Does nafamostat reduce death in COVID-19 patients? Study sheds light
Australia: The researchers found a 93% posterior probability that nafamostat reduced the odds of death or organ support among hospitalized patients with COVID-19. The findings from the study were published online in NEJM Evidence on October 18, 2023.
Nafamostat mesylate is a potent in vitro antiviral agent that inhibits the host transmembrane protease serine 2 enzyme used for cell entry by the severe acute respiratory syndrome coronavirus 2. Steven Y.C. Tong, Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, VIC, Australia, and colleagues conducted an open-label, pragmatic, randomized clinical trial in New Zealand, Australia, and Nepal.
The trial included noncritically ill hospitalized patients with coronavirus disease 2019 (COVID-19). They were randomly assigned to usual care or usual care plus nafamostat.
The primary endpoint of the study was death (any cause) or receipt of new noninvasive or invasive ventilation or vasopressor support within 28 days after randomization. Analysis was performed with a Bayesian logistic model in which an adjusted odds ratio <1.0 indicates improved outcomes with nafamostat. Enrollment was closed due to the decreasing number of eligible patients.
The study led to the following findings:
- Of 647 patients screened in 21 hospitals (15 in Australia, 4 in New Zealand, and 2 in Nepal), 160 participants were enrolled from May 2021 to August 2022.
- In the intention-to-treat population, the primary endpoint occurred in 11% of 73 patients with usual care and 5% of 82 with nafamostat.
- The median adjusted odds ratio for the primary endpoint for nafamostat was 0.40 with a posterior probability of effectiveness (adjusted odds ratio <1.0) of 93%.
- For usual care compared with nafamostat, hyperkalemia occurred in 1% of 67 and 9% of 78 participants, respectively, and clinically relevant bleeding occurred in 1% of 73 and 8% of 82 participants.
"There was a 93% posterior probability that nafamostat reduced the odds of death or organ support in hospitalized patients with COVID-19," the researchers wrote. "Prespecified stopping criteria were not met, precluding definitive conclusions."
Bleeding and hyperkalemia were more common with nafamostat.
Reference:
The study titled, "A Randomized Trial of Nafamostat for Covid-19," was published in NEJM Evidence. DOI: 10.1056/EVIDoa2300132
