Romagnuolo Joseph, Hilsden Robert, Sandha Gurpal S, Cole Marty, Bass Syd, May Gary, Love Jonathan, Bain Vincent G, McKaigney John, Fedorak Richard N
Digestive Disease Center, Department of Medicine, Medical University of South Carolina, South Carolina 29425, USA.
Clin Gastroenterol Hepatol. 2008 Apr;6(4):465-71; quiz 371. doi: 10.1016/j.cgh.2007.12.032. Epub 2008 Mar 4.
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.
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.
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.
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.
内镜逆行胰胆管造影术（ERCP）与胰腺炎（PEP）风险相关。动物研究表明，（单剂量）别嘌醇（一种口服生物利用度高且活性代谢产物持久的黄嘌呤氧化酶抑制剂）可能降低此风险；人体研究结果存在矛盾。本研究的目的是确定别嘌醇是否能降低PEP的发生率。
在2个三级中心向9位内镜医师转诊接受ERCP的患者，根据高风险ERCP（测压或胰腺治疗）分层，随机在ERCP前60分钟口服300mg别嘌醇或相同安慰剂。主要结局（PEP）由盲法判定；胰腺炎根据Cotton共识定义，并在48小时和30天进行评估。次要结局包括严重PEP、住院时间和死亡率（无）。根据独立数据和安全监测委员会的建议，在盲法（中点）期中分析后试验终止。
我们将586名受试者随机分组，每组293人。PEP的粗发生率分别为5.5%（别嘌醇组）和4.1%（安慰剂组），（P = 0.44；差异 = 1.4%；95%置信区间，-2.1%至4.8%）。考虑分层因素，别嘌醇组PEP的Mantel-Haenszel合并风险比为1.37（95%置信区间，0.65 - 2.86）。亚组分析表明，高风险组可能有获益趋势但无统计学意义，而其余受试者可能有危害。逻辑回归分析发现，胰腺治疗、胰腺注射和既往PEP是PEP的唯一独立预测因素。
别嘌醇似乎并未降低PEP的总体风险；然而，其在高风险组的潜在获益（但对非高风险患者可能有危害）意味着需要进一步研究。
