Indomethacin for Biliary ERCP Patients

Indomethacin vs. no Indomethacin for Patients Undergoing Biliary ERCP With Prior Biliary Sphincterotomy

This study is a randomized clinical trial evaluating the efficacy of rectal indomethacin in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in patients undergoing biliary ERCP who have a history of prior biliary sphincterotomy. While rectal indomethacin has demonstrated benefits in preventing post-ERCP pancreatitis in high-risk patients, its utility in this specific patient subgroup remains unclear. This trial aims to determine whether prophylactic administration of indomethacin offers a measurable benefit over no intervention in this lower-risk population.

Eligible patients will be identified prior to their scheduled biliary ERCP and screened for inclusion criteria. Following informed consent, participants will be randomized to receive either rectal indomethacin or no indomethacin prior to the procedure.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatitis; Post-ERCP Acute Pancreatitis; Post-ERCP Pancreatitis; Pancreatitis Biliary; Pancreatitis Acute Biliary; Post-ERCP Adverse Events
• Intervention / Treatment: Drug: indomethacin

• Study Type: Interventional
• Enrollment (Estimated): 860
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Vu Dinh, MD, PhD; Phone Number: 7142249012; Email: Vu.Dinh@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California, San Francisco
      • Contact: Michael C Larsen, MD; Phone Number: 415-502-4444; Email: Michael.Larsen@ucsf.edu
      • Contact: Vu Dinh, MD, PhD; Email: Vu.Dinh@ucsf.edu
      • Principal Investigator: Michael C Larsen, MD
      • Sub-Investigator: Sun-Chuan Dai, MD
      • Sub-Investigator: Patrick Avila, MD, MPH
      • Sub-Investigator: Abdul Kouanda, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female ≥ 18 years of age at the time of ERCP.
2. Scheduled to undergo routine biliary ERCP with documentation of a prior biliary sphincterotomy.
3. Ability to receive rectal medication.
4. Ability and willingness to comply with all study procedures and follow-up requirements.
5. Written informed consent (and assent when applicable) was obtained from the subject or the subject's legal representative, and the subject's ability to comply with the requirements of the study was confirmed.

Exclusion Criteria:

1. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
2. Known hypersensitivity or contraindication to indomethacin, other nonsteroidal anti-inflammatory drugs, or suppository components.
3. Active gastrointestinal bleeding, history of NSAID-induced gastrointestinal ulceration, or other conditions that contraindicate NSAID use.
4. Significant renal impairment (e.g., baseline serum creatinine above institutional upper limit of normal or estimated glomerular filtration rate < 30 mL/min/1.73 m²).
5. Current use of other NSAIDs that cannot be safely discontinued per the investigator's judgment.
6. Known chronic pancreatitis
7. Presence of a condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indomethacin; Participants randomized to this arm will receive a single 100 mg rectal indomethacin suppository administered immediately prior to biliary ERCP for the prevention of post-ERCP pancreatitis.	Drug: indomethacin; Indomethacin 100 mg administered as a single rectal suppository immediately prior to biliary ERCP for the prevention of post-ERCP pancreatitis. Participants are randomized to receive the study intervention before the procedure.; Other Names: rectal indomethacin
No Intervention: Digital Rectal Exam; A routine digital rectal examination performed immediately prior to biliary ERCP without administration of prophylactic rectal indomethacin. This procedure is used as the control intervention to maintain participant blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Post-ERCP Pancreatitis	The incidence of post-ERCP pancreatitis (PEP) following biliary ERCP, defined using standard consensus criteria: new or worsened abdominal pain consistent with acute pancreatitis, elevation of serum amylase or lipase to at least three times the upper limit of normal within 24 hours after ERCP, and hospitalization or prolongation of planned admission attributable to pancreatitis. The outcome will be compared between participants receiving prophylactic rectal indomethacin and those receiving placebo.	Within 30 days following ERCP Procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Post-ERCP Pancreatitis	Severity of post-ERCP pancreatitis classified according to standard consensus criteria as mild, moderate, or severe among participants who develop post-ERCP pancreatitis.	Within 30 days of ERCP
Incidence of ERCP-Related Adverse Events	Incidence of ERCP-related complications, including bleeding, infection, and perforation, occurring after the ERCP procedure.	Within 30 days of ERCP Procedure
Incidence of Indomethacin-Related Adverse Events	Incidence of adverse events potentially attributable to indomethacin administration, including gastrointestinal bleeding, renal dysfunction, and allergic or hypersensitivity reactions.	Within 30 days of ERCP Procedure
Hospital Admission Following ERCP	Proportion of participants requiring hospitalization or unplanned admission following ERCP due to post-procedure complications.	Within 30 of ERCP Procedure

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Michael Larsen, MD, University of California, San Francisco

Publications and helpful links

General Publications

• Elmunzer BJ, Scheiman JM, Lehman GA, Chak A, Mosler P, Higgins PD, Hayward RA, Romagnuolo J, Elta GH, Sherman S, Waljee AK, Repaka A, Atkinson MR, Cote GA, Kwon RS, McHenry L, Piraka CR, Wamsteker EJ, Watkins JL, Korsnes SJ, Schmidt SE, Turner SM, Nicholson S, Fogel EL; U.S. Cooperative for Outcomes Research in Endoscopy (USCORE). A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012 Apr 12;366(15):1414-22. doi: 10.1056/NEJMoa1111103.
• 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.
• ASGE Standards of Practice Committee; Buxbaum JL, Abbas Fehmi SM, Sultan S, Fishman DS, Qumseya BJ, Cortessis VK, Schilperoort H, Kysh L, Matsuoka L, Yachimski P, Agrawal D, Gurudu SR, Jamil LH, Jue TL, Khashab MA, Law JK, Lee JK, Naveed M, Sawhney MS, Thosani N, Yang J, Wani SB. ASGE guideline on the role of endoscopy in the evaluation and management of choledocholithiasis. Gastrointest Endosc. 2019 Jun;89(6):1075-1105.e15. doi: 10.1016/j.gie.2018.10.001. Epub 2019 Apr 9.
• Sawaf B, Najah Q, Almoshantaf MB, Alom M, Hallak YO, Albuni MK, Elhadi M, Alastal Y. Rectal Indomethacin in Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: An Updated Meta-Analysis with Trial Sequential Analysis. Dig Dis. 2025;43(6):706-717. doi: 10.1159/000548343. Epub 2025 Sep 5.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2031
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: June 11, 2026
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: ERCP; pancreatitis; post-ERCP pancreatitis; PEP; pancreatitis acute biliary; post-ERCP adverse events
• 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: 25-44446

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes