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.
Clin Microbiol Infect
; 30(6): 743-754, 2024 Jun.
Article
de En
| MEDLINE
| ID: mdl-38331253
ABSTRACT
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, ANDPARTICIPANTS:
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.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Benzamidines
/
Serine endopeptidases
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Essais contrôlés randomisés comme sujet
/
Inhibiteurs de la sérine protéinase
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SARS-CoV-2
/
Traitements médicamenteux de la COVID-19
/
Guanidines
Type d'étude:
Clinical_trials
/
Guideline
/
Prognostic_studies
/
Systematic_reviews
Limites:
Adult
/
Humans
Langue:
En
Journal:
Clin Microbiol Infect
Sujet du journal:
DOENCAS TRANSMISSIVEIS
/
MICROBIOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Australie
Pays de publication:
Royaume-Uni