BACKGROUND: Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP. 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 were no 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 mg/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 for rPAF-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.
RCT Entities:
BACKGROUND:Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP. 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 were no 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 mg/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 for rPAF-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.