Clinical trial NCT01912716: Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis
Official title: Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis in High Risk Patients: Searching for the Optimal Dose. A Prospective, Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Post-ERCP Pancreatitis
Keywords: pancreatitis
ERCP
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: American College of Gastroenterology
name: University of Michigan
name: University of Texas
name: Wake Forest University Health Sciences
name: Medical University of South Carolina
name: Beth Israel Deaconess Medical Center
First posted: 2013-07-31
Enrollment: 1037
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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 -

Primary outcomes:
measure: Number of Participants Who Developed Post-ERCP Pancreatitis
timeFrame: 5 days
Secondary outcomes:
measure: Number of Participants With Moderate or Severe Post-ERCP Pancreatitis
timeFrame: 30 days
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Methodist Dallas Medical Center
state: Texas
city: Milwaukee
country: United States
facility: Aurora St. Lukes' Medical Center
state: Wisconsin
Study officials:
affiliation: Indiana University Health
name: Evan L Fogel, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fogel EL, Lehman GA, Tarnasky P, Cote GA, Schmidt SE, Waljee AK, Higgins PDR, Watkins JL, Sherman S, Kwon RSY, Elta GH, Easler JJ, Pleskow DK, Scheiman JM, El Hajj II, Guda NM, Gromski MA, McHenry L Jr, Arol S, Korsnes S, Suarez AL, Spitzer R, Miller M, Hofbauer M, Elmunzer BJ; US Cooperative for Outcomes Research in Endoscopy (USCORE). Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial. Lancet Gastroenterol Hepatol. 2020 Feb;5(2):132-141. doi: 10.1016/S2468-1253(19)30337-1. Epub 2019 Nov 25.