Rectal Indomethacin in the Prevention of Post-endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis in High Risk Patients

A Prospective, Randomized, Controlled Trial of Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis in High Risk Patients.

Pancreatitis (inflammation of the pancreas) is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), a procedure for the diagnosis and treatment of disorders of the pancreas and bile duct.

Preliminary data has shown that non-steroidal antiinflammatory drugs, when administered rectally, can reduce the risk of pancreatitis after ERCP. This study is intended to definitively determine whether rectally administered indomethacin (a non-steroidal antiinflammatory drug)is effective at preventing pancreatitis after ERCP.

Study Overview

• Status: Terminated
• Conditions: Post-ERCP Pancreatitis
• Intervention / Treatment: Drug: Indomethacin; Other: Placebo suppositories

Detailed Description

This study is a multi-center, randomized, placebo-controlled, double-blinded clinical trial of rectal indomethacin in the prevention of post-ERCP pancreatitis in high risk patients.

• Study Type: Interventional
• Enrollment (Actual): 602
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center

Participation Criteria

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 ERCP and have one of the following:

1. Clinical suspicion of sphincter of Oddi dysfunction
2. History of post-ERCP pancreatitis (at least one episode)
3. Pancreatic sphincterotomy
4. Pre-cut (access) sphincterotomy
5. > 8 cannulation attempts
6. Pneumatic dilation of intact biliary sphincter
7. Ampullectomy

or at least 2 of the following:

1. Age < 50 years old & female gender
2. History of recurrent pancreatitis (at least 2 episodes)
3. ≥3 pancreatic injections, with at least one injection to tail
4. Pancreatic acinarization
5. Pancreatic brush cytology

Exclusion Criteria:

1. Unwillingness or inability to consent for the study
2. Age < 18 years
3. Intrauterine pregnancy
4. Breast feeding mother
5. Standard contraindications to ERCP
6. Allergy to Aspirin or NSAIDs
7. Renal failure (Cr > 1.4)
8. Active or recent (within 4 weeks) gastrointestinal hemorrhage
9. Acute pancreatitis (lipase peak) within 72 hours
10. Known chronic calcific pancreatitis
11. Pancreatic head malignancy
12. Procedure performed on major papilla/ventral panc duct in pt with pancreas divisum (no manipulation of minor papilla)
13. ERCP for biliary stent removal or exchange without anticipated pancreatogram
14. Subjects with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram
15. Anticipated inability to follow protocol
16. Endoscopist discretion: low risk (<10%) of post-ERCP pancreatitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; Indomethacin suppository	Drug: Indomethacin; 100 mg PR once at the time of ERCP
PLACEBO_COMPARATOR: 2; Placebo suppository	Other: Placebo suppositories; 2 placebo suppositories at the time of ERCP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-ERCP Pancreatitis	Subjects were diagnosed with post-ERCP pancreatitis if they experienced new upper abdominal pain, pancreatic enzyme elevation at least three times the upper limit of normal 24 hours after the procedure, and hospitalization of at least two nights.	5 days

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: University of Kentucky; Case Western Reserve University; Indiana University School of Medicine
• Investigators: Principal Investigator: Badih J Elmunzer, MD, University of Michigan

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): July 1, 2011
• Study Completion (ACTUAL): July 1, 2011

Study Registration Dates

• First Submitted: January 9, 2009
• First Submitted That Met QC Criteria: January 9, 2009
• First Posted (ESTIMATE): January 12, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): February 28, 2013
• Last Update Submitted That Met QC Criteria: February 21, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Reproductive Control Agents; Gout Suppressants; Tocolytic Agents; Indomethacin
• Other Study ID Numbers: HUM00022847