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

J Gastroenterol. 2013 Aug;48(8):982-8. doi: 10.1007/s00535-012-0698-5. Epub 2012 Oct 24.

Abstract

Background: A 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.

Methods: In 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).

Results: A 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.

Conclusions: Prophylactic 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.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Cholangiopancreatography, Endoscopic Retrograde / adverse effects*
  • Cholangiopancreatography, Endoscopic Retrograde / methods
  • Drug Therapy, Combination
  • Female
  • Glycoproteins / administration & dosage
  • Glycoproteins / therapeutic use*
  • Humans
  • Incidence
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Pancreatitis / etiology
  • Pancreatitis / prevention & control*
  • Risperidone / administration & dosage
  • Risperidone / therapeutic use*
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / therapeutic use
  • Severity of Illness Index
  • Treatment Outcome
  • Trypsin Inhibitors
  • Young Adult

Substances

  • Glycoproteins
  • Serotonin Antagonists
  • Trypsin Inhibitors
  • Risperidone
  • urinastatin