Comparative Effectiveness Between Indomethacin and Pancreatic Stenting in the Prevention of Post ERCP Pancreatitis

NCT03713879 | Recruiting Phase 3 DMC

• 1 other identifier: StentvsNSAID
• Study Type: interventional
• Target: 1,734
• Locations: 3 countries
• Sites: 7

Brief Summary

Post ERCP pancreatitis (PEP) occurs in 4 to 5% of patients and is associated with significant morbidities and occasional mortalities. The use of rectall administered indomethacin and pancreatic duct stent (PDS) placement have independently been proven to reduce PEP. The comparative effectiveness of the two methods has however not been studied. It is argued that in the context of indomethacin, the placement of a PDS is unnecessary. Advocates for PDS insertion however believe that mechanical decompression of the pancreatic duct is critical in the prevention of pancreatitis. The investigators propose a multi-centre randomised controlled trial to compare the use of rectal indomethacin to PDS insertion in high risk patients in the prevention of PEP.

Conditions

Post ERCP Pancreatitis

Keywords

post ERCP panceatitis; rectal indomethacin; pancreatic stents

Outcome Measures

Primary Outcomes (3)

• post-ERCP pancreatitis

  Percentage of Participants with post ERCP pancreatitis

  30 days

• high severity of post-ERCP pancreatitis

  Percentage of Participants with high severity of post-ERCP pancreatitis using the Clavian-Dindo classification (1 / 2 / 3 / 3a / 3b / 4 / 4a/ 4b / 5)

  30 days

• pancreatitis with complications

  Percentage of Participants with pancreatitis with complications using Atlanta classification (Mild / Moderate / Severe / Critical )

  30 days

Secondary Outcomes (4)

• hospital stay

  30 days

• endoscopic intervention due to PEP

  30 days

• radiologic intervention due to PEP

  30 days

• surgery due to PEP

  30 days

Study Arms (3)

indomethacin

EXPERIMENTAL

rectal indomethacin 100 mg to be administered before or after ERCP

Drug: Indomethacin

pancreatic stenting

EXPERIMENTAL

a PD stent to be inserted during ERCP (a 3 to 5 cm 5Fr single pigtail pancreatic duct stent without inner flap is used, the stent is inserted after deep cannulation of pancreatic duct with a .025" or .035" wire)

Device: pancreatic stenting

indomethacin plus pancreatic stenting

EXPERIMENTAL

\[rectal indomethacin 100 mg to be administered before or after ERCP\] plus \[a PD stent to be inserted during ERCP (a 3 to 5 cm 5Fr single pigtail pancreatic duct stent without inner flap is used, the stent is inserted after deep cannulation of pancreatic duct with a .025" or .035" wire\]

Device: pancreatic stenting; Drug: Indomethacin

Interventions

pancreatic stenting DEVICE

a PD stent to be inserted during ERCP (a 3 to 5 cm 5Fr single pigtail pancreatic duct stent without inner flap is used, the stent is inserted after deep cannulation of pancreatic duct with a .025" or .035" wire)

indomethacin plus pancreatic stenting; pancreatic stenting

Indomethacin DRUG

rectally administered indomethacin before or after ERCP

Also known as: indocid

indomethacin; indomethacin plus pancreatic stenting

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• presence of one of the following risk factors for Post ERCP Pancreatitis
• sphincter of Oddi dysfunction
• history of PEP, pancreatic instrumentation or sphincterotomy, precut sphincterotomy,
• difficult cannulation defined by \>5 cannulation attempts
• the use of double wire technique in bile duct access
• at least 2 of the followings including i) female age\<50 ii) 3 pancreatograms iii) acinarization (contrast injection to tail fo pancreas). iv） normal bilirubin； v）guidewire to the tail of pancreas or secondary branches.

You may not qualify if:

• patients intended for pancreatic stenting e.g. those with pancreatic duct strictures, ampullectomy,
• without informed consents from patient or next of kin
• age \<18
• pregnant or lactating women
• patients with altered anatomy except except Billroth I and II gastrectomy
• contraindications to the use of NSAIDs such as those with active gastrointestinal bleeding, renal failure (serum creatinine \> 140)
• known NSAID allergy
• incipient heart failure.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead
• Xijing Hospital: collaborator
• Changhai Hospital: collaborator
• Tianjin Union Medical Center: collaborator
• Zhejiang University: collaborator
• Eastern Hepatobiliary Surgery Hospital: collaborator

Study Sites (7)

Endoscopy centre

Xi'an, Shaanxi, 710000, China

RECRUITING

Eastern Hepatobiliary Surgery Hospital,Endoscopy centre

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Endoscopy centre

Shanghai, Shanghai Municipality, 200000, China

NOT YET RECRUITING

Endoscopy centre

Tianjin, Tianjin Municipality, 300000, China

RECRUITING

Endoscopy centre

Hangzhou, Zhejiang, 310013, China

RECRUITING

Endoscopy Centre, Prince of Wales Hospital

Hong Kong, Hong Kong, Hong Kong

RECRUITING

2. Chulalongkorn University and King Chulalongkorn Memorial Hospital

Bangkok, Thailand

RECRUITING

Related Publications (14)

• 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

• Choudhary A, Bechtold ML, Arif M, Szary NM, Puli SR, Othman MO, Pais WP, Antillon MR, Roy PK. Pancreatic stents for prophylaxis against post-ERCP pancreatitis: a meta-analysis and systematic review. Gastrointest Endosc. 2011 Feb;73(2):275-82. doi: 10.1016/j.gie.2010.10.039.

