A Randomized Trial of Nafamostat for Covid-19
Ph.D Susan C Morpeth, M.D Balasubramanian Venkatesh, James A Totterdell, Ph.D Grace M Mcphee, Ph.D Robert K Mahar, Mark Jones, Methma Bandara, Lauren A Barina, M.D Bhupendra K Basnet, Ph.D Asha C Bowen, M.B.B.S Andrew J Burke, M.D Belinda Cochrane, Ph.D Justin T Denholm, M.D Ashesh Dhungana, Ph.D Gregory J Dore, M.B.B.S Ravindra Dotel, B.Pharm Eamon Duffy, Ph.D Jack Dummer, M.B.B.S Hong Foo, M.B.B.S Timothy L Gilbey, Ph.D Naomi E Hammond, M.D Bernard J Hudson, M.D Vivekanand Jha, M.D Purnima R Jevaji, M.D Oommen John, B.H.M.S Rajesh Joshi, Ph.D Gagandeep Kang, M.I.S Baldeep Kaur, Ph.D Seungtaek Kim, M.D Santa Kumar Das, Ph.D Jillian S Y Lau, Ph.D Roberta Littleford, Ph.D Julie A Marsh, Ph.D Ian C Marschner, M.D Gail Matthews, Ph.D Michael J Maze, M.B.Ch.B Colin J Mcarthur, M.B.B.S James D Mcfadyen, Ph.D James H Mcmahon, Ph.D Zoe K Mcquilten, M.B.B.S James Molton, M.Sc Jocelyn M Mora, M.Sc Vijaybabu Mudaliar, Vi Nguyen, Matthew V N O’sullivan, Suman Pant, Jaha E Park, M.B.B.S David L Paterson, Ph.D David J Price, M.B.Ch.B Nigel Raymond, Ph.D Megan A Rees, M.D James O Robinson, Ph.D Benjamin A Rogers, Ph.D Wang-Shick Ryu, Ph.D Joe Sasadeusz, M.Sc Omar Shum, Ph.D Thomas L Snelling, Christine Sommerville, Grad.Dip.C Nanette A Trask, Ph.D Sharon R Lewin, Thomas E Hills, Ph.D Joshua S Davis, Ph.D Jason A Roberts, Ph.D Steven Y C Tong
NEJM Evidence, doi:10.1056/evidoa2300132
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
The funding bodies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Author disclosures and other supplementary materials are available at evidence.nejm.org. The data-sharing statement is provided in the Supplementary Appendix. cine, Nîmes University Hospital at The University of Montpellier, Nîmes, France
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