Results of the Tokyo trial of prevention of post-ERCP pancreatitis with risperidone-2: a multicenter, randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Our previous study suggested that a combination of ulinastatin and risperidone reduced post-ERCP pancreatitis (PEP) compared with ulinastatin alone.

OBJECTIVE: The aim of this study was to evaluate the efficacy of risperidone alone for prevention of PEP.

DESIGN: A multicenter, randomized, placebo-controlled, double-blind clinical trial.

SETTING: Two academic hospitals and 5 referral hospitals in Tokyo and Saitama, Japan.

PATIENTS: Patients undergoing therapeutic or interventional-diagnostic ERCP.

INTERVENTION: The patients were randomized to receive 2 mg of oral risperidone or oral placebo at 0.5 to 2 hours before ERCP.

MAIN OUTCOME MEASUREMENTS: The primary endpoint was the incidence of PEP. Secondary endpoints were the incidence of hyperenzymemia and enzyme levels (amylase, pancreatic amylase, lipase). Risk factors for PEP were evaluated.

RESULTS: We initially enrolled 500 patients in the study (250 in the risperidone group and 250 in the placebo group), but 17 (11 in the risperidone and 6 in the placebo group) were excluded after randomization. PEP developed in 24 patients (10.0%) in the risperidone group and 21 patients (8.6%) in the placebo group (P = .587). Serum amylase levels at 3 hours after ERCP were lower in the risperidone group (P = .007 in a single test of hypothesis, significance removed by Bonferroni correction for multiple testing). In multivariate analysis, a small papilla of Vater, total procedure time ≥40 minutes, and stenosis of the intrahepatic duct were significantly associated with PEP.

LIMITATIONS: Multiplicity of study centers and a relatively wide time range of drug administration time.

CONCLUSION: Risperidone did not show a benefit in prevention of PEP in this trial. (

CLINICAL TRIAL REGISTRATION NUMBER: NCT000004592.).