Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis

Post-ERCP Pancreatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01912716
• Other study ID #: PEP INDO 2013
• Secondary ID: ACG-CR-002-2013
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 2013
• Est. completion date: October 2018

Study information

• Verified date: June 2019
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1037
• Est. completion date: October 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 -

Related Conditions & MeSH terms

• Pancreatitis
• Post-ERCP Pancreatitis

Intervention

Drug:
• high dose indomethacin
patients randomized to this intervention receive 200mg indomethacin
• standard dose indomethacin
patients randomized to this intervention receive 100mg indomethacin

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Methodist Dallas Medical Center	Dallas	Texas
United States	Indiana University Health	Indianapolis	Indiana
United States	Aurora St. Lukes' Medical Center	Milwaukee	Wisconsin

Sponsors (7)

Lead Sponsor	Collaborator
Indiana University	American College of Gastroenterology, Aurora Health Care, Beth Israel Deaconess Medical Center, Medical University of South Carolina, University of Michigan, University of Texas

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Developed Post-ERCP Pancreatitis	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	Number of Participants With Moderate or Severe Post-ERCP Pancreatitis	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