NCT07083063

Brief Summary

Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure combining endoscopy and fluoroscopy to diagnose and treat pancreaticobiliary disorders such as bile duct stones, strictures, and cholangitis. Despite its therapeutic value, ERCP carries a relatively high complication risk of about 10%, with severe complications occurring in roughly 24% of those affected and mortality rates between 0.2% and 0.7%. The most common and significant complication is post-ERCP pancreatitis (PEP), occurring in 2% to 10% of average patients and up to 40% or higher in high-risk groups. PEP ranges from mild, self-limiting inflammation to severe, life-threatening conditions including pancreatic necrosis and multi-organ failure. PEP arises from mechanical trauma, hydrostatic injury, chemical irritation, or infection during ERCP that activates inflammatory pathways within the pancreas. Key patient-related risk factors include young age, female sex, prior pancreatitis, and sphincter of Oddi dysfunction; procedural factors include difficult biliary cannulation, pancreatic duct manipulation, and precut sphincterotomy. Preventive strategies focus on minimizing mechanical injury and pharmacologic prophylaxis. Rectal NSAIDs (indomethacin, diclofenac) administered immediately before ERCP are well-supported for reducing PEP risk. Periprocedural aggressive intravenous hydration and prophylactic pancreatic duct stenting in high-risk cases also lower PEP incidence. Nitroglycerin, a smooth muscle relaxant acting via nitric oxide-mediated sphincter relaxation, has shown promise in PEP prevention, especially in patients contraindicated for NSAIDs. Clinical trials indicate that transdermal or sublingual nitroglycerin reduces PEP rates, and combined use with NSAIDs may enhance protection. However, current guidelines do not routinely recommend nitroglycerin due to limited consensus on its efficacy. Topical nitroglycerin, known to relax smooth muscles locally and used in anorectal conditions, might reduce sphincter of Oddi pressure without systemic side effects. This suggests potential benefit in lowering PEP incidence or severity when applied topically during ERCP, pending further investigation. This study aimed to investigate whether topical delivery of nitroglycerin can reduce the incidence rate of PEP or the severity of pancreatitis.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
440

participants targeted

Target at P75+ for phase_4

Timeline
15mo left

Started Sep 2025

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress34%
Sep 2025Jul 2027

First Submitted

Initial submission to the registry

July 16, 2025

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 24, 2025

Completed
2 months until next milestone

Study Start

First participant enrolled

September 15, 2025

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2027

Last Updated

December 8, 2025

Status Verified

July 1, 2025

Enrollment Period

1.9 years

First QC Date

July 16, 2025

Last Update Submit

December 1, 2025

Conditions

Pancreatitis

Keywords

post-ERCP pancreatitisnitroglycerin

Outcome Measures

Primary Outcomes (1)

  • Occurrence of Post-ERCP pancreatitis

    Incidence of Post-ERCP pancreatitis based on a widely recognised Cotton consensus, which is defined as a three-fold increase of serum lipase at ≥24 h and necessitating hospital admission or prolonged hospital stay.

    7 days

Secondary Outcomes (5)

  • Occurence of moderate or severe PEP

    7 days

  • Occurrence of post-ERCP bleeding

    14 days

  • Occurrence of shock status

    1 day

  • Length of hospitalization

    14 days

  • Level of pancreatic serology

    8 hours

Study Arms (2)

Intervention Group

EXPERIMENTAL

diluted 1mg nitroglycerin in normal saline (1mg/10cc) will be delivered to the major papilla in the intervention group.

Drug: Nitroglycerin (NTG)

Standard Group

PLACEBO COMPARATOR

10cc normal saline will be delivered to the major papilla in the standard group.

Drug: Normal Saline (0.9% NaCl)

Interventions

Normal Saline (0.9% NaCl)DRUG

All patients without chronic kidney disease (serum creatine \> 1.5 mg/dL) will receive rectal diclofenac 100 mg before the procedure. During the biliary cannulation, if twice or more times of pancreatic duct cannulation, a pancreatic plastic stent will be placed. Lactate ringer hydration will be provided to patients with pancreatic duct cannulation for 24 hours. After the EST and stone extraction, we will randomly assign the patients to either a control or an intervention group. After EST, if immediate bleeding occurs, we will apply standard endoscopic therapy by either local injection of diluted epinephrine or heater probe coagulation. Before the end of the exam, diluted 1mg nitroglycerin in normal saline (1mg/10cc) will be delivered to the major papilla in the intervention group.

