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

December 14, 2023 updated by: James Yun-wong Lau, Chinese University of Hong Kong

Comparative Effectiveness Between Rectally Administered Indomethacin and Pancreatic Stenting in the Prevention of Post Endoscopic Retrograde Cholangio-panceaticography (ERCP) Pancreatitis: a Randomized Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background of research

Pancreatitis is the most common complication after Endoscopic retrograde cholangiopancreatography (ERCP). It occurs in approximately 5% of patients. The risk can approach 20 to 30% in those with known pre- and intra-procedural risk factors. Three in 100 patients with post ERCP pancreatitis (PEP) consequently die. The placement of pancreatic duct stent and the use of rectal administered indomethacin have both been independently shown to reduce PEP. The placement of a pancreatic duct stent has been for a long time considered the gold standard in the prophylaxis against PEP. In a meta-analysis of 8 RCTs that compared the use of pancreatic duct stents to no treatment, pancreatic duct stenting in high risk patients reduces incidence of PEP by approximately 5 fold. In a landmark study by Elmunzer et al., rectal administered indomethacin was shown to reduce PEP (52 of 307 patients,16.9% to 27 of 295 patients, 9.2%, P=0.005). In the trial, >80% received pancreatic duct stents in addition to rectal indomethacin. Overall there have been 7 RCTs on the use of rectal indomethacin all showing benefits with its use, 3 with PDS and 4 without. In the literature, there has been no direct comparison between the use of rectal indomethacin alone and insertion of PDS. In a secondary analysis of the trial by Elmunzer et al., PEP following the use of rectal indomethacin alone was less compared with the placement of PDS. In a meta-analysis by Akbar et al. pooling 29 studies (22 PDS and 7 indomethacin), the use of rectal indomethacin alone was associated with fewer PEP when compared to insertion of PDS on an indirect comparison using network metaanalysis (OR 0.48, 95%CI 0.26-0.87). The more favorable results with rectal indomethacin alone raised the question if PDS insertion is necessary. Furthermore, in another secondary analysis, patients after failed PDS insertion had a 34.7% rate of pancreatitis. In contrary, the rate of pancreatitis was 16.4% in those after successful PDS and 12.1% after no attempt at PDS insertion. The SVI (stent versus indomethacin) trial (NCT024762279) by the US cooperative for Outcomes Research in Endoscopy (USCORE) group is an ongoing non-inferiority trial that compares indomethacin alone to the combination of indomethacin and PDS in 1430 high risk patients with the primary outcome of pancreatitis. The trial tests the hypothesis that PDS is no longer necessary in the context of rectal indomethacin.

The rationale for the trial has been based on the secondary analysis of the Elmunzer trial and the network analysis aforementioned.

The investigators argue that the relative merits of rectal indomethacin and PDS placement have not been established. There may have been substantial difference in the baseline risks between the trials using either rectal indomethacin and PDS placement alone. The small number of RCTs over the use of rectal indomethacin may have overestimated its beneficial effect especially among patients at lower risk of PEP. A direct comparison in the form of a RCT to compare effectiveness of both treatment modalities is required. The insertion of PDS may continue to be important in patients contraindicated for the use of NSAIDs.

Research plan and methodology The investigators hypothesize that rectal administration of indomethacin is not inferior to placement of a pancreatic duct stent in the prevention of pancreatitis after ERCP in high risk patients. In patients randomised to receive pancreatic duct stents, the investigators sought to determine the success rate with PDS insertion and outcomes following successful or unsuccessful PDS insertion. In addition, the investigators analyse possible factors to PEP in both cohorts of patients on either indomethacin or PDS.

Study Type

Interventional

Enrollment (Estimated)

1734

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shan XI
      • Xi'an, Shan XI, China, 710000
        • Recruiting
        • Endoscopy centre
        • Contact:
        • Sub-Investigator:
          • Pang Yang Lin, MD
        • Principal Investigator:
          • Kai Chun Wu, MD
    • Shanghai
      • Shanghai, Shanghai, China, 200000
        • Recruiting
        • Eastern Hepatobiliary Surgery Hospital,Endoscopy centre
        • Contact:
        • Principal Investigator:
          • Bing Hu, MD
      • Shanghai, Shanghai, China, 200000
        • Not yet recruiting
        • Endoscopy centre
        • Contact:
        • Principal Investigator:
          • YU Bai, MD
    • Tian Jin
      • Tianjin, Tian Jin, China, 300000
        • Recruiting
        • Endoscopy centre
        • Contact:
        • Principal Investigator:
          • Wen Li, MD
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310013
        • Recruiting
        • Endoscopy centre
        • Contact:
        • Principal Investigator:
          • Yun sheng Qing, MD
  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Endoscopy Centre, Prince of Wales Hospital
        • Contact:
  • Thailand
      • Bangkok, Thailand
        • Recruiting
        • 2. Chulalongkorn University and King Chulalongkorn Memorial Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

presence of one of the following risk factors for Post ERCP Pancreatitis

  1. sphincter of Oddi dysfunction
  2. history of PEP, pancreatic instrumentation or sphincterotomy, precut sphincterotomy,
  3. difficult cannulation defined by >5 cannulation attempts
  4. the use of double wire technique in bile duct access
  5. 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: indomethacin
rectal indomethacin 100 mg to be administered before or after ERCP
Drug: Indomethacin
rectally administered indomethacin before or after ERCP
Other Names:
  • indocid
Experimental: pancreatic stenting
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
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)
Experimental: indomethacin plus pancreatic stenting
[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]
Drug: Indomethacin
rectally administered indomethacin before or after ERCP
Other Names:
  • indocid
Device: pancreatic stenting
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
post-ERCP pancreatitis
Time Frame: 30 days
Percentage of Participants with post ERCP pancreatitis
30 days
high severity of post-ERCP pancreatitis
Time Frame: 30 days

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
Time Frame: 30 days
Percentage of Participants with pancreatitis with complications using Atlanta classification (Mild / Moderate / Severe / Critical )
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
hospital stay
Time Frame: 30 days
period of hospitalisation (days)
30 days
endoscopic intervention due to PEP
Time Frame: 30 days
Percentage of Participants with endoscopic intervention due to Post ERCP pancreatitis
30 days
radiologic intervention due to PEP
Time Frame: 30 days
Percentage of Participants with radiologic intervention due to Post ERCP pancreatitis
30 days
surgery due to PEP
Time Frame: 30 days
Percentage of Participants with Surgical intervention due to Post ERCP pancreatitis
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Collaborators

Xijing Hospital
Changhai Hospital
Eastern Hepatobiliary Surgery Hospital
Zhejiang University
Tianjin Union Medical Center

Investigators

  • Principal Investigator: James LAU, MD, Chinese University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 21, 2019

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

August 23, 2018

First Submitted That Met QC Criteria

October 18, 2018

First Posted (Actual)

October 22, 2018

Study Record Updates

Last Update Posted (Estimated)

December 15, 2023

Last Update Submitted That Met QC Criteria

December 14, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • StentvsNSAID

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Post ERCP Pancreatitis

Clinical Trials on Indomethacin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Colombia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe