Evaluation of recombinant platelet-activating factor acetylhydrolase for reducing the incidence and severity of post-ERCP acute pancreatitis

摘要

Background: Pancreatitis is the most common major complication of diagnostic and therapeutic ERCR Platelet-activating factor (PAF) has been implicated in the pathophysiologic events associated with acute pancreatitis. Animal and human studies suggested that recombinant PAF acetylhydrolase (rPAF-AH) might ameliorate the severity of acute pancreatitis.Objective: Our purpose was to determine whether prophylactic rPAF-AH administration reduces the frequency or severity of post-ERCP pancreatitis in high-risk patients.Design: Randomized, multicenter, double-blind, placebo-controlled study.Interventions: Patients received rPAF-AH at a dose of either 1 or 5 mg/kg or placebo. Patients were administered a single intravenous infusion over 10 minutes of study drug or placebo < 1 hour before ERCP.Main Outcome Measurements: Standardized criteria were used to diagnose and grade the severity of post-ERCP pancreatitis. Adverse events were prospectively recorded.Results: A total of 600 patients were enrolled. There wereno statistically significant differences among the treatment groups with respect to patient demographics, ERCP indications, and patient and procedure risk factors for post-ERCP pancreatitis with the following exceptions: the rPAF-AH 5 nig/kg group had significantly fewer patients younger than 40 years old and scheduled to undergo a therapeutic ERCP involving the pancreatic sphincter or duct. Post-ERCP pancreatitis occurred in 17.5%, 15-9%, and 19.6% of patients receiving rPAF-AH (1 mg/kg), rPAF-AH (5 mg/kg), and placebo, respectively (P = .59 for rPAF-AH 1 mg/kg vs placebo and P = .337 forrPAF-AH 5 mg/kg vs placebo). There was no statistically significant difference between the groups with regard to the severity of pancreatitis, frequency of amylase/lipase elevation more than 3 times normal, or abdominal pain.Conclusions: There was no apparent benefit of rPAF-AH treatment compared with placebo in reducing the incidence of post-ERCP pancreatitis in subjects at increased risk.