Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis
Primary Purpose
Post-ERCP Pancreatitis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
high dose indomethacin
standard dose indomethacin
Sponsored by
About this trial
This is an interventional prevention trial for Post-ERCP Pancreatitis focused on measuring pancreatitis, ERCP
Eligibility Criteria
Inclusion Criteria:
Included patients are those undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) and have:
one of the following:
- Clinical suspicion of sphincter of Oddi dysfunction (SOD; type I or II)
- History of post-ERCP pancreatitis (at least one episode)
- Pancreatic sphincterotomy
- Pre-cut (access) sphincterotomy
- greater than 8 cannulation attempts of any sphincter
- Pneumatic dilation of intact biliary sphincter
- Ampullectomy 8.) Assessment for post-sphincterotomy stenosis
OR at least 2 of the following:
- Age less than 50 years old and female gender
- History of recurrent pancreatitis (at least 2 episodes)
- greater than or equal to to 3 pancreatic injections, with at least 1 injection to tail
- Pancreatic acinarization (excluding ventral pancreas of pancreas divisum)
- Pancreatic brush cytology -
Exclusion Criteria:
- Unwillingness or inability to consent for the study
- Age less than 18 years
- Intrauterine pregnancy
- Breastfeeding mother
- Standard contraindications to ERCP
- Allergy/hypersensitivity to aspirin or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
- Received NSAIDs in prior 7 days (aspirin 325mg or less ok)
- Renal failure (serum creatinine greater than 1.4)
- Active or recurrent (within 4 weeks) gastrointestinal hemorrhage
- Acute pancreatitis (lipase peak) within 72 hours
- Known chronic calcific pancreatitis
- Pancreatic head mass
- Procedure performed on major papilla/ventral pancreatic duct in patient with pancreas divisum (dorsal duct not attempted on injected)
- ERCP for biliary stent removal or exchange without anticipated pancreatogram
- Subject with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram
- Anticipated inability to follow protocol
- Known active cardiovascular or cerebrