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

A Randomized Trial of Nafamostat for Covid-19

NEJM Evid. 2023 Nov;2(11):EVIDoa2300132. doi: 10.1056/EVIDoa2300132. Epub 2023 Oct 18.

Authors

Susan C Morpeth^{1

2}, Balasubramanian Venkatesh^{3

4

5}, James A Totterdell⁶, Grace M McPhee⁷, Robert K Mahar^{8

9}, Mark Jones¹⁰, Methma Bandara⁷, Lauren A Barina⁷, Bhupendra K Basnet^{11

12}, Asha C Bowen¹³, Andrew J Burke^{14

15}, Belinda Cochrane^{16

17}, Justin T Denholm^{7

18}, Ashesh Dhungana¹⁹, Gregory J Dore^{20

21}, Ravindra Dotel²², Eamon Duffy^{23

24}, Jack Dummer^{25

26}, Hong Foo²⁷, Timothy L Gilbey²⁸, Naomi E Hammond^{29

30

31}, Bernard J Hudson³², Vivekanand Jha⁵, Purnima R Jevaji³³, Oommen John^{34

35}, Rajesh Joshi³³, Gagandeep Kang³⁶, Baldeep Kaur²⁹, Seungtaek Kim³⁷, Santa Kumar Das³⁸, Jillian S Y Lau³⁹, Roberta Littleford⁴⁰, Julie A Marsh^{13

41}, Ian C Marschner⁴², Gail Matthews^{43

44}, Michael J Maze⁴⁵, Colin J McArthur⁴⁶, James D McFadyen^{47

48}, James H McMahon⁴⁹, Zoe K McQuilten^{50

51}, James Molton⁵², Jocelyn M Mora⁷, Vijaybabu Mudaliar³³, Vi Nguyen⁷, Matthew V N O'Sullivan^{53

54}, Suman Pant³⁸, Jaha E Park⁵⁵, David L Paterson⁵⁶, David J Price^{7

8}, Nigel Raymond^{57

58}, Megan A Rees⁵⁹, James O Robinson^{60

61}, Benjamin A Rogers^{62

63}, Wang-Shick Ryu⁶⁴, Joe Sasadeusz¹⁸, Omar Shum^{65

66}, Thomas L Snelling^{6

13}, Christine Sommerville⁷, Nanette Trask⁶⁷, Sharon R Lewin^{7

18

49}, Thomas E Hills^{68

69}, Joshua S Davis^{70

71}, Jason A Roberts^{72

73

74

75}, Steven Y C Tong^{7

18}

Affiliations

¹ Department of Microbiology and Infectious Diseases, Middlemore Hospital, Te Whatu Ora Counties Makukau, Auckland, New Zealand.
² Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
³ Department of Intensive Care Medicine, The University of Queensland at Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
⁴ Department of Intensive Care Medicine, The University of Queensland at The Wesley Hospital, Toowong, QLD, Australia.
⁵ The George Institute for Global Health, Newtown, NSW, Australia.
⁶ Faculty of Medicine and Health, The University of Sydney School of Public Health, Sydney.
⁷ Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
⁸ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.
⁹ Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, VIC, Australia.
¹⁰ Department of Health and Clinical Analytics, The University of Sydney School of Public Health, Sydney.
¹¹ Department of Medicine, Bir Hospital, Kathmandu, Nepal.
¹² Department of Infectious Diseases, Perth Children's Hospital, Perth, WA, Australia.
¹³ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, WA, Australia.
¹⁴ Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.
¹⁵ Department of Infectious Diseases, Prince Charles Hospital, Merthyr Tydfil, United Kingdom.
¹⁶ Department of Respiratory and Sleep Medicine, Campbelltown Hospital, Campbelltown, NSW, Australia.
¹⁷ Western Sydney University School of Medicine, Campbelltown, NSW, Australia.
¹⁸ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, VIC, Australia.
¹⁹ Department of Medicine, National Academy of Medical Sciences at Bir Hospital, Kathmandu, Nepal.
²⁰ Viral Hepatitis Clinical Research Program, Kirby Institute, University of New South Wales, Kensington, NSW, Australia.
²¹ Department of Infectious Diseases, St. Vincent's Hospital, Melbourne, VIC, Australia.
²² Department of Infectious Diseases, Blacktown Hospital, Blacktown, NSW, Australia.
²³ Department of Infectious Diseases, Te Whatu Ora Health New Zealand at Auckland City Hospital, Auckland, New Zealand.
²⁴ School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
²⁵ Department of Medicine, University of Otago, Dunedin, New Zealand.
²⁶ Respiratory Services, Dunedin Hospital, Dunedin, New Zealand.
²⁷ Department of Microbiology and Infectious Diseases, NSW Health Pathology Liverpool, Liverpool, NSW, Australia.
²⁸ Department of Medicine and Infectious Diseases, Wagga Wagga Base Hospital, Wagga Wagga, Australia.
²⁹ Critical Care Program, The George Institute for Global Health, New Town, NSW, Australia.
³⁰ Critical Care Program, The University of New South Wales, Sydney.
³¹ Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St. Leonards, NSW, Australia.
³² Department of Microbiology and Infectious Diseases, NSW Health Pathology, St. Leonards, St. Leonards, NSW, Australia.
³³ Department of Research, The George Institute for Global Health, Pune, Maharashta, India.
³⁴ Department of Research, The George Institute for Global Health, Vellore, India.
³⁵ Prasanna School of Public Health, Manipal Academy of Higher Education, Karnataka, India.
³⁶ Wellcome Trust Research Laboratory, Chartered Accountants Australia and New Zealand, Sydney.
³⁷ Zoonotic Virus Laboratory, Institut Pasteur Korea, Bundang-gu, Gyeonggi-do, Republic of Korea.
³⁸ Department of Internal Medicine, Maharajgunj Medical Campus, Institute of Medicine, Maharajgunj, Nepal.
³⁹ Department of Infectious Diseases, Eastern Health, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
⁴⁰ UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Queensland, QLD, Australia.
⁴¹ Centre for Child Health Research, University of Western Australia Medical School, Nedlands, WA, Australia.
⁴² NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney.
⁴³ Department of Infectious Diseases, St. Vincent's Hospital Sydney, Sydney.
⁴⁴ Therapeutic and Vaccine Research Program, The Kirby Institute at The University of New South Wales, Kensington, NSW, Australia.
⁴⁵ Department of Medicine, University of Otago Christchurch, Christchurch, New England.
⁴⁶ Department of Critical Care Medicine, Te Whatu Ora - Health New Zealand, Wellington, New Zealand.
⁴⁷ Department of Clinical Haematology, Alfred Hospital, Melbourne, VIC, Australia.
⁴⁸ Atherothrombosis and Vascular Biology Program, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
⁴⁹ Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia.
⁵⁰ Department of Haematology, Monash Health, Melbourne, VIC, Australia.
⁵¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁵² Department of Infectious Diseases, Western Health, Footscray, VIC, Australia.
⁵³ Department of Microbiology and Infectious Diseases, NSW Health Pathology Westmead Hospital, Newcastle, NSW, Australia.
⁵⁴ Faculty of Medicine and Health, University of Sydney Westmead Clinical School, Sydney.
⁵⁵ Business Development Team, Chong Kun Dang Pharmaceutical Corp., Dongbaekjukjeon-daero, Giheung-gu Yongin, Kyeonggi-do, Republic of Korea.
⁵⁶ Saw Swee Hock School of Public Health, National Institute of Singapore, Singapore.
⁵⁷ Department of Medicine, Te Whatu Ora Health New Zealand Capital, Coast and Hutt Valley, Wellington, New Zealand.
⁵⁸ Department of Medicine, Wellington School of Medicine, University of Otago, Wellington, New Zealand.
⁵⁹ Department of Respiratory and Sleep Medicine, The Royal Melbourne Hospital, Melbourne, VIC, Australia.
⁶⁰ Department of Infectious Diseases, Royal Perth Hospital, Perth, WA, Australia.
⁶¹ Department of Microbiology, PathWest Laboratory Medicine, Nedlands, WA, Australia.
⁶² Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, VIC, Australia.
⁶³ Department of Infectious Diseases, Monash Health, Clayton, VIC, Australia.
⁶⁴ Virology, Institute Pasteur Korea, Bundang-gu, Gyeonggi-do, Republic of Korea.
⁶⁵ Department of Infectious Diseases, Wollongong Hospital, Kingoonya, NSW, Australia.
⁶⁶ Graduate School of Medicine, University of Wollongong, Wollonngong, NSW, Australia.
⁶⁷ Chartered Accountants Australia and New Zealand, Sydney.
⁶⁸ Department of Clinical Research, Medical Research Institute of New Zealand, Wellington, New Zealand.
⁶⁹ Department of Infectious Diseases, Auckland City Hospital, Auckland, New Zealand.
⁷⁰ School of Medicine and Public Health, The University of Newcastle, New Castle, Australia.
⁷¹ Global and Tropical Health Division, Menzies School of Health Research, Darwin, NT, Australia.
⁷² Faculty of Medicine, The University of Queensland Centre for Clinical Research, Herston, QLD, Australia.
⁷³ Metro North Health, Herston Infectious Diseases Institute, Herston, QLD, Australia.
⁷⁴ Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
⁷⁵ Division of Anaesthesiology, Critical Care Emergency and Pain Medicine, Nîmes University Hospital at The University of Montpellier, Nîmes, France.

PMID: 38320527
DOI: 10.1056/EVIDoa2300132

Abstract

A Randomized Trial of Nafamostat for Covid-19Nafamostat mesylate is a potent in vitro antiviral that inhibits the host transmembrane protease serine 2 enzyme used by SARS-CoV-2 for cell entry. Morpeth et al report the results of an open-label randomized clinical trial of nafamostat for noncritically ill patients with Covid-19.

Publication types

Randomized Controlled Trial

MeSH terms

Benzamidines
COVID-19*
Guanidines / pharmacology
Humans
SARS-CoV-2

Substances

nafamostat
Guanidines
Benzamidines