• Hui Luo, Lina Zhao, Joseph Leung, Rongchun Zhang, Zhiguo Liu, Xiangping Wang, Biaoluo Wang, Zhanguo Nie, Ting Lei, Xun Li, Wence Zhou, Lingen Zhang, Qi Wang, Ming Li, Yi Zhou, Qian Liu, Hao Sun, Zheng Wang, Shuhui Liang, Xiaoyang Guo, Qin Tao, Kaichun Wu, Yanglin Pan, Xuegang Guo, and Daiming Fan.
• Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
• Lancet. 2016 Jun 4; 387 (10035): 2293-2301.

BackgroundRectal indometacin decreases the occurrence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the population most at risk and the optimal timing of administration require further investigation. We aimed to assess whether pre-procedural administration of rectal indometacin in all patients is more effective than post-procedural use in only high-risk patients to prevent post-ERCP pancreatitis.MethodsWe did a multicentre, single-blinded, randomised controlled trial at six centres in China. Eligible patients with native papilla undergoing ERCP were randomly assigned in a 1:1 ratio (with a computer-generated list) to universal pre-procedural indometacin or post-procedural indometacin in only high-risk patients, with stratification by trial centres and block size of ten. In the universal indometacin group, all patients received a single dose (100 mg) of rectal indometacin within 30 min before ERCP. In the risk-stratified, post-procedural indometacin group, only patients at predicted high risk received rectal indometacin, immediately after ERCP. Investigators, but not patients, were masked to group allocation. The primary outcome was overall ocurrence of post-ERCP pancreatitis. The analysis followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT02002650.FindingsBetween Dec 15, 2013, and Sept 21, 2015, 2600 patients were randomly assigned to universal, pre-procedural indometacin (n=1297) or risk-stratified, post-procedural indometacin (n=1303). Overall, post-ERCP pancreatitis occurred in 47 (4%) of 1297 patients assigned to universal indometacin and 100 (8%) of 1303 patients assigned to risk-stratified indometacin (relative risk 0·47; 95% CI 0·34-0·66; p<0·0001). Post-ERCP pancreatitis occurred in 18 (6%) of 305 high-risk patients in the universal group and 35 (12%) of 281 high-risk patients in the risk-stratified group (p=0·0057). Post-ERCP pancreatitis was also less frequent in average-risk patients in the universal group (3% [29/992]), in which they received indometacin, than in the risk-stratified group (6% [65/1022]), in which they did not receive the drug (p=0·0003). Other than pancreatitis, adverse events occurred in 41 (3%; two severe) patients in the universal indometacin group and 48 (4%; one severe) patients in the risk-stratified group. The most common adverse events were biliary infection (22 [2%] patients vs 33 [3%] patients) and gastrointestinal bleeding (13 [1%] vs ten [1%]).InterpretationCompared with a risk-stratified, post-procedural strategy, pre-procedural administration of rectal indometacin in unselected patients reduced the overall occurrence of post-ERCP pancreatitis without increasing risk of bleeding. Our results favour the routine use of rectal indometacin in patients without contraindications before ERCP.FundingNational Key Technology R&D Program, National Natural Science Foundation of China.Copyright © 2016 Elsevier Ltd. All rights reserved.

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