Stent vs. Indomethacin for Preventing Post-ERCP Pancreatitis
Stent vs. Indomethacin for Preventing Post-ERCP Pancreatitis
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.
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:

 1. Clinical suspicion of or known sphincter of Oddi dysfunction

 2. History of post-ERCP pancreatitis (at least one prior episode of pancreatitis after
 ERCP)

 3. Pancreatic sphincterotomy

 4. Pre-cut (access) sphincterotomy (freehand pre-cut and septotomy)

 5. 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).

 6. Short-duration (≤ 1 min) balloon dilation of an intact biliary sphincter.

 Or has at least 2 of the following:

 7. Age < 50 years old & female gender

 8. History of recurrent pancreatitis (at least 2 episodes)

 9. ≥3 pancreatic injections

 10. Pancreatic acinarization

 11. Pancreatic brush cytology

 Exclusion Criteria:

 1. Ampullectomy

 2. Cases in which a pancreatic stent must be placed for therapeutic intent

 3. Unwillingness or inability to consent for the study

 4. Pregnancy

 5. Breast feeding mother

 6. Standard contraindications to ERCP

 7. Allergy to Aspirin or NSAIDs

 8. Known renal failure (Cr > 1.4 mg/dl)

 9. Ongoing or recent (within 2 weeks) hospitalization for gastrointestinal hemorrhage

 10. Ongoing or recent (within 1 week) hospitalization for acute pancreatitis

 11. Known chronic calcific pancreatitis

 12. Pancreatic head malignancy

 13. Procedure performed on major papilla/ventral pancreatic duct in patient with pancreas
 divisum (no manipulation of minor papilla)

 14. ERCP for biliary stent removal or exchange without anticipated pancreatogram

 15. Subjects with prior biliary sphincterotomy now scheduled for repeat biliary therapy
 without anticipated pancreatogram

 16. Anticipated inability to follow protocol

 17. Absence of rectum