffy; Jack Dummer; Hong Foo; Timothy L Gilbey; Naomi E Hammond; Bernard J Hudson; Vivekanand Jha; Purnima R Jevaji; Oommen John; Rajesh Joshi; Gagandeep Kang; Baldeep Kaur; Seungtaek Kim; Santa Kumar Das; Jillian S Y Lau; Roberta Littleford; Julie A Marsh; Ian C Marschner; Gail Matthews; Michael J Maze; Colin J McArthur; James D McFadyen; James H McMahon; Zoe K McQuilten; James Molton; Jocelyn M Mora; Vijaybabu Mudaliar; Vi Nguyen; Matthew V N O'Sullivan; Suman Pant; Jaha E Park; David L Paterson; David J Price; Nigel Raymond; Megan A Rees; James O Robinson; Benjamin A Rogers; Wang-Shick Ryu; Joe Sasadeusz; Omar Shum; Thomas L Snelling; Christine Sommerville; Nanette Trask; Sharon R Lewin; Thomas E Hills; Joshua S Davis; Jason A Roberts; Steven Y C Tong

doi:10.1056/EVIDoa2300132

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A Randomized Trial of Nafamostat for Covid-19

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A Randomized Trial of Nafamostat for Covid-19

Susan C Morpeth, Balasubramanian Venkatesh, James A Totterdell, Grace M McPhee, Robert K Mahar, Mark Jones, Methma Bandara, Lauren A Barina, Bhupendra K Basnet, Asha C Bowen, …

NEJM evidence, Vol.2(11), p.EVIDoa2300132

11/2023

DOI: https://doi.org/10.1056/EVIDoa2300132

PMID: 38320527

Résumé

Benzamidines

COVID-19

Guanidines - pharmacology

Humans

SARS-CoV-2

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.)

