Indomethacin vs Diclofenac for Preventing PEP

Summary

Pancreatitis is the most common and serious complication following post-endoscopic retrograde cholangiopancreatography (ERCP) and is associated with occasional mortality, extended hospital stays, and increased healthcare expenses. Preprocedural administration of rectal non-steroidal anti-inflammatory drugs (NSAIDs) was demonstrated to be an effective and convenient strategy for post-ERCP pancreatitis (PEP). Furthermore, several meta-analyses found that only 100mg indomethacin and diclofenac could effectively reduce PEP. Therefore, updated international clinical practice guidelines uniformly recommended administration of 100mg indomethacin or diclofenac in patients without contradictions. However, it was unclear which one of the two drug is more superior. A recent meta-analysis suggested 100mg rectal diclofenac was more efficacious than same-dose rectal indomethacin in PEP prevention (relative risk (RR) 0·59, 95% confidence intervals (CI) 0·40-0·89). Based on the results, we conducted a multicenter, double-blind, control trial to investigate whether 100mg diclofenac is superior than same-dose indomethacin. This trial planned to enroll 3612 patients in total. However, in the first interim analysis, PEP occurred in 53 patients (8.8%) of 600 patients allocated to diclofenac group and 37 patients (6.1%) of 604 patients allocated to indomethacin group (relative risk (RR) 1.44; 95% confidence interval (CI) 0.96-2.16, p=0.074). Thus, the trial was stopped according to the futility rule of conditional power. However, it was worth noticing that PEP tended to be higher in diclofenac group than that in indomethacin group. A sample size of 1204 was under power to draw the conclusion of significantly lower PEP rate in indomethacin group and thus a new trial with larger sample size of sufficient power is predicted to prove the superiority of indomethacin over diclofenac. Here we conducted a multicenter, randomized, double-blind trial to investigate whether 100mg indomethacin is superior to 100mg diclofenac in preventing PEP.

Timeline

Start

2025-06-01

Primary completion

2026-12-31

Completion

2026-12-31

Publications

• Background Akshintala VS, Sperna Weiland CJ, Bhullar FA, Kamal A, Kanthasamy K, Kuo A, Tomasetti C, Gurakar M, Drenth JPH, Yadav D, Elmunzer BJ, Reddy DN, Goenka MK, Kochhar R, Kalloo AN, Khashab MA, van Geenen EJM, Singh VK. Non-steroidal anti-inflammatory drugs, intravenous fluids, pancreatic stents, or their combinations for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2021 Sep;6(9):733-742. doi: 10.1016/S2468-1253(21)00170-9. Epub 2021 Jun 30.
• Background Dumonceau JM, Kapral C, Aabakken L, Papanikolaou IS, Tringali A, Vanbiervliet G, Beyna T, Dinis-Ribeiro M, Hritz I, Mariani A, Paspatis G, Radaelli F, Lakhtakia S, Veitch AM, van Hooft JE. ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2020 Feb;52(2):127-149. doi: 10.1055/a-1075-4080. Epub 2019 Dec 20.
• Background Kang X, Xia M, Wang J, Wang X, Luo H, Qin W, Liang Z, Zhao G, Yang L, Sun H, Tao J, Ning B, Zhong L, Zhang R, Ma X, Zhao J, Yue L, Jin H, Kang C, Ren G, Liang S, Wang H, Wang L, Nie Y, Wu K, Fan DM, Pan Y. Rectal diclofenac versus indomethacin for prevention of post-ERCP pancreatitis (DIPPP): a multicentre, double-blind, randomised, controlled trial. Gut. 2025 Jun 6;74(7):1094-1102. doi: 10.1136/gutjnl-2024-334466.
• Background 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. 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. Lancet. 2016 Jun 4;387(10035):2293-2301. doi: 10.1016/S0140-6736(16)30310-5. Epub 2016 Apr 28.

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