Back to Search Start Over

A Randomized Trial of Nafamostat for Covid-19.

Authors :
Morpeth SC
Venkatesh B
Totterdell JA
McPhee GM
Mahar RK
Jones M
Bandara M
Barina LA
Basnet BK
Bowen AC
Burke AJ
Cochrane B
Denholm JT
Dhungana A
Dore GJ
Dotel R
Duffy E
Dummer J
Foo H
Gilbey TL
Hammond NE
Hudson BJ
Jha V
Jevaji PR
John O
Joshi R
Kang G
Kaur B
Kim S
Das SK
Lau JSY
Littleford R
Marsh JA
Marschner IC
Matthews G
Maze MJ
McArthur CJ
McFadyen JD
McMahon JH
McQuilten ZK
Molton J
Mora JM
Mudaliar V
Nguyen V
O'Sullivan MVN
Pant S
Park JE
Paterson DL
Price DJ
Raymond N
Rees MA
Robinson JO
Rogers BA
Ryu WS
Sasadeusz J
Shum O
Snelling TL
Sommerville C
Trask N
Lewin SR
Hills TE
Davis JS
Roberts JA
Tong SYC
Source :
NEJM evidence [NEJM Evid] 2023 Nov; Vol. 2 (11), pp. EVIDoa2300132. Date of Electronic Publication: 2023 Oct 18.
Publication Year :
2023

Abstract

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.)

Details

Language :
English
ISSN :
2766-5526
Volume :
2
Issue :
11
Database :
MEDLINE
Journal :
NEJM evidence
Publication Type :
Academic Journal
Accession number :
38320527
Full Text :
https://doi.org/10.1056/EVIDoa2300132