Allopurinol to Prevent Pancreatitis After Endoscopic Retrograde Cholangiopancreatography (ERCP): A Randomized Placebo-Controlled Trial

ackground & Aims: Endoscopic retrograde cholangioancreatography (ERCP) is associated with a risk of panreatitis (PEP). Animal studies suggest that (single-dose) llopurinol (xanthine oxidase inhibitor with high oral biovailability and long-lasting active metabolites) may reduce his risk; human study results are conflicting. The aim of his study was to determine if allopurinol decreases the rate f PEP. Methods: Patients referred for ERCP to 9 endosopists at 2 tertiary centers were randomized to receive ither allopurinol 300 mg or identical placebo orally 60 inutes before ERCP, stratified according to high-risk RCP (manometry or pancreatic therapy). The primary outome (PEP) was adjudicated blindly; pancreatitis was dened according to the Cotton consensus, and evaluated at 8 hours and 30 days. Secondary outcomes included severe EP, length of stay, and mortality (nil). The trial was terinated after the blinded (midpoint) interim analysis, as ecommended by the independent data and safety monitorng committee. Results: We randomized 586 subjects, 293 o each arm. The crude PEP rates were 5.5% (allopurinol) nd 4.1% (placebo), (P .44; difference 1.4%; 95% condence interval, 2.1% to 4.8%). The Mantel–Haenszel ombined risk ratio for PEP with allopurinol, considering tratification, was 1.37 (95% confidence interval, 0.65–2.86). ubgroup analyses suggested nonsignificant trends toward ossible benefit in the high-risk group, and possible harm or the remaining subjects. Logistic regression found panreatic therapy, pancreatic injection, and prior PEP to be he only independent predictors of PEP. Conclusions: llopurinol does not appear to reduce the overall risk of EP; however, its potential benefit in the high-risk group but potential harm for non– high-risk patients) means furher study is required.