  PMID: 21295641 BACKGROUND

• 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.

  PMID: 22494121 BACKGROUND

• Murray B, Carter R, Imrie C, Evans S, O'Suilleabhain C. Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Gastroenterology. 2003 Jun;124(7):1786-91. doi: 10.1016/s0016-5085(03)00384-6.

  PMID: 12806612 BACKGROUND

• Khoshbaten M, Khorram H, Madad L, Ehsani Ardakani MJ, Farzin H, Zali MR. Role of diclofenac in reducing post-endoscopic retrograde cholangiopancreatography pancreatitis. J Gastroenterol Hepatol. 2008 Jul;23(7 Pt 2):e11-6. doi: 10.1111/j.1440-1746.2007.05096.x. Epub 2007 Aug 7.

  PMID: 17683501 BACKGROUND

• Montano Loza A, Rodriguez Lomeli X, Garcia Correa JE, Davalos Cobian C, Cervantes Guevara G, Medrano Munoz F, Fuentes Orozco C, Gonzalez Ojeda A. [Effect of the administration of rectal indomethacin on amylase serum levels after endoscopic retrograde cholangiopancreatography, and its impact on the development of secondary pancreatitis episodes]. Rev Esp Enferm Dig. 2007 Jun;99(6):330-6. doi: 10.4321/s1130-01082007000600005. Spanish.

  PMID: 17883296 BACKGROUND

• Otsuka T, Kawazoe S, Nakashita S, Kamachi S, Oeda S, Sumida C, Akiyama T, Ario K, Fujimoto M, Tabuchi M, Noda T. Low-dose rectal diclofenac for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized controlled trial. J Gastroenterol. 2012 Aug;47(8):912-7. doi: 10.1007/s00535-012-0554-7. Epub 2012 Feb 18.

  PMID: 22350703 BACKGROUND

• Katsinelos P, Fasoulas K, Paroutoglou G, Chatzimavroudis G, Beltsis A, Terzoudis S, Katsinelos T, Dimou E, Zavos C, Kaltsa A, Kountouras J. Combination of diclofenac plus somatostatin in the prevention of post-ERCP pancreatitis: a randomized, double-blind, placebo-controlled trial. Endoscopy. 2012 Jan;44(1):53-9. doi: 10.1055/s-0031-1291440. Epub 2011 Dec 23.

  PMID: 22198776 BACKGROUND

• Sotoudehmanesh R, Khatibian M, Kolahdoozan S, Ainechi S, Malboosbaf R, Nouraie M. Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP. Am J Gastroenterol. 2007 May;102(5):978-83. doi: 10.1111/j.1572-0241.2007.01165.x. Epub 2007 Mar 13.

  PMID: 17355281 BACKGROUND

• Elmunzer BJ, Higgins PD, Saini SD, Scheiman JM, Parker RA, Chak A, Romagnuolo J, Mosler P, Hayward RA, Elta GH, Korsnes SJ, Schmidt SE, Sherman S, Lehman GA, Fogel EL; United States Cooperative for Outcomes Research in Endoscopy. Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective clinical trial data. Am J Gastroenterol. 2013 Mar;108(3):410-5. doi: 10.1038/ajg.2012.442. Epub 2013 Jan 8.

  PMID: 23295278 BACKGROUND

• Akbar A, Abu Dayyeh BK, Baron TH, Wang Z, Altayar O, Murad MH. Rectal nonsteroidal anti-inflammatory drugs are superior to pancreatic duct stents in preventing pancreatitis after endoscopic retrograde cholangiopancreatography: a network meta-analysis. Clin Gastroenterol Hepatol. 2013 Jul;11(7):778-83. doi: 10.1016/j.cgh.2012.12.043. Epub 2013 Jan 30.

  PMID: 23376320 BACKGROUND

• Choksi NS, Fogel EL, Cote GA, Romagnuolo J, Elta GH, Scheiman JM, Chak A, Mosler P, Higgins PD, Korsnes SJ, Schmidt SE, Sherman S, Lehman GA, Elmunzer BJ; United States Cooperative for Outcomes Research in Endoscopy. The risk of post-ERCP pancreatitis and the protective effect of rectal indomethacin in cases of attempted but unsuccessful prophylactic pancreatic stent placement. Gastrointest Endosc. 2015 Jan;81(1):150-5. doi: 10.1016/j.gie.2014.07.033.

  PMID: 25527053 BACKGROUND

• Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, Liguory C, Nickl N. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991 May-Jun;37(3):383-93. doi: 10.1016/s0016-5107(91)70740-2.

  PMID: 2070995 BACKGROUND

• Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibanes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009 Aug;250(2):187-96. doi: 10.1097/SLA.0b013e3181b13ca2.

  PMID: 19638912 BACKGROUND

MeSH Terms

Interventions

Indomethacin

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• James LAU, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James LAU, MD

CONTACT

35051411; laujyw@surgery.cuhk.edu.hk

RAYMOND TANG, MD

CONTACT

35052640; raymondtang@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 1. rectal indomethacin 100 mg to be administered before or after ERCP 2. a PD stent to be inserted during ERCP (a 3 to 5 cm 5Fr single pigtail pancreatic duct stent without inner flap is used, the stent is inserted after deep cannulation of pancreatic duct with a .025" or .035" wire) or 3. a PD stent plus rectal indomethacin 100 mg before or after ERCP In patients randomized to receive PD stenting, the number of attemtps is limited to 5.

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: October 22, 2018
• Study Start: March 21, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5); HK (1); TH (1)