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ALLOPURINOL TO PREVENT PANCREATITIS AFTER ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP): FINAL RESULTS FROM A RANDOMIZED MULTI-CENTERED PLACEBO-CONTROLLED TRIAL
J Romagnuolo, R Hilsden, GS Sandha, M Cole, S Bass, G May, J Love, VG Bain, J McKaigney, RN Fedorak
Digestive Disease Center, Medical University of South Carolina, SC, USA; University of Calgary, University of Alberta, University of Toronto
BACKGROUND: ERCP is associated with a risk of pancreatitis (PEP). Animal studies suggest that a single dose of allopurinol (xanthine oxidase inhibitor with high oral bioavailability and long-lasting active metabolites) may reduce the PEP incidence, but human studies have had conflicting results.
AIM: To determine if allopurinol decreases the rate of PEP.
METHODS: Patients referred for ERCP to 9 endoscopists at 2 tertiary Canadian centers were randomized to receive either allopurinol 300 mg or identical placebo orally 60 min (±20) prior to ERCP, stratified according to high-risk ERCP (manometry or pancreatic therapy). The primary outcome (PEP) was blindly adjudicated, and pancreatitis was defined according to the Cotton consensus, and was evaluated at 48h and 30 days. Secondary outcomes included severe PEP, length of stay, and mortality (nil). The trial was terminated after the blinded (midpoint) interim analysis, as recommended by the independent data and safety monitoring committee.
RESULTS: We randomized 586 subjects, 293 to each arm. The crude PEP rates were 5.5% (allopurinol) and 4.1% (placebo), (p=0.44; difference=1.4% [95%CI: –2.1% to 4.8%]. The Mantel-Haenszel combined risk ratio for PEP with allopurinol, considering stratification, was 1.37 (95% CI: 0.65 to 2.86). Subgroup analyses suggested a possible benefit (p=0.050) in the high risk group, and possible harm (p=0.017) for the remaining subjects. Logistic regression found pancreatic therapy, pancreatic injection, and prior PEP to be the only independent predictors of outcome.
CONCLUSION: Allopurinol does not appear to reduce the overall risk of PEP; however, its potential benefit in the high-risk group (but potential harm for non-high-risk patients) means further study is required.
Sponsored by a CAG/CIHR Young Investigator Award