title: 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.
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.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsujino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Isayama
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Nakai
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Osamu
authors.initials: O
authors.lastname: Togawa
authors.forename: Nobuo
authors.initials: N
authors.lastname: Toda
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Arizumi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kogure
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Suguru
authors.initials: S
authors.lastname: Mizuno
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yashima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagioka
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Saburo
authors.initials: S
authors.lastname: Matsubara
authors.forename: Natsuyo
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirano
authors.forename: Naoki
authors.initials: N
authors.lastname: Sasahira
authors.forename: Minoru
authors.initials: M
authors.lastname: Tada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects* / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000209:etiology / Q000517:prevention & control*; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014361:Trypsin Inhibitors; D055815:Young Adult
chemical_list: D006023:Glycoproteins; D012702:Serotonin Antagonists; D014361:Trypsin Inhibitors; D018967:Risperidone; C028665:urinastatin