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