Stent vs. Indomethacin for Preventing Post-ERCP Pancreatitis

Study Overview
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Brief Summary
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Background: Pancreatitis is the most frequent complication of endoscopic retrograde cholangiopancreatography (ERCP), accounting for substantial morbidity, occasional mortality, and increased health care expenditures. Until recently, the only effective method of preventing post-ERCP pancreatitis (PEP) had been prophylactic pancreatic stent placement (PSP), an intervention that is costly, time consuming, technically challenging, and potentially dangerous. The investigators recently reported the results of a large randomized controlled trial demonstrating that rectal indomethacin, a non-steroidal anti-inflammatory drug, reduced the risk of pancreatitis after ERCP in high-risk patients, most of whom (>80%) had received a pancreatic stent. Secondary analysis of this RCT suggested that subjects who received indomethacin alone were less likely to develop PEP than those who received a pancreatic stent alone or the combination of indomethacin and stent, even after adjusting for underlying differences in subject risk. If indomethacin were to obviate the need for PSP, major clinical and cost benefits in ERCP practice could be realized. Objective: To assess whether rectal indomethacin alone is non-inferior to the combination of rectal indomethacin and prophylactic pancreatic stent placement for preventing post-ERCP pancreatitis in high-risk cases. Methods: Comparative effectiveness multi-center non-inferiority trial of rectal indomethacin alone vs. the combination of rectal indomethacin and prophylactic pancreatic stent placement for the prevention of post-ERCP pancreatitis in high-risk patients. One thousand four hundred and thirty subjects at elevated risk for PEP who would normally receive a pancreatic stent for prophylaxis will be randomized to indomethacin alone or the combination of indomethacin and PSP. The proportion of patients developing PEP and moderate-severe PEP will be compared. In addition, the investigators will establish a quality-assured central repository of biological specimens obtained from study participants, permitting future translational research elucidating the molecular and genetic mechanisms of PEP, as well as the mechanisms by which non-steroidal anti-inflammatory drugs prevent this complication.

Official Title
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Stent vs. Indomethacin for Preventing Post-ERCP Pancreatitis: The SVI Trial

Conditions
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Post-ERCP Pancreatitis

Intervention / Treatment
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* Other: Indomethacin 100 mg rectally immediately after ERCP, NO prophylactic pancreatic stent placement
* Other: Indomethacin 100 mg rectally immediately after ERCP AND prophylactic pancreatic stent placement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient undergoing ERCP in whom pancreatic stent placement is planned for post-ERCP pancreatitis prevention, is ≥ 18 years old, who provides informed consent, AND: Has one of the following: Clinical suspicion of or known sphincter of Oddi dysfunction History of post-ERCP pancreatitis (at least one prior episode of pancreatitis after ERCP) Pancreatic sphincterotomy Pre-cut (access) sphincterotomy (freehand pre-cut and septotomy) Difficult cannulation: cannulation duration ≥ 6 minutes (starting at time of initial papillary engagement with at least 25% of the time in contact with the papilla) AND/OR ≥ 6 cannulation attempts (defined as sustained contact with papilla lasting at least 1 second). Short-duration (≤ 1 min) balloon dilation of an intact biliary sphincter. Or has at least 2 of the following: Age < 50 years old & female gender History of recurrent pancreatitis (at least 2 episodes) ≥3 pancreatic injections Pancreatic acinarization Pancreatic brush cytology Exclusion Criteria: Ampullectomy Cases in which a pancreatic stent must be placed for therapeutic intent Unwillingness or inability to consent for the study Pregnancy Breast feeding mother Standard contraindications to ERCP Allergy to Aspirin or NSAIDs Known renal failure (Cr > 1.4 mg/dl) Ongoing or recent (within 2 weeks) hospitalization for gastrointestinal hemorrhage Ongoing or recent (within 1 week) hospitalization for acute pancreatitis Known chronic calcific pancreatitis Pancreatic head malignancy Procedure performed on major papilla/ventral pancreatic duct in patient with pancreas divisum (no manipulation of minor papilla) ERCP for biliary stent removal or exchange without anticipated pancreatogram Subjects with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram Anticipated inability to follow protocol Absence of rectum

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indomethacin alone<br>Indomethacin 100 mg rectally immediately after ERCP | Other: Indomethacin 100 mg rectally immediately after ERCP, NO prophylactic pancreatic stent placement<br> <br> |
| Active Comparator: Indomethacin+pancreatic stent<br>Indomethacin 100 mg rectally immediately after ERCP AND prophylactic pancreatic stent placement | Other: Indomethacin 100 mg rectally immediately after ERCP AND prophylactic pancreatic stent placement<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects in each study group with post-ERCP pancreatitis |  | Within 48 hours after ERCP | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects in each study group with moderate-severe post-ERCP pancreatitis |  | Within one month of ERCP |