Papillary Epinephrine Injection Combined With Rectal Indomethacin

NCT07173179 | Completed Phase 4

• 1 other identifier: Rectal NSAID vs EI combo
• 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 that are included in the guideline recommendations, but despite the frequent use of these methods, the incidence rates are still more than acceptable. 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 be a method that meets these goals. Ampullary epinephrine injection is an effective method in terms of post sphincterotomy bleeding but to our knowledge, there is no study examining its efficacy in PEP prophylaxis except for one retrospective study that we reported. There are conflicting reports on epinephrine spraying on the papilla in terms of PEP, but these trials are mostly heterogeneous with different dose regimens. It should also be noted that spraying epinephrine on the papilla has a length of action of about 1 to 5 minutes but the length of action for epinephrine injection is roughly 120 minutes. Given this information, we designed a large-scale, double-blind, randomized, controlled, superiority trial.

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 (5)

• Overall post-ERCP pancreatitis rate in high risk patients

  30 days

• Overall post-ERCP hyperamylasemia

  30 days

• Post sphincterotomy bleeding

  30 days

• Overall ERCP complications

  30 days

• Length of hospital stay

  30 days

Study Arms (2)

Rectal indomethacin alone

ACTIVE COMPARATOR

All patients in this group receive preprocedural 100mg indomethacin spp

Drug: Rectal indomethacin alone

Rectal indomethacin combined wit papillary epinephrine injection

EXPERIMENTAL

All patients in this group receive preprocedural 100mg indomethacin spp and post-procedure 4 ml of undiluted epinephrine injected around the duodenal papilla on four quadrants, over a period of 60 seconds using a sclerotherapy needle

Drug: Papillary epinephrine injection combined with rectal indomethacin

Interventions

Papillary epinephrine injection combined with rectal indomethacin DRUG

All patients in this group receive preprocedural 100mg indomethacin spp and post-procedure 4 ml of undiluted epinephrine injected around the duodenal papilla on four quadrants, over a period of 60 seconds using a sclerotherapy needle

Also known as: PEI

Rectal indomethacin combined wit papillary epinephrine injection

Rectal indomethacin alone DRUG

All patients in this group receive preprocedural 100mg indomethacin spp

Also known as: RI

Rectal indomethacin alone

Eligibility Criteria

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

You may qualify if:

• Patients who submitted a written informed consent for this trial, and aged between 18-80 years old
• Patients who have naïve papilla (no previous procedure was performed at ampulla)
• Patients who is suspected to have a biliary obstruction or biliary disease
• Patients who are needed to have endoscopic retrograde cholangiopancreatography for treatment of biliary obstruction

You may not qualify if:

• Patients who are pregnant
• Patients with mental retardation
• Patients allergic to contrast agents
• Patients who received sphincterotomy or pancreatobiliary operation previously
• Patients who have ampulla of Vater cancer
• Patients who have difficulty with the approach to ampulla due to abdominal surgery including stomach cancer with Billroth II anastomosis
• Patients who have pancreatic diseases as below (at least one more);
• acute pancreatitis within 30days before enrollment
• idiopathic acute recurrent pancreatitis
• pancreas divisum
• obstructive chronic pancreatitis
• pancreatic cancer

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

Study Officials

• Salih Tokmak

  Duzce University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 8, 2025
• First Posted: September 15, 2025
• Study Start: July 1, 2022
• Primary Completion: February 1, 2023
• Study Completion: April 1, 2023
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)