The results of the Tokyo trial of prevention of post-ERCP pancreatitis with risperidone (Tokyo P3R): a multicenter, randomized, phase II, non-placebo-controlled trial.

backgroundA previous study suggested that ulinastatin effectively prevented post-ERCP pancreatitis (PEP) and hyperenzymemia (PEH) in patients at average risk. In experimental models, risperidone, a selective serotonin 2A antagonist, ameliorated acute pancreatitis. We assessed the effect of risperidone combined with ulinastatin for the prevention of PEP in high-risk patients.

methodsIn a multicenter, randomized, controlled, phase II trial, patients undergoing therapeutic ERCP were randomly assigned to receive ulinastatin (150000 U) with or without risperidone (1 mg). A risperidone tablet was taken orally 30-60 min before ERCP and ulinastatin was administered intravenously for 10 min immediately prior to ERCP. The primary end point was the incidence of PEP; secondary end points were PEH severity and enzyme levels (amylase, pancreatic amylase, lipase).

resultsA total of 226 patients (113 per group) were included in the study. Six patients in the risperidone + ulinastatin group and ten patients in the ulinastatin group developed pancreatitis (5.3 vs. 8.8 %, p = 0.438). The incidence of moderate/severe PEP was lower in the risperidone + ulinastatin group (1.8 %) than in the ulinastatin group (4.4 %), but this difference was not significant. Although the incidence of PEH did not differ significantly, post-ERCP levels of all pancreatic enzymes were significantly lower in the risperidone + ulinastatin group.

conclusionsProphylactic oral risperidone administration in combination with ulinastatin did not reduce the incidence and severity of PEP in high-risk patients as compared with ulinastatin alone. However, risperidone showed an additive effect with ulinastatin, reducing serum pancreatic enzyme levels.