Rectal Indomethacin and Oral Tacrolimus Versus Combination to Prevent Post-ERCP Pancreatitis

NCT05252754 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: IRB00269963
• Study Type: interventional
• Target: 4,874
• Locations: 3 countries
• Sites: 5

Brief Summary

This research is being done to see if using oral tacrolimus before endoscopy, can prevent pancreatitis that may occur after ERCP (a type of gastrointestinal endoscopy).

Conditions

Post-ERCP Acute Pancreatitis

Outcome Measures

Primary Outcomes (1)

• The proportion of subjects in each study group with Post ERCP Acute Pancreatitis (PEP)

  Incidence of PEP as defined by the consensus guidelines as 1. New or increased abdominal pain that is clinically consistent with a syndrome of acute pancreatitis 2. Amylase or lipase ≥ 3x the upper limit of normal 24 hours after the procedure 3. Hospitalization or prolongation of existing hospitalization for at least 2 days

  Within 30 days of ERCP

Secondary Outcomes (1)

• The proportion of subjects in each study group with moderate-severe Post-ERCP Pancreatitis

  Within 30 days of ERCP

Study Arms (2)

Oral Tacrolimus + Indomethacin

EXPERIMENTAL

* Tacrolimus Capsule 1-2 hours prior to the endoscopy * Rectal Indomethacin immediately after ERCP, in high-risk patients

Drug: Tacrolimus capsule; Drug: Rectal Indomethacin

Oral Placebo + Indomethacin

PLACEBO COMPARATOR

* Placebo Capsule 1-2 hours prior to the endoscopy * Rectal Indomethacin immediately after ERCP, in high-risk patients

Drug: Placebo; Drug: Rectal Indomethacin

Interventions

Tacrolimus capsule DRUG

Tacrolimus 5 mg PO, 1-2 hours prior to endoscopy

Also known as: Prograf, Protopic

Oral Tacrolimus + Indomethacin

Placebo DRUG

Placebo PO, 1-2 hours prior to endoscopy.

Oral Placebo + Indomethacin

Rectal Indomethacin DRUG

100 mg Rectal Indomethacin immediately after ERCP, in high-risk patients.

Also known as: Indocin, NSAIDS

Oral Placebo + Indomethacin; Oral Tacrolimus + Indomethacin

Eligibility Criteria

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

You may qualify if:

• Any patient who is undergoing endoscopic retrograde cholangiopancreatography (ERCP) at any of the participating centers, is at least 18 years old and provides informed consent can be included in the study.

You may not qualify if:

• Unwillingness or inability to consent for the study.
• Pregnancy
• Breastfeeding mother
• Chronic calcific pancreatitis
• ERCP for biliary stent exchange or removal
• ERCP in a patient with prior biliary sphincterotomy, but without anticipated pancreatogram.
• Biliary intervention in a patient with pancreas divisum.
• Standard contraindications to tacrolimus or NSAID use.
• Current tacrolimus or immune modulator use.
• Chronic kidney disease with glomerular filtration rate (GFR) \< 30 or acute kidney injury.
• Absence of rectum.
• Acute pancreatitis within 30 days of ERCP.
• Pancreatic head malignancy.
• Sphincter of Oddi dysfunction (Type 3).

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (5)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

Asian Institute of Gastroenterology

Hyderabad, Andhra Pradesh, 500082, India

RECRUITING

Apollo Multispecialty Hospitals,

Kolkata, West Bengal, 700054, India

NOT YET RECRUITING

Post Graduate Institute of Medical Education and Research

Chandigarh, 160012, India

NOT YET RECRUITING

Singapore General Hospital

Singapore, 169608, Singapore

NOT YET RECRUITING

Related Publications (16)

• Coelho-Prabhu N, Shah ND, Van Houten H, Kamath PS, Baron TH. Endoscopic retrograde cholangiopancreatography: utilisation and outcomes in a 10-year population-based cohort. BMJ Open. 2013 May 31;3(5):e002689. doi: 10.1136/bmjopen-2013-002689.

  PMID: 23793659 BACKGROUND

• Mazen Jamal M, Yoon EJ, Saadi A, Sy TY, Hashemzadeh M. Trends in the utilization of endoscopic retrograde cholangiopancreatography (ERCP) in the United States. Am J Gastroenterol. 2007 May;102(5):966-75. doi: 10.1111/j.1572-0241.2007.01127.x. Epub 2007 Mar 23.

  PMID: 17319932 BACKGROUND

• Moffatt DC, Yu BN, Yie W, Bernstein CN. Trends in utilization of diagnostic and therapeutic ERCP and cholecystectomy over the past 25 years: a population-based study. Gastrointest Endosc. 2014 Apr;79(4):615-22. doi: 10.1016/j.gie.2013.08.028. Epub 2013 Oct 8.

  PMID: 24119510 BACKGROUND

• Testoni PA, Mariani A, Giussani A, Vailati C, Masci E, Macarri G, Ghezzo L, Familiari L, Giardullo N, Mutignani M, Lombardi G, Talamini G, Spadaccini A, Briglia R, Piazzi L; SEIFRED Group. Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study. Am J Gastroenterol. 2010 Aug;105(8):1753-61. doi: 10.1038/ajg.2010.136. Epub 2010 Apr 6.

