Papillary Epinephrine Injection vs Rectal Indomethacin

NCT07173179 | Completed Phase 4

• 1 other identifier: Rectal NSAID vs Epi injection
• Study Type: interventional
• Target: 504
• Locations: 1 country
• Sites: 1

Brief Summary

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common and one of the most undesirable major adverse events after endoscopic retrograde cholangiopancreatography (ERCP), causing significant morbidity and even mortality. The incidence rate is almost 15% in high-risk patients and no less than 3% in average-risk patients. Many factors contribute to PEP, such as patient-related and endoscopist-related factors, but mainly two mechanisms are considered in terms of physiopathology: papillary edema caused by mechanical trauma during cannulation and thermal injury with electrocautery current. Rectal NSAIDs and pancreatic stent placement are the two proven methods of PEP prophylaxis included in the guideline recommendations, but despite their frequent use, the incidence rates remain unacceptably high. There is a need for additional methods that are easy to implement, preferably low-cost, and safe to reduce the risk of PEP. Topical epinephrine applied submucosally can meet these goals. Ampullary epinephrine injection is an effective method for post-sphincterotomy bleeding. Still, to our knowledge, no study has examined its efficacy in PEP prophylaxis, except for the retrospective study we reported. There are conflicting reports on epinephrine spraying onto the papilla for PEP, but these trials are largely heterogeneous, with different dose regimens. It should also be noted that spraying epinephrine onto the papilla has a duration of action of about 1 to 5 minutes, whereas epinephrine injection has a duration of roughly 120 minutes. Given this information, a large-scale, prospective, double-blind, randomized, controlled trial is designed.

Conditions

Post-ERCP Acute Pancreatitis

Keywords

ERCP; post-ercp acute pancreatitis; epinephrine; indomethacin

Outcome Measures

Primary Outcomes (1)

• Overall post-ERCP pancreatitis rate

  The rate of post-ERCP pancreatitis

  30 days

Secondary Outcomes (4)

• Overall post-ERCP pancreatitis rate in high risk patients

  30 days

• Post sphincterotomy bleeding

  30 days

• Overall ERCP complications

  30 days

• Length of hospital stay

  30 days

Study Arms (2)

Rectal indomethacin

ACTIVE COMPARATOR

The patients will receive 100mg of rectal indomethacin alone, just before the procedure

Drug: Indomethacin

Peripapillary epinephrine injection

EXPERIMENTAL

The patients will receive a peripapillary injection of 4mg undiluted epinephrine, divided into 1mg in each quadrant of the peripapillary region, 1 to 2 cm from the papillary orifice, in 60 seconds, at the end of the procedure

Procedure: Epinephrine injection

Interventions

Indomethacin DRUG

The patients in Group A will receive 100mg of rectal indomethacin alone, just before the procedure

Rectal indomethacin

Epinephrine injection PROCEDURE

The patients will receive a peripapillary injection of 4mg undiluted epinephrine, divided into 1mg in each quadrant of the peripapillary region, 1 to 2 cm from the papillary orifice, at the end of the procedure, in 60 seconds

Peripapillary epinephrine injection

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Pregnancy
• Inability to provide written informed consent
• Previous history of ERCP
• Ampulla of Vater cancer
• Surgically altered anatomy

Sponsors & Collaborators

• Duzce University: lead

Study Sites (1)

Duzce University School of Medicine

Düzce, 81620, Turkey (Türkiye)

Location

Related Publications (9)

• Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR, Spirito F, Pilotto A, Forlano R. Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol. 2007 Aug;102(8):1781-8. doi: 10.1111/j.1572-0241.2007.01279.x. Epub 2007 May 17.

  PMID: 17509029 BACKGROUND

• Kochar B, Akshintala VS, Afghani E, Elmunzer BJ, Kim KJ, Lennon AM, Khashab MA, Kalloo AN, Singh VK. Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials. Gastrointest Endosc. 2015 Jan;81(1):143-149.e9. doi: 10.1016/j.gie.2014.06.045. Epub 2014 Aug 1.

  PMID: 25088919 BACKGROUND

• Pezzilli R, Romboli E, Campana D, Corinaldesi R. Mechanisms involved in the onset of post-ERCP pancreatitis. JOP. 2002 Nov;3(6):162-8.

  PMID: 12432182 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

• Torun S, Odemis B, Cetin MF, Onmez A, Coskun O. Efficacy of Epinephrine Injection in Preventing Post-ERCP Pancreatitis. Surg Laparosc Endosc Percutan Tech. 2020 Oct 12;31(2):208-214. doi: 10.1097/SLE.0000000000000867.

  PMID: 33048897 BACKGROUND

• Akshintala VS, Hutfless SM, Colantuoni E, Kim KJ, Khashab MA, Li T, Elmunzer BJ, Puhan MA, Sinha A, Kamal A, Lennon AM, Okolo PI, Palakurthy MK, Kalloo AN, Singh VK. Systematic review with network meta-analysis: pharmacological prophylaxis against post-ERCP pancreatitis. Aliment Pharmacol Ther. 2013 Dec;38(11-12):1325-37. doi: 10.1111/apt.12534. Epub 2013 Oct 20.

  PMID: 24138390 BACKGROUND

• Aziz M, Ghanim M, Sheikh T, Sharma S, Ghazaleh S, Fatima R, Khan Z, Lee-Smith W, Nawras A. Rectal indomethacin with topical epinephrine versus indomethacin alone for preventing Post-ERCP pancreatitis - A systematic review and meta-analysis. Pancreatology. 2020 Apr;20(3):356-361. doi: 10.1016/j.pan.2020.02.003. Epub 2020 Feb 19.

  PMID: 32107191 BACKGROUND

• Igawa M, Miyaoka M, Saitoh T. Influence of topical epinephrine application on microcirculatory disturbance in subjects with ulcerative colitis evaluated by laser Doppler flowmetry and transmission electron microscopy. Dig Endosc. 2000;12:126-130

  BACKGROUND

• Chung SC, Leung JW, Leung FW. Effect of submucosal epinephrine injection on local gastric blood flow. A study using laser Doppler flowmetry and reflectance spectrophotometry. Dig Dis Sci. 1990 Aug;35(8):1008-11. doi: 10.1007/BF01537250.

  PMID: 2384031 BACKGROUND

MeSH Terms

Interventions

Epinephrine; Indomethacin

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Salih Tokmak

  Duzce University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized into two groups: rectal indomethacin (Group A) and epinephrine injection (Group B), by computer-generated, numbered, sealed envelopes for treatment assignments. The envelopes will be opened at the end of the procedure, just before the intervention, to enable blinding of the endoscopists. in the randomization process The patients in Group A will receive 100mg of rectal indomethacin alone, just before the procedure. The patients in Group B will receive a peripapillary injection of 4mg undiluted epinephrine, divided into 1mg in each quadrant of the peripapillary region, 1 to 2 cm from the papillary orifice

Study Record Dates

• First Submitted: September 8, 2025
• First Posted: September 15, 2025
• Study Start: January 1, 2023
• Primary Completion: March 1, 2025
• Study Completion: May 1, 2025
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)