- Title
- 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
- Creator
- Hernández-Mitre, María Patricia; Morpeth, Susan C.; Roberts, Jason A.; Venkatesh, Balasubramanian; Hills, Thomas E.; Davis, Joshua; Mahar, Robert K.; McPhee, Grace; Jones, Mark; Totterdell, James; Tong, Steven Y. C.
- Relation
- Clinical Microbiology and Infection Vol. 30, Issue 6, p. 743-754
- Publisher Link
- http://dx.doi.org/10.1016/j.cmi.2024.01.029
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2024
- Description
- Background: 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). Objective: 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. Data sources: Scientific databases and clinical trial registry platforms. Study eligibility criteria, interventions, and participants: Preprints or published randomized clinical trials (RCTs) of nafamostat or camostat vs. usual care or placebo in adults requiring treatment for COVID-19. Methods of data synthesis and risk-of-bias assessment: 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. Results: 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; I2 = 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. Conclusion: 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.
- Subject
- camostat; clinical trials; COVID-19; nafamostat; SARS-CoV-2
- Identifier
- http://hdl.handle.net/1959.13/1504159
- Identifier
- uon:55463
- Identifier
- ISSN:1198-743X
- Language
- eng
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