  PMID: 20372116 BACKGROUND

• Fan JH, Qian JB, Wang YM, Shi RH, Zhao CJ. Updated meta-analysis of pancreatic stent placement in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis. World J Gastroenterol. 2015 Jun 28;21(24):7577-83. doi: 10.3748/wjg.v21.i24.7577.

  PMID: 26140006 BACKGROUND

• Lyu Y, Cheng Y, Wang B, Xu Y, Du W. What is impact of nonsteroidal anti-inflammatory drugs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized controlled trials. BMC Gastroenterol. 2018 Jul 4;18(1):106. doi: 10.1186/s12876-018-0837-4.

  PMID: 29973142 BACKGROUND

• Levenick JM, Gordon SR, Fadden LL, Levy LC, Rockacy MJ, Hyder SM, Lacy BE, Bensen SP, Parr DD, Gardner TB. Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients. Gastroenterology. 2016 Apr;150(4):911-7; quiz e19. doi: 10.1053/j.gastro.2015.12.040. Epub 2016 Jan 9.

  PMID: 26775631 BACKGROUND

• Shibasaki F, Hallin U, Uchino H. Calcineurin as a multifunctional regulator. J Biochem. 2002 Jan;131(1):1-15. doi: 10.1093/oxfordjournals.jbchem.a003063.

  PMID: 11754729 BACKGROUND

• Rusnak F, Mertz P. Calcineurin: form and function. Physiol Rev. 2000 Oct;80(4):1483-521. doi: 10.1152/physrev.2000.80.4.1483.

  PMID: 11015619 BACKGROUND

• Aramburu J, Rao A, Klee CB. Calcineurin: from structure to function. Curr Top Cell Regul. 2000;36:237-95. doi: 10.1016/s0070-2137(01)80011-x. No abstract available.

  PMID: 10842755 BACKGROUND

• Muili KA, Ahmad M, Orabi AI, Mahmood SM, Shah AU, Molkentin JD, Husain SZ. Pharmacological and genetic inhibition of calcineurin protects against carbachol-induced pathological zymogen activation and acinar cell injury. Am J Physiol Gastrointest Liver Physiol. 2012 Apr 15;302(8):G898-905. doi: 10.1152/ajpgi.00545.2011. Epub 2012 Feb 9.

  PMID: 22323127 BACKGROUND

• Thiruvengadam NR, Forde KA, Chandrasekhara V, Ahmad NA, Ginsberg GG, Khungar V, Kochman ML. Tacrolimus and Indomethacin Are Safe and Effective at Reducing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography in Patients Who Have Undergone Liver Transplantation. Clin Gastroenterol Hepatol. 2020 May;18(5):1224-1232.e1. doi: 10.1016/j.cgh.2019.10.014. Epub 2019 Oct 14.

  PMID: 31622734 BACKGROUND

• Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, Warty V, McMichael J, Lever J, Burckart G, Starzl T. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet. 1995 Dec;29(6):404-30. doi: 10.2165/00003088-199529060-00003.

  PMID: 8787947 BACKGROUND

• Wen L, Javed TA, Yimlamai D, Mukherjee A, Xiao X, Husain SZ. Transient High Pressure in Pancreatic Ducts Promotes Inflammation and Alters Tight Junctions via Calcineurin Signaling in Mice. Gastroenterology. 2018 Oct;155(4):1250-1263.e5. doi: 10.1053/j.gastro.2018.06.036. Epub 2018 Jun 19.

  PMID: 29928898 BACKGROUND

• Orabi AI, Wen L, Javed TA, Le T, Guo P, Sanker S, Ricks D, Boggs K, Eisses JF, Castro C, Xiao X, Prasadan K, Esni F, Gittes GK, Husain SZ. Targeted inhibition of pancreatic acinar cell calcineurin is a novel strategy to prevent post-ERCP pancreatitis. Cell Mol Gastroenterol Hepatol. 2017 Jan;3(1):119-128. doi: 10.1016/j.jcmgh.2016.08.006.

  PMID: 28090570 BACKGROUND

• Akshintala VS, Husain SZ, Brenner TA, Singh A, Singh VK, Khashab MA, Sperna Weiland CJ, van Geenen EJM, Bush N, Barakat M, Srivastava A, Kochhar R, Talukdar R, Rodge G, Wu CCH, Lakhtakia S, Sinha SK, Goenka MK, Reddy DN. Rectal INdomethacin, oral TacROlimus, or their combination for the prevention of post-ERCP pancreatitis (INTRO Trial): Protocol for a randomized, controlled, double-blinded trial. Pancreatology. 2022 Nov;22(7):887-893. doi: 10.1016/j.pan.2022.07.008. Epub 2022 Jul 19.

  PMID: 35872074 DERIVED

MeSH Terms

Interventions

Tacrolimus; Indomethacin; Anti-Inflammatory Agents, Non-Steroidal

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents

Study Officials

• Venkata S. Akshintala, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Venkata S. Akshintala, M.D.

CONTACT

+1 (410) 614-6708; vakshin1@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: February 23, 2022
• Study Start: January 18, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

IN (3); SG (1); US (1)