Low-Dose vs Standard-Dose Indomethacin for Preventing Post-ERCP Pancreatitis

Low-Dose Versus Standard-Dose Rectal Indomethacin to Prevent Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Multicentre, Non-Inferiority, Double-Blind, Randomised, Controlled Trial

Endoscopic Retrograde Cholangiopancreatography (ERCP) is a widely used procedure for diagnosing and treating pancreatic and biliary diseases. Despite its benefits, ERCP carries a risk of post-procedure pancreatitis (PEP), which occurs in approximately 12.2% of cases and can significantly increase healthcare costs and patient morbidity. Preventing PEP is crucial for improving patient outcomes and reducing the economic burden of ERCP.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, have been shown to be effective in reducing the incidence of PEP when administered rectally before ERCP. The standard dose recommended by guidelines is 100mg, which has been associated with a significant reduction in PEP rates. However, higher doses of NSAIDs can increase the risk of adverse events, including gastrointestinal bleeding and renal impairment. Therefore, there is a need to determine whether a lower dose can provide similar benefits without increasing these risks.

This multicenter, non-inferiority, double-blind, randomized controlled trial will be conducted in China. Participants will be adults aged 18 or older scheduled for ERCP. They will be randomly assigned in a 1:1 ratio to either the low-dose (50mg) or standard-dose (100mg) indomethacin group. The intervention will be administered rectally 30 minutes before the ERCP procedure. The study will follow a double-blind design, ensuring that both patients and investigators are unaware of the treatment allocation.

The results of this trial could significantly influence clinical practice by providing evidence on the effectiveness of a lower dose of indomethacin in preventing PEP. This could lead to a reduction in the risk of adverse events associated with higher doses and potentially decrease healthcare costs without compromising patient safety. By optimizing the dosing of indomethacin, this study aims to improve the safety and cost-effectiveness of ERCP procedures.

Study Overview

• Status: Recruiting
• Conditions: Post-ERCP Pancreatitis
• Intervention / Treatment: Drug: low dose indomethacin; Drug: standard dose indomethacin

• Study Type: Interventional
• Enrollment (Estimated): 1366
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zhao-Shen Li; Email: zhaoshen-li@hotmail.com
• Study Contact Backup: Name: Liang-Hao Hu; Phone Number: +8613817593520; Email: lianghao-hu@hotmail.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Ruijin Hospital
    • Contact: Duo-Wu Zou; Phone Number: +86 13901617608
  • Shanghai, China
    • Not yet recruiting
    • Shanghai General Hospital
    • Contact: Bai-Wen Li; Phone Number: +86 18930894343
  • Shanghai, China
    • Not yet recruiting
    • Changhai Hospital
    • Contact: Zhao-Shen Li; Email: zhaoshen-li@hotmail.com
    • Contact: Liang-Hao Hu; Phone Number: +8613817593520; Email: lianghao-hu@hotmail.com
  • Zhejiang, China
    • Recruiting
    • Sir Run Run Shaw Hospital
    • Contact: Song-Mei Lou; Phone Number: +86 13958031730; Email: srrshlsm@zju.edu.cn
  • Zhejiang, China
    • Not yet recruiting
    • Affiliated Hospital of Jiaxing University
    • Contact: Hong-Kun Zhou; Phone Number: +86 13586332200
  • Zhejiang, China
    • Not yet recruiting
    • Dongyang People's Hospital
    • Contact: Bin Wang; Phone Number: +86 13857932995
  • Zhejiang, China
    • Not yet recruiting
    • First Affiliated Hospital of Ningbo University
    • Contact: Liang Yang; Phone Number: +86 13777128020
  • Zhejiang, China
    • Not yet recruiting
    • Jinhua Central Hospital
    • Contact: Xiao-Kang Wu; Phone Number: +86 13989411219
  • Zhejiang, China
    • Not yet recruiting
    • People's Hospital of Quzhou
    • Contact: Zheng-fei Wang; Phone Number: +86 13587111668
  • Zhejiang, China
    • Not yet recruiting
    • Shaoxing People's Hospital
    • Contact: Zhi-Liang Chen; Phone Number: +86 13305758802
  • Zhejiang, China
    • Not yet recruiting
    • Zhuji People's Hospital of Zhejiang Province
    • Contact: Jun Zhen; Phone Number: +86 13819522121
  • Zhejiang, China
    • Recruiting
    • Taizhou Enze Medical Center Group
    • Contact: Ai-Dong Wang; Phone Number: +86 13706766175

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 years or older.
• Patients planned to undergo Endoscopic Retrograde Cholangiopancreatography

Exclusion Criteria:

• Standard contraindications to ERCP
• Allergy to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
• Use of NSAIDs within 7 days prior to ERCP
• 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 3 days before ERCP
• Hemodynamic instability
• Pregnancy or lactation
• Patients who are unwilling or unable to provide informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low dose indomethacin; patients randomized to this intervention receive 50mg indomethacin	Drug: low dose indomethacin; Patients randomized to this intervention receive 50mg indomethacin suppositories within 30 min before ERCP.
Active Comparator: standard dose indomethacin; patients randomized to this intervention receive 100mg indomethacin	Drug: standard dose indomethacin; Patients randomized to this intervention receive 100mg indomethacin suppositories within 30 min before ERCP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Proportion of Subjects in Each Study Group With Post-ERCP Pancreatitis	Within 48 hours after ERCP

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Subjects in Each Study Group With Moderate-severe Post-ERCP Pancreatitis		Within one month of ERCP
Rate of Overall ERCP-related complications	ERCP-related complications include post-ERCP pancreatitis, gastrointestinal bleeding, perforation or infection according to Cotton Criteria.	Within one month of ERCP
Rate of ERCP-related perforation		Within one month of ERCP
Rate of ERCP-related infection		Within one month of ERCP
Rate of ERCP-related bleeding		Within one month of ERCP
Rate of NSAIDs-related complications	NSAIDs-related complications include: acute kidney injury, allergic reaction, gastrointestinal bleeding, myocardial infarction, cerebrovascular accident, and death	Within one month of ERCP

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Collaborators: Ruijin Hospital; Sir Run Run Shaw Hospital; Shaoxing People's Hospital; Jinhua Central Hospital; People's Hospital of Quzhou; Dongyang People's Hospital; Affiliated Hospital of Jiaxing University; Zhuji People's Hospital of Zhejiang Province; Shanghai General Hospital, China; First Affiliated Hospital of Ningbo University; Taizhou Enze Medical Center Group

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 19, 2025
• First Submitted That Met QC Criteria: July 19, 2025
• First Posted (Actual): July 28, 2025

Study Record Updates

• Last Update Posted (Actual): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 16, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Indomethacin
• Other Study ID Numbers: INSPIRE

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