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TMPRSS2 inhibitors for the treatment of COVID-19 in adults: a systematic review and meta-analysis of randomized clinical trials of nafamostat and camostat mesylate.
- Source :
-
Clinical Microbiology & Infection . Jun2024, Vol. 30 Issue 6, p743-754. 12p. - Publication Year :
- 2024
-
Abstract
- Synthetic serine protease inhibitors block the cellular enzyme transmembrane protease serine 2, thus preventing SARS-CoV-2 cell entry. There are two relevant drugs in this class, namely, nafamostat (intravenous formulation) and camostat (oral formulation). To determine whether transmembrane protease serine 2 inhibition with nafamostat or camostat is associated with a reduced risk of 30-day all-cause mortality in adults with COVID-19. Scientific databases and clinical trial registry platforms. Preprints or published randomized clinical trials (RCTs) of nafamostat or camostat vs. usual care or placebo in adults requiring treatment for COVID-19. The primary outcome of the meta-analysis was 30-day all-cause mortality. Secondary outcomes included time to recovery, adverse events, and serious adverse events. Risk of bias (RoB) was assessed using the revised Cochrane RoB 2 tool for individually randomized trials. Meta-analysis was conducted in the R package meta (v7.0-0) using inverse variance and random effects. Protocol registration number was INPLASY202320120. Twelve RCTs were included. Overall, the number of available patients was small (nafamostat = 387; camostat = 1061), the number of enrolled patients meeting the primary outcome was low (nafamostat = 12; camostat = 13), and heterogeneity was high. In hospitalized adults, we did not identify differences in 30-day all-cause mortality (risk ratio [95% CI]: 0.58 [0.19, 1.80], p 0.34; I 2 = 0%; n = 6) and time to recovery (mean difference [95% CI]: 0.08 days [−0.74, 0.89], p 0.86; n = 2) between nafamostat vs. usual care; and for 30-day all-cause mortality (risk ratio [95% CI]: 0.99 [0.31, 3.18], p 0.99; n = 2) between camostat vs. placebo. The RCT evidence is inconclusive to determine whether there is a mortality reduction and safety with either nafamostat or camostat for the treatment of adults with COVID-19. There were high RoB, small sample size, and high heterogeneity between RCTs. [ABSTRACT FROM AUTHOR]
- Subjects :
- *COVID-19 treatment
*CLINICAL trials
*ADULTS
*SCIENCE databases
*MORTALITY
Subjects
Details
- Language :
- English
- ISSN :
- 1198743X
- Volume :
- 30
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Clinical Microbiology & Infection
- Publication Type :
- Academic Journal
- Accession number :
- 177455186
- Full Text :
- https://doi.org/10.1016/j.cmi.2024.01.029