Indomethacin vs Diclofenac for Preventing PEP

Официальное название

Rectal Indomethacin Versus Diclofenac for Prevention of Post-ERCP Panceratitis (IDPPP2): A Multicenter, Double-blind, Randomized, Control Trial

Обзор

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.

Вмешательства

• Препарат Indomethacin 100 MG
  All patients without contraindications should receive 100mg rectal indomethacin within 30mins before ERCP procedure
• Препарат Diclofenac 100mg
  All patients without contraindications should receive 100mg rectal diclofenac within 30mins before ERCP procedure

Первичные конечные точки

• Rate of post-ERCP Pancreatitis [Срок оценки: 30 days]

Вторичные конечные точки (8)

• Rate of mild, moderate or severe PEP [Срок оценки: 30 days]
• Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria [Срок оценки: 30 days]
• Rate of ERCP-related perforation [Срок оценки: 30 days]
• Rate of ERCP-related infection [Срок оценки: 30 days]
• Rate of ERCP-related bleeding [Срок оценки: 30 days]
• Rate of NSAIDs-related complications [Срок оценки: 30 days]
• Rate of mortality [Срок оценки: 30 days]
• The rate of total adverse events [Срок оценки: 30 days]

Критерии участия

Критерии включения

• 18-90 years old patients with native papilla who planned to undergo ERCP

Критерии исключения

• Previous biliary sphincterotomy and papillary large balloon dilation
• Planned for placements of pancreatic duct stents (eg. pancreatic duct strictures, planned ampullectomy)
• Allergy to NSAIDs
• The administration of NSAIDs within 7 days
• Not suitable for NSAIDs administration (gastrointestinal hemorrhage within 4 weeks, renal dysfunction \[Cr >1.4mg/dl=120umol/l\]; presence of coagulopathy before the procedure)
• Acute pancreatitis within 7 days before ERCP or acute pancreatitis with obvious Pancreatic edema and peripancreatic fluid collections
• Hemodynamical instability
• Pregnancy or lactation
• Unable to give informed consent

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Китай · 20 центров

• The first medical center, Chinese PLA General Hospital — Пекин
• The Second Affiliated Hospital of Chongqing Medical University — Чунцин
• Department of Gastroenterology, Hongai Hospital — Xiamen
• Harbin Medical University Affiliated Fourth Hospital — Харбин
• Zhaolei181220@163.Com — Харбин
• Huaihe Hospital of Henan University — Kaifeng
• Renmin hospital of Wuhan University — Ухань
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Ухань
• … и ещё 12 центров

Публикации

• 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 pancreatiti PMID 34214449
• 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. PMID 31863440
• 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/g PMID 40113243
• 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-bl PMID 27133971

Идентификаторы

NCT: NCT07071441 · KY20242439-F-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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