Indomethacin vs Diclofenac for Preventing PEP

NCT07071441 | Recruiting DMC

• 1 other identifier: KY20242439-F-1
• Study Type: interventional
• Target: 4,050
• Locations: 1 country
• Sites: 20

Brief 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.

Conditions

ERCP; Pancreatitis; Non-steroidal Anti-inflammatory (NSAID); Indomethacin; Diclofenac

Outcome Measures

Primary Outcomes (1)

• Rate of post-ERCP Pancreatitis

  a new or aggravated upper abdominal pain, with an elevated pancreatic enzyme of at least 3 times as the upper limit of normal value 24h after procedure and prolonged hospitalization days for at least 2 days. This definition was based on a widely recognized Cotton consensus

  30 days

Secondary Outcomes (8)

• Rate of mild, moderate or severe PEP

  30 days

• Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria

  30 days

• Rate of ERCP-related perforation

  30 days

• Rate of ERCP-related infection

  30 days

• Rate of ERCP-related bleeding

  30 days

Study Arms (2)

Indomethacin

EXPERIMENTAL

All patients without contraindications should receive 100mg rectal indomethacin within 30mins before ERCP procedure

Drug: Indomethacin 100 MG

Diclofenac group

ACTIVE COMPARATOR

All patients without contraindications should receive 100mg rectal diclofenac within 30mins before ERCP procedure

Drug: Diclofenac 100mg

Interventions

Indomethacin 100 MG DRUG

All patients without contraindications should receive 100mg rectal indomethacin within 30mins before ERCP procedure

Indomethacin

Diclofenac 100mg DRUG

All patients without contraindications should receive 100mg rectal diclofenac within 30mins before ERCP procedure

Diclofenac group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (20)

The first medical center, Chinese PLA General Hospital

Beijing, Beijing Municipality, 100000, China

RECRUITING

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 404100, China

RECRUITING

Department of Gastroenterology, Hongai Hospital

Xiamen, Fujian, 361000, China

RECRUITING

Harbin Medical University Affiliated Fourth Hospital

Harbin, Heilongjiang, 150000, China

RECRUITING

Zhaolei181220@163.Com

Harbin, Heilongjiang, 150000, China

RECRUITING

Huaihe Hospital of Henan University

Kaifeng, Hennan, 475000, China

RECRUITING

Renmin hospital of Wuhan University

Wuhan, Hubei, 430000, China

RECRUITING

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410000, China

NOT YET RECRUITING

Jilin Miniciple People'S Hospital

Jilin, Jilin, 132000, China

RECRUITING

Qinghai University Affiliated Hospital

Xining, Qinghai, 810000, China

NOT YET RECRUITING

986 Hospital of Xijing Hospital

Xi'an, Shaanxi, 710000, China

RECRUITING

Second Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710000, China

RECRUITING

Xijing Hospital of Digestive Diseases

Xi'an, Shaanxi, 710000, China

RECRUITING

Shandong Provincial Third Hospital

Jinan, Shandong, 250000, China

NOT YET RECRUITING

The 960th Hospital of the PLA

Jinan, Shandong, 250000, China

RECRUITING

Eastern Hepatobiliary Surgery Hospital

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Affiliated Hangzhou First People's Hospital

Hangzhou, Zhejiang, 310000, China

NOT YET RECRUITING

the First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

the second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

NOT YET RECRUITING

Related Publications (4)

• 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.

  PMID: 34214449 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.

  PMID: 31863440 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.

  PMID: 40113243 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.

  PMID: 27133971 BACKGROUND

MeSH Terms

Conditions

Pancreatitis

Interventions

Indomethacin; Diclofenac

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Central Study Contacts

Yanglin Pan, MD

CONTACT

86-84771536; yanglinpan@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: July 17, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-12

Locations

CN (20)