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

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doi:10.1016/j.cgh.2007.12.032 Copyright © 2008 AGA Institute Published by Elsevier Ltd.

Original article—liver, pancreas, and biliary tract

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

Previously presented in abstract form at Canadian Digestive Disease Week March, 2001, Banff, Canada; American College of Gastroenterology October, 2002, Seattle, WA; and Digestive Disease Week May, 2005, Chicago, IL.

ph Romagnuolo, ‡, , , Hilsden‡, Gurpal S. Sandha§, Marty Cole‡, S.Y.D. Bass‡, May, Love‡, G. Bain§, McKaigney§ and N. Fedorak§ ‡Department of Medicine, University of Calgary, Calgary, Alberta, CanadaDigestive Disease Center, Department of Medicine, and Department of Biostatistics, Bioinformatics and Epidemiology, Medical University of South Carolina, South CarolinaDepartment of Medicine, University of Toronto, Ontario, Canada§Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Available online 4 March 2008.

Refers to:

Exam 2: Allopurinol to Prevent Pancreatitis After ERCP: A Randomized Placebo-Controlled TrialClinical Gastroenterology and Hepatology, Volume 6, Issue 4, April 2008, Page 371Romagnuolo

Refers to:

Risk of Post–Endoscopic Retrograde Cholangiopancreatography Pancreatitis and Ways to Prevent It: Old Myths, a Current Need? The Case of AllopurinolClinical Gastroenterology and Hepatology, Volume 6, Issue 4, April 2008, Pages 374-376Angelo Andriulli and Vito Annese

Background & Aims: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with a risk of pancreatitis (PEP). Animal studies suggest that (single-dose) allopurinol (xanthine oxidase inhibitor with high oral bioavailability and long-lasting active metabolites) may reduce this risk; human study results are conflicting. The aim of this study was to determine if allopurinol decreases the rate of PEP.

Methods: Patients referred for ERCP to 9 endoscopists at 2 tertiary centers were randomized to receive either allopurinol 300 mg or identical placebo orally 60 minutes before ERCP, stratified according to high-risk ERCP (manometry or pancreatic therapy). The primary outcome (PEP) was adjudicated blindly; pancreatitis was defined according to the Cotton consensus, and evaluated at 48 hours 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 = .44; difference = 1.4%; 95% confidence interval, −2.1% to 4.8%). The Mantel–Haenszel combined risk ratio for PEP with allopurinol, considering stratification, was 1.37 (95% confidence interval, 0.65–2.86). Subgroup analyses suggested nonsignificant trends toward possible benefit in the high-risk group, and possible harm for the remaining subjects. Logistic regression found pancreatic therapy, pancreatic injection, and prior PEP to be the only independent predictors of PEP.

Conclusions: 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.

Abbreviations: CI, confidence interval; DSM, data and safety monitoring; ERCP, endoscopic retrograde cholangiopancreatography; OR, odds ratio; PEP, post–endoscopic retrograde cholangiopancreatography pancreatitis; SOD, sphincter of Oddi dysfunction

Address requests for reprints to: ph Romagnuolo, MD, FRCPC, MSc, Medical University of South Carolina, 96 Jonathon Lucas Street, CSB #210, PO Box 250 327, ton, South Carolina 29425. fax: .

Clinical Gastroenterology and Hepatology