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

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 GuoQin Tao, Kaichun Wu, Yanglin Pan, Xuegang Guo, Daiming Fan

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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.

FINDINGS: 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%]).

INTERPRETATION: 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.

FUNDING: National Key Technology R&D Program, National Natural Science Foundation of China.

Original languageEnglish (US)
Pages (from-to)2293-2301
Number of pages9
JournalThe Lancet
Volume387
Issue number10035
DOIs
StatePublished - Jun 4 2016

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Endoscopic Retrograde Cholangiopancreatography
Indomethacin
Pancreatitis
Randomized Controlled Trials
Rectal Administration
China
Hemorrhage
Natural Science Disciplines
Intention to Treat Analysis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Luo, Hui; Zhao, Lina; Leung, Joseph; Zhang, Rongchun; Liu, Zhiguo; Wang, Xiangping; Wang, Biaoluo; Nie, Zhanguo; Lei, Ting; Li, Xun; Zhou, Wence; Zhang, Lingen; Wang, Qi; Li, Ming; Zhou, Yi; Liu, Qian; Sun, Hao; Wang, Zheng; Liang, Shuhui; Guo, Xiaoyang; Tao, Qin; Wu, Kaichun; Pan, Yanglin; Guo, Xuegang; Fan, Daiming.

In: The Lancet, Vol. 387, No. 10035, 04.06.2016, p. 2293-2301.

Research output: Contribution to journalArticle

Luo, H, Zhao, L, Leung, J, Zhang, R, Liu, Z, Wang, X, Wang, B, Nie, Z, Lei, T, Li, X, Zhou, W, Zhang, L, Wang, Q, Li, M, Zhou, Y, Liu, Q, Sun, H, Wang, Z, Liang, S, Guo, X, Tao, Q, Wu, K, Pan, Y, Guo, X & Fan, D 2016, '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', The Lancet, vol. 387, no. 10035, pp. 2293-2301. https://doi.org/10.1016/S0140-6736(16)30310-5
Luo, Hui ; Zhao, Lina ; Leung, Joseph ; Zhang, Rongchun ; Liu, Zhiguo ; Wang, Xiangping ; Wang, Biaoluo ; Nie, Zhanguo ; Lei, Ting ; Li, Xun ; Zhou, Wence ; Zhang, Lingen ; Wang, Qi ; Li, Ming ; Zhou, Yi ; Liu, Qian ; Sun, Hao ; Wang, Zheng ; Liang, Shuhui ; Guo, Xiaoyang ; Tao, Qin ; Wu, Kaichun ; Pan, Yanglin ; Guo, Xuegang ; Fan, Daiming. / 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. In: The Lancet. 2016 ; Vol. 387, No. 10035. pp. 2293-2301.
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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.FINDINGS: 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{\%}]).INTERPRETATION: 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.FUNDING: National Key Technology R&D Program, National Natural Science Foundation of China.",
author = "Hui Luo and Lina Zhao and Joseph Leung and Rongchun Zhang and Zhiguo Liu and Xiangping Wang and Biaoluo Wang and Zhanguo Nie and Ting Lei and Xun Li and Wence Zhou and Lingen Zhang and Qi Wang and Ming Li and Yi Zhou and Qian Liu and Hao Sun and Zheng Wang and Shuhui Liang and Xiaoyang Guo and Qin Tao and Kaichun Wu and Yanglin Pan and Xuegang Guo and Daiming Fan",
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doi = "10.1016/S0140-6736(16)30310-5",
language = "English (US)",
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pages = "2293--2301",
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TY - JOUR

T1 - Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography

T2 - a multicentre, single-blinded, randomised controlled trial

AU - Luo, Hui

AU - Zhao, Lina

AU - Leung, Joseph

AU - Zhang, Rongchun

AU - Liu, Zhiguo

AU - Wang, Xiangping

AU - Wang, Biaoluo

AU - Nie, Zhanguo

AU - Lei, Ting

AU - Li, Xun

AU - Zhou, Wence

AU - Zhang, Lingen

AU - Wang, Qi

AU - Li, Ming

AU - Zhou, Yi

AU - Liu, Qian

AU - Sun, Hao

AU - Wang, Zheng

AU - Liang, Shuhui

AU - Guo, Xiaoyang

AU - Tao, Qin

AU - Wu, Kaichun

AU - Pan, Yanglin

AU - Guo, Xuegang

AU - Fan, Daiming

PY - 2016/6/4

Y1 - 2016/6/4

N2 - 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.FINDINGS: 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%]).INTERPRETATION: 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.FUNDING: National Key Technology R&D Program, National Natural Science Foundation of China.

AB - 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.FINDINGS: 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%]).INTERPRETATION: 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.FUNDING: National Key Technology R&D Program, National Natural Science Foundation of China.

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