A Randomized Trial of Nafamostat for Covid-19

• DOI: 10.1056/evidoa2300132
• Publication Date: 2023-10-18T17:00:32Z
• Authors: Susan C. Morpeth; Balasubramanian V...; 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’Su...; 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 Sommerv...; Nanette Trask; Sharon R. Lewin; Thomas E. Hills; Joshua S. Davis; Jason A. Roberts; Steven Y.C. Tong
• Keywords: SARS-CoV-2; Humans; COVID-19; Guanidines; Benzamidines

BackgroundNafamostat mesylate is a potent in vitro antiviral agent that inhibits the host transmembrane protease serine 2 enzyme used by severe acute respiratory syndrome coronavirus for cell entry.MethodsThis open-label, pragmatic, randomized clinical trial Australia, New Zealand, and Nepal included noncritically ill hospitalized patients with disease 2019 (Covid-19). Participants were randomly assigned to usual care or plus nafamostat. The primary end point was death (any cause) receipt of new invasive noninvasive ventilation vasopressor support within 28 days after randomization. Analysis Bayesian logistic model which an adjusted odds ratio <1.0 indicates improved outcomes Enrollment closed due falling numbers eligible patients.ResultsWe screened 647 21 hospitals (15 4 Nepal) enrolled 160 participants from May 2021 August 2022. In intention-to-treat population, occurred 8 (11%) 73 (5%) 82 median nafamostat 0.40 (95% credible interval, 0.12 1.34) posterior probability effectiveness (adjusted <1.0) 93%. For compared nafamostat, hyperkalemia 1 (1%) 67 7 (9%) 78 participants, respectively, clinically relevant bleeding (8%) participants.ConclusionsAmong Covid-19, there 93% reduced organ support. Prespecified stopping criteria not met, precluding definitive conclusions. Hyperkalemia more common (Funded ASCOT others; ClinicalTrials.gov number, NCT04483960.)