Nafamostat Reduces the Incidence of post‐ERCP Pancreatitis: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Abstract

Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). As the management of pancreatitis is limited, clinical approaches focus on the prevention of post‐ERCP pancreatitis (PEP). In theory, the serine protease inhibitor nafamostat can reduce circulating inflammatory mediators in pancreatitis. We aimed to investigate the effect of nafamostat in the prevention of PEP in this systematic review and meta‐analysis. The protocol for this review was registered in PROSPERO (CRD42022367988). We systematically searched 5 databases without any filters on September 26, 2022. The eligible population was adult patients undergoing ERCP. We compared the PEP preventive effect of nafamostat to placebo. The main outcome was the occurrence of PEP. We calculated the pooled odds ratios (ORs), mean differences, and corresponding 95% confidence intervals (95% CIs) and multilevel model. The risk of bias was assessed using the Rob2 tool. Seven randomized controlled trials involving 2,962 patients were eligible for inclusion. Nafamostat reduced the overall incidence rate of PEP (20 mg, OR: 0.50, 95% CI: 0.30–0.82 and 50 mg, OR: 0.48, 95% CI: 0.24–0.96). However, the occurrence of mild PEP was significantly reduced only in the subgroup receiving 20 mg nafamostat (OR, 0.49, 95% CI: 0.31–0.77). Overall, nafamostat therapy reduced moderate PEP in high‐risk patients (OR: 0.18, 95% CI: 0.0.4–0.84) and mild PEP in low‐risk patients (OR: 0.32, 95% CI: 0.17–0.61). Nafamostat is an effective therapy in the prevention of mild post‐ERCP pancreatitis. Further research is required to determine the cost‐effectiveness of this therapy.