title: Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial.
abstract: BACKGROUND
  Rectal 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Between 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%]).
  
  
  CONCLUSIONS
  Compared 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.
  
  
  BACKGROUND
  National Key Technology R&D Program, National Natural Science Foundation of China.
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Radiotherapy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Gastroenterology, Sacramento VA Medical Center, VANCHCS, Mather, and UC Davis Medical Center, Sacramento, CA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Leung
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Rongchun
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiangping
authors.initials: X
authors.lastname: Wang
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Biaoluo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Urumqi General Hospital of Lanzhou Military Region, Urumqi, China.
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Nie
authors.affiliation: Department of Gastroenterology, Urumqi General Hospital of Lanzhou Military Region, Urumqi, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.affiliation: The Second Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.affiliation: The Second Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Wence
authors.initials: W
authors.lastname: Zhou
authors.affiliation: The Second Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Lingen
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, No 451 Military Hospital, Xi'an, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, No 451 Military Hospital, Xi'an, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Liang
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Tao
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China. Electronic address: yanglinpan@hotmail.com.
authors.forename: Yanglin
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China. Electronic address: xuegangguo@gmail.com.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000208:Acute Disease; D000285:Administration, Rectal; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000379:methods*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000517:prevention & control*; D011182:Postoperative Care / Q000379:methods; D011300:Preoperative Care / Q000379:methods; D016037:Single-Blind Method; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin