Indomethacin vs Diclofenac for Preventing PEP

June 12, 2026 updated by: Yanglin Pan, Air Force Military Medical University, China

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

4050

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100000
        • Recruiting
        • The first medical center, Chinese PLA General Hospital
        • Contact:
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China, 404100
        • Recruiting
        • The Second Affiliated Hospital of Chongqing Medical University
        • Contact:
    • Fujian
      • Xiamen, Fujian, China, 361000
        • Recruiting
        • Department of Gastroenterology, Hongai Hospital
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150000
        • Recruiting
        • Zhaolei181220@163.Com
        • Contact:
          • Lei Zhao
          • Phone Number: 86-18745143401
      • Harbin, Heilongjiang, China, 150000
        • Recruiting
        • Harbin Medical University Affiliated Fourth Hospital
        • Contact:
    • Hennan
      • Kaifeng, Hennan, China, 475000
        • Recruiting
        • Huaihe Hospital of Henan University
        • Contact:
    • Hubei
      • Wuhan, Hubei, China, 430000
        • Recruiting
        • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
      • Wuhan, Hubei, China, 430000
        • Recruiting
        • Renmin Hospital of Wuhan University
        • Contact:
    • Hunan
      • Changsha, Hunan, China, 410000
        • Not yet recruiting
        • The third xiangya hospital of Central South University
        • Contact:
    • Jilin
      • Jilin City, Jilin, China, 132000
        • Recruiting
        • Jilin Miniciple People'S Hospital
        • Contact:
    • Qinghai
      • Xining, Qinghai, China, 810000
        • Recruiting
        • Qinghai University Affiliated Hospital
        • Contact:
    • Shaanxi
      • Xi'an, Shaanxi, China, 710000
        • Recruiting
        • Xijing Hospital of Digestive Diseases
      • Xi'an, Shaanxi, China, 710000
        • Recruiting
        • 986 Hospital of Xijing Hospital
        • Contact:
      • Xi'an, Shaanxi, China, 710000
        • Recruiting
        • Second Affiliated Hospital of Xi'an Jiaotong University
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250000
        • Not yet recruiting
        • Shandong Provincial Third Hospital
        • Contact:
      • Jinan, Shandong, China, 250000
        • Recruiting
        • The 960th Hospital of the PLA
        • Contact:
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200000
        • Recruiting
        • Eastern Hepatobiliary Surgery Hospital
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310000
        • Recruiting
        • the First Affiliated Hospital, Zhejiang University School of Medicine
        • Contact:
      • Hangzhou, Zhejiang, China, 310000
      • Hangzhou, Zhejiang, China, 310000
        • Not yet recruiting
        • the second Affiliated Hospital, Zhejiang University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Indomethacin
All patients without contraindications should receive 100mg rectal indomethacin within 30mins before ERCP procedure
Drug: Indomethacin 100 MG
All patients without contraindications should receive 100mg rectal indomethacin within 30mins before ERCP procedure
Active Comparator: Diclofenac group
All patients without contraindications should receive 100mg rectal diclofenac within 30mins before ERCP procedure
Drug: Diclofenac 100mg
All patients without contraindications should receive 100mg rectal diclofenac within 30mins before ERCP procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of post-ERCP Pancreatitis
Time Frame: 30 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of mortality
Time Frame: 30 days
30 days
Rate of NSAIDs-related complications
Time Frame: 30 days
NSAIDs-related complications include: acute kidney injury, allergic reaction, gastrointestinal bleeding, myocardial infarction, cerebrovascular accident, and death
30 days
Rate of mild, moderate or severe PEP
Time Frame: 30 days
The severity classification of post-ERCP pancreatitis was defined according to the Cotton Criteria. Mild PEP: with an extension of hospitalization period of 2-3 days; Moderate PEP: with an extension of hospitalization period of 4-10 days; Severe PEP: with an extension of more than 10 days, or hemorrhagic pancreatitis, phlegmon, or pseudocyst, intervention (percutaneous drainage or surgery), or death.
30 days
Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria
Time Frame: 30 days

Mild: The most common form of acute pancreatitis, without organ failure or local or systemic complications, generally resolving within 1 week of onset.

Moderately Severe: the presence of transient organ failure, local complications or exacerbation of co-morbid disease.

Severe: persistent organ failure, that is, organ failure >48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected).
30 days
Rate of ERCP-related perforation
Time Frame: 30 days
Perforation was established according to Cotton criteria, Mild: slight leakage of fluid or contrast dye, manageable through fluid administration and suction therapy ≤3 days Moderate: definite perforation required to be managed for 4-10 days Severe: management for more than 10 days or requiring for percutaneous or surgical intervention.
30 days
Rate of ERCP-related infection
Time Frame: 30 days
Infection was established according to Cotton criteria. Mild: temperature >38℃ for 24-48h Moderate: Febrile illness requiring >3 days of hospital treatment; endoscopic or percutaneous interventions; Severe: septic shock or requiring surgery.
30 days
Rate of ERCP-related bleeding
Time Frame: 30 days
Bleeding was established according to Cotton criteria. Mild: a documented decrease in hemoglobin concentration by <3 g/L, without requiring the blood transfusion; Moderate: blood transfusion ≤4 units; without need for angiographic or surgery interventions Severe: Transfusion: ≥5 units or requiring for angiographic or surgery interventions.
30 days
The rate of total adverse events
Time Frame: 30 days
Adverse events include ERCP-related or non ERCP-related adverse events
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Air Force Military Medical University, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

July 8, 2025

First Submitted That Met QC Criteria

July 8, 2025

First Posted (Actual)

July 17, 2025

Study Record Updates

Last Update Posted (Actual)

June 15, 2026

Last Update Submitted That Met QC Criteria

June 12, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KY20242439-F-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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