Nafamostat Mesilate for Prevention of Post-ERCP Pancreatitis
Background: Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP. Efforts have been made to identify pharmacologic agents capable of reducing its incidence and severity. The aim of this study was to assess the efficacy of prophylactic nafamostat mesilate, a synthetic protease inhibitor, for prevention of post-ERCP pancreatitis. We had presented our data of this study at DDW2007. Additionally, the more patients were additionally enrolled to this study thereafter. Methods: A prospective, double-blind, placebo-controlled trial was conducted in 273 patients who underwent ERCP. Patients were randomized to receive nafamostat or placebo. The nafamostat group was treated with a continuous intravenous infusion of 50 mg nafamostat dissolved in 500 mL of 5% dextrose solution, starting 60 minutes before ERCP and continuing for 6 hours afterward. The placebo group patients were treated only with 500 mL of 5% dextrose solution also starting 60 minutes before ERCP and continuing for 6 hours afterward. Patients were clinically evaluated, and serum amylase levels were determined before ERCP and at 6, 12 and 24 hours thereafter. Standardized criteria were used to diagnose and to grade the severity of post-ERCP pancreatitis. Results: A total of 273 patients were included in the analysis. The groups were similar with regard to patient demographics, and to patient and procedure risk factors for post-ERCP pancreatitis. The frequency of hyperamylasemia was not significantly different between two groups. The overall incidence of post-ERCP acute pancreatitis was 6.2% (17/273). The frequency of acute pancreatitis was lower in the nafamostat vs. the placebo group (p = 0.05): nafamostat group, 5/143 (3.4%), of which 4/143 (2.7%) were graded as mild and 1/143 (0.6%) as moderate, vs. placebo group, 12/130 (9.2%), of which 9/130 (6.9%) were graded as mild and 3/130 (2.3%) as moderate. Conclusions: Prophylactic treatment with nafamostat mesilate decreases the frequency of post-ERCP pancreatitis. Further studies involving a large number of patients are needed to verify these observations of our study.