Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis

June 24, 2019 updated by: Evan Fogel, Indiana University

Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis in High Risk Patients: Searching for the Optimal Dose. A Prospective, Randomized Trial

It is now established that indomethacin, a non-steroidal anti-inflammatory drug, at a dose of 100 mg, is effective in reducing the frequency and severity of pancreatitis (inflammation of the pancreas) after endoscopic retrograde cholangiopancreatography (ERCP) in high risk patients. However, the optimal dose required is not known. The purpose of this study is to determine whether a dose of 200 mg, administered as rectal suppositories, is more effective than the standard dose of 100 mg. An ERCP procedure is a scope procedure where a lighted tube with a camera is passed down the patient's throat and allows for evaluation of the bile duct and/or pancreatic duct. The most common side effect of this procedure is post-ERCP pancreatitis, or swelling of the pancreas. Some patients are at higher risk for this complication than others. Our hypothesis is to compare the efficacy of these two dose regimens (100 mg vs 200 mg) of prophylactic rectally-administered indomethacin on the frequency and severity of post-ERCP pancreatitis in high-risk patients.

Study Overview

Detailed Description

After obtaining informed consent, subjects will undergo ERCP per clinical protocol. All procedure-related clinical decisions and interventions will be dictated by the performing physician as he or she sees fit. At the end of the procedure, it will be determined by the endoscopist and research coordinator whether the patient meets inclusion criteria. If inclusion criteria are met, subjects will be randomized by concealed allocation to receive either 100mg or 150mg indomethacin, in the form of two or three 50mg rectal suppositories. Those patients who are randomized to receive the 100mg dose will receive an additional glycerin suppository. Four hours later, those patients who were randomized to the high-dose group will then receive an additional 50mg suppository while in the recovery area. At this same time point, subjects who were randomized to the standard-dose group, will receive a glycerin suppository in the recovery area. All participating patients will receive a total of 4 suppositories.

Study Type

Interventional

Enrollment (Actual)

1037

Phase

  • Phase 2
  • 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 Locations

    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Medical Center
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Texas
      • Dallas, Texas, United States, 75203
        • Methodist Dallas Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53220
        • Aurora St. Lukes' Medical Center

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Included patients are those undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) and have:

one of the following:

  1. Clinical suspicion of sphincter of Oddi dysfunction (SOD; type I or II)
  2. History of post-ERCP pancreatitis (at least one episode)
  3. Pancreatic sphincterotomy
  4. Pre-cut (access) sphincterotomy
  5. greater than 8 cannulation attempts of any sphincter
  6. Pneumatic dilation of intact biliary sphincter
  7. Ampullectomy 8.) Assessment for post-sphincterotomy stenosis

OR at least 2 of the following:

  1. Age less than 50 years old and female gender
  2. History of recurrent pancreatitis (at least 2 episodes)
  3. greater than or equal to to 3 pancreatic injections, with at least 1 injection to tail
  4. Pancreatic acinarization (excluding ventral pancreas of pancreas divisum)
  5. Pancreatic brush cytology -

Exclusion Criteria:

  1. Unwillingness or inability to consent for the study
  2. Age less than 18 years
  3. Intrauterine pregnancy
  4. Breastfeeding mother
  5. Standard contraindications to ERCP
  6. Allergy/hypersensitivity to aspirin or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
  7. Received NSAIDs in prior 7 days (aspirin 325mg or less ok)
  8. Renal failure (serum creatinine greater than 1.4)
  9. Active or recurrent (within 4 weeks) gastrointestinal hemorrhage
  10. Acute pancreatitis (lipase peak) within 72 hours
  11. Known chronic calcific pancreatitis
  12. Pancreatic head mass
  13. Procedure performed on major papilla/ventral pancreatic duct in patient with pancreas divisum (dorsal duct not attempted on injected)
  14. ERCP for biliary stent removal or exchange without anticipated pancreatogram
  15. Subject with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram
  16. Anticipated inability to follow protocol
  17. Known active cardiovascular or cerebrovascular disease -

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: high-dose indomethacin
200mg rectal indomethacin
patients randomized to this intervention receive 200mg indomethacin
Other Names:
  • Indocin
Active Comparator: standard dose indomethacin
100mg rectal indomethacin
patients randomized to this intervention receive 100mg indomethacin
Other Names:
  • Indocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Developed Post-ERCP Pancreatitis
Time Frame: 5 days
Assessment of whether patients developed post-ERCP pancreatitis, defined as a new onset of pain (or worsening of existing pain) in the upper abdomen, an elevation in pancreatic enzymes of at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least two nights.
5 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Moderate or Severe Post-ERCP Pancreatitis
Time Frame: 30 days
Assessment of whether patients developed either moderate or severe post-ERCP pancreatitis, defined according to established consensus criteria (Cotton et al., Gastrointestinal Endoscopy 1991;37:383-93). Severity of post-ERCP pancreatitis is partly defined according to length of stay. Moderate pancreatitis is defined as a 4-10 day hospitalization. Severe post-ERCP pancreatitis is defined as a hospitalization of greater than 10 days post-ERCP, or development of a complication (eg. pseudocyst or necrosis), or need for intervention (drainage or surgery).
30 days

Collaborators and Investigators

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

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.

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

July 1, 2013

Primary Completion (Actual)

April 1, 2018

Study Completion (Actual)

October 1, 2018

Study Registration Dates

First Submitted

July 29, 2013

First Submitted That Met QC Criteria

July 30, 2013

First Posted (Estimate)

July 31, 2013

Study Record Updates

Last Update Posted (Actual)

July 5, 2019

Last Update Submitted That Met QC Criteria

June 24, 2019

Last Verified

June 1, 2019

More Information

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.

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