Standard Group
Nitroglycerin (NTG)DRUG

All patients without chronic kidney disease (serum creatine \> 1.5 mg/dL) will receive rectal diclofenac 100 mg before the procedure. During the biliary cannulation, if twice or more times of pancreatic duct cannulation, a pancreatic plastic stent will be placed. Lactate ringer hydration will be provided to patients with pancreatic duct cannulation for 24 hours. After the EST and stone extraction, we will randomly assign the patients to either a control or an intervention group. After EST, if immediate bleeding occurs, we will apply standard endoscopic therapy by either local injection of diluted epinephrine or heater probe coagulation. Before the end of the exam, diluted 1mg nitroglycerin in normal saline (1mg/10cc) will be delivered to the major papilla in the intervention group, and 10cc normal saline will be delivered to the major papilla in the standard group.

Intervention Group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Eligible participants include patients aged ≥ 18 years who accept ERCP and sphincterotomy for common bile duct (CBD) stone extraction.

You may not qualify if:

  • patients with pancreatic cancer
  • shock status (systolic blood pressure \< 90 mmHg or using inotropic agents)
  • allergy to NTG
  • angle-closure glaucoma
  • severe anemia
  • patients on PDE 5 inhibitors

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Cheng Kung University Hospital

Tainan, Other (Non U.s.), 704, Taiwan

RECRUITING

Related Publications (15)

  • Jin J, Unasa H, Bahl P, Mauiliu-Wallis M, Svirskis D, Hill A. Can Targeting Sphincter Spasm Reduce Post-Haemorrhoidectomy Pain? A Systematic Review and Meta-Analysis. World J Surg. 2023 Feb;47(2):520-533. doi: 10.1007/s00268-022-06807-3. Epub 2022 Nov 10.

    PMID: 36357803RESULT

  • Hussain S, Ammar AS, Hameed AR, Aslam I, Afzal A. Comparison of outcome of botulinum toxin injection with and without glyceryl trinitrate in chronic anal fissure in terms of post operative pain and healing. J Pak Med Assoc. 2024 Jul;74(7):1245-1248. doi: 10.47391/JPMA.9726.

    PMID: 39028048RESULT

  • Khan SS, Martin S, Doh CY, Stein SL, Steinhagen E. Trends in Management of Anal Fissures. Am Surg. 2024 Mar;90(3):393-398. doi: 10.1177/00031348231200662. Epub 2023 Sep 2.

    PMID: 37658717RESULT

  • Canlikarakaya F, Ocakli S. Can Topical Glyceryl Trinitrate be Effective in the Treatment of Levator Ani Syndrome? Turk J Gastroenterol. 2025 Jan 13;36(5):328-327. doi: 10.5152/tjg.2025.24489.

    PMID: 39840843RESULT

  • Kubiliun NM, Adams MA, Akshintala VS, Conte ML, Cote GA, Cotton PB, Dumonceau JM, Elta GH, Fogel EL, Freeman ML, Lehman GA, Naveed M, Romagnuolo J, Scheiman JM, Sherman S, Singh VK, Elmunzer BJ; United States Cooperative for Outcomes Research in Endoscopy (USCORE). Evaluation of Pharmacologic Prevention of Pancreatitis After Endoscopic Retrograde Cholangiopancreatography: A Systematic Review. Clin Gastroenterol Hepatol. 2015 Jul;13(7):1231-9; quiz e70-1. doi: 10.1016/j.cgh.2014.11.038. Epub 2015 Jan 9.

    PMID: 25579870RESULT

  • Bai Y, Xu C, Yang X, Gao J, Zou DW, Li ZS. Glyceryl trinitrate for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography: a meta-analysis of randomized, double-blind, placebo-controlled trials. Endoscopy. 2009 Aug;41(8):690-5. doi: 10.1055/s-0029-1214951. Epub 2009 Aug 10.

    PMID: 19670137RESULT

  • Wang Y, Xu B, Zhang W, Lin J, Li G, Qiu W, Wang Y, Sun D, Wang Y. Prophylactic effect of rectal indomethacin plus nitroglycerin administration for preventing pancreatitis after endoscopic retrograde cholangiopancreatography in female patients. Ann Palliat Med. 2020 Nov;9(6):4029-4037. doi: 10.21037/apm-20-1963.

    PMID: 33302662RESULT

  • Hao JY, Wu DF, Wang YZ, Gao YX, Lang HP, Zhou WZ. Prophylactic effect of glyceryl trinitrate on post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized placebo-controlled trial. World J Gastroenterol. 2009 Jan 21;15(3):366-8. doi: 10.3748/wjg.15.366.

    PMID: 19140238RESULT

  • Nojgaard C, Hornum M, Elkjaer M, Hjalmarsson C, Heyries L, Hauge T, Bakkevold K, Andersen PK, Matzen P; European Post-ERCP Pancreatitis Preventing Study Group. Does glyceryl nitrate prevent post-ERCP pancreatitis? A prospective, randomized, double-blind, placebo-controlled multicenter trial. Gastrointest Endosc. 2009 May;69(6):e31-7. doi: 10.1016/j.gie.2008.11.042.

    PMID: 19410035RESULT

  • Kaffes AJ, Bourke MJ, Ding S, Alrubaie A, Kwan V, Williams SJ. A prospective, randomized, placebo-controlled trial of transdermal glyceryl trinitrate in ERCP: effects on technical success and post-ERCP pancreatitis. Gastrointest Endosc. 2006 Sep;64(3):351-7. doi: 10.1016/j.gie.2005.11.060. Epub 2006 May 19.

    PMID: 16923481RESULT

  • Moreto M, Zaballa M, Casado I, Merino O, Rueda M, Ramirez K, Urcelay R, Baranda A. Transdermal glyceryl trinitrate for prevention of post-ERCP pancreatitis: A randomized double-blind trial. Gastrointest Endosc. 2003 Jan;57(1):1-7. doi: 10.1067/mge.2003.29.

    PMID: 12518122RESULT

  • 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: 25088919RESULT

  • Kwak N, Yeoun D, Arroyo-Mercado F, Mubarak G, Cheung D, Vignesh S. Outcomes and risk factors for ERCP-related complications in a predominantly black urban population. BMJ Open Gastroenterol. 2020 Sep;7(1):e000462. doi: 10.1136/bmjgast-2020-000462.

    PMID: 32943462RESULT

  • Fujita K, Yazumi S, Matsumoto H, Asada M, Nebiki H, Matsumoto K, Maruo T, Takenaka M, Tomoda T, Onoyama T, Kurita A, Ueki T, Katayama T, Kawamura T, Kawamoto H; Bilio-pancreatic Study Group of West Japan. Multicenter prospective cohort study of adverse events associated with biliary endoscopic retrograde cholangiopancreatography: Incidence of adverse events and preventive measures for post-endoscopic retrograde cholangiopancreatography pancreatitis. Dig Endosc. 2022 Sep;34(6):1198-1204. doi: 10.1111/den.14225. Epub 2022 Feb 4.

    PMID: 34963021RESULT

  • 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.

    PMID: 30979521RESULT

MeSH Terms

Conditions

Pancreatitis

Interventions

NitroglycerinSaline Solution

Condition Hierarchy (Ancestors)

Pancreatic DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

Nitro CompoundsOrganic ChemicalsCrystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Central Study Contacts

Hsueh-Chien Chiang, MD

CONTACT

+88662353535scion456scion@gmail.com

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: All patients without chronic kidney disease (serum creatine \> 1.5 mg/dL) will receive rectal diclofenac 100 mg before the procedure. During the biliary cannulation, if twice or more times of pancreatic duct cannulation, a pancreatic plastic stent will be placed. Lactate ringer hydration with standard dose (1.5 kg/cc/hr) will be provided to patients with pancreatic duct cannulation for 8 hours. After the EST and stone extraction, we will randomly assign the patients to either a control or an intervention group. After EST, if immediate bleeding occurs, investigators will apply standard endoscopic therapy by either local injection of diluted epinephrine or heater probe coagulation. Before the end of the exam, diluted 1mg nitroglycerin in normal saline (1mg/10cc) will be delivered to the major papilla in the intervention group. Normal saline 10cc will be delivered to the major papilla in the standard group.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Doctor

Study Record Dates

First Submitted

July 16, 2025

First Posted

July 24, 2025

Study Start

September 15, 2025

Primary Completion (Estimated)

July 31, 2027

Study Completion (Estimated)

July 31, 2027

Last Updated

December 8, 2025

Record last verified: 2025-07

Data Sharing

IPD Sharing
Will share
Shared Documents
STUDY PROTOCOL

Locations

TW(1)