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Titre: A Randomized Trial of Nafamostat for Covid-19
Créateurs - sans rôle: Susan C Morpeth - Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
Balasubramanian Venkatesh - The George Institute for Global Health, Newtown, NSW, Australia
James A Totterdell - Faculty of Medicine and Health, The University of Sydney School of Public Health, Sydney
Grace M McPhee - Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
Robert K Mahar - Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, VIC, Australia
Mark Jones - Department of Health and Clinical Analytics, The University of Sydney School of Public Health, Sydney
Methma Bandara - Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
Lauren A Barina - Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
Bhupendra K Basnet - Department of Infectious Diseases, Perth Children's Hospital, Perth, WA, Australia
Asha C Bowen - Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, WA, Australia
Andrew J Burke - Department of Infectious Diseases, Prince Charles Hospital, Merthyr Tydfil, United Kingdom
Belinda Cochrane - Western Sydney University School of Medicine, Campbelltown, NSW, Australia
Justin T Denholm - The Royal Melbourne Hospital
Ashesh Dhungana - Department of Medicine, National Academy of Medical Sciences at Bir Hospital, Kathmandu, Nepal
Gregory J Dore - Department of Infectious Diseases, St. Vincent's Hospital, Melbourne, VIC, Australia
Ravindra Dotel - Department of Infectious Diseases, Blacktown Hospital, Blacktown, NSW, Australia
Eamon Duffy - School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
Jack Dummer - Respiratory Services, Dunedin Hospital, Dunedin, New Zealand
Hong Foo - Department of Microbiology and Infectious Diseases, NSW Health Pathology Liverpool, Liverpool, NSW, Australia
Timothy L Gilbey - Department of Medicine and Infectious Diseases, Wagga Wagga Base Hospital, Wagga Wagga, Australia
Naomi E Hammond - Royal North Shore Hospital
Bernard J Hudson - Department of Microbiology and Infectious Diseases, NSW Health Pathology, St. Leonards, St. Leonards, NSW, Australia
Vivekanand Jha - The George Institute for Global Health, Newtown, NSW, Australia
Purnima R Jevaji - Department of Research, The George Institute for Global Health, Pune, Maharashta, India
Oommen John - Prasanna School of Public Health, Manipal Academy of Higher Education, Karnataka, India
Rajesh Joshi - Department of Research, The George Institute for Global Health, Pune, Maharashta, India
Gagandeep Kang - Wellcome Trust Research Laboratory, Chartered Accountants Australia and New Zealand, Sydney
Baldeep Kaur - Critical Care Program, The George Institute for Global Health, New Town, NSW, Australia
Seungtaek Kim - Zoonotic Virus Laboratory, Institut Pasteur Korea, Bundang-gu, Gyeonggi-do, Republic of Korea
Santa Kumar Das - Department of Internal Medicine, Maharajgunj Medical Campus, Institute of Medicine, Maharajgunj, Nepal
Jillian S Y Lau - Department of Infectious Diseases, Eastern Health, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
Roberta Littleford - UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Queensland, QLD, Australia
Julie A Marsh - Centre for Child Health Research, University of Western Australia Medical School, Nedlands, WA, Australia
Ian C Marschner - NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney
Gail Matthews - Therapeutic and Vaccine Research Program, The Kirby Institute at The University of New South Wales, Kensington, NSW, Australia
Michael J Maze - Department of Medicine, University of Otago Christchurch, Christchurch, New England
Colin J McArthur - Department of Critical Care Medicine, Te Whatu Ora - Health New Zealand, Wellington, New Zealand
James D McFadyen - Atherothrombosis and Vascular Biology Program, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
James H McMahon - Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia
Zoe K McQuilten - School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
James Molton - Department of Infectious Diseases, Western Health, Footscray, VIC, Australia
Jocelyn M Mora - Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
Vijaybabu Mudaliar - Department of Research, The George Institute for Global Health, Pune, Maharashta, India
Vi Nguyen - Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
Matthew V N O'Sullivan - Faculty of Medicine and Health, University of Sydney Westmead Clinical School, Sydney
Suman Pant - Department of Internal Medicine, Maharajgunj Medical Campus, Institute of Medicine, Maharajgunj, Nepal
Jaha E Park - Business Development Team, Chong Kun Dang Pharmaceutical Corp., Dongbaekjukjeon-daero, Giheung-gu Yongin, Kyeonggi-do, Republic of Korea
David L Paterson - Saw Swee Hock School of Public Health, National Institute of Singapore, Singapore
David J Price - Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
Nigel Raymond - Department of Medicine, Wellington School of Medicine, University of Otago, Wellington, New Zealand
Megan A Rees - Department of Respiratory and Sleep Medicine, The Royal Melbourne Hospital, Melbourne, VIC, Australia
James O Robinson - Department of Microbiology, PathWest Laboratory Medicine, Nedlands, WA, Australia
Benjamin A Rogers - Department of Infectious Diseases, Monash Health, Clayton, VIC, Australia
Wang-Shick Ryu - Virology, Institute Pasteur Korea, Bundang-gu, Gyeonggi-do, Republic of Korea
Joe Sasadeusz - Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, VIC, Australia
Omar Shum - Graduate School of Medicine, University of Wollongong, Wollonngong, NSW, Australia
Thomas L Snelling - Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, WA, Australia
Christine Sommerville - Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
Nanette Trask - Chartered Accountants Australia and New Zealand, Sydney
Sharon R Lewin - Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia
Thomas E Hills - Department of Infectious Diseases, Auckland City Hospital, Auckland, New Zealand
Joshua S Davis - Global and Tropical Health Division, Menzies School of Health Research, Darwin, NT, Australia
Jason A Roberts - Division of Anaesthesiology, Critical Care Emergency and Pain Medicine, Nîmes University Hospital at The University of Montpellier, Nîmes, France
Steven Y C Tong - Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, VIC, Australia
Détails de publication: NEJM evidence, Vol.2(11), p.EVIDoa2300132
Identifiants: 99155042009311
Unité académique: Initial MAnagement & prevent of acute orGan failures IN critically ill patiEnts - IMAGINE
Langue: English
Type de ressource: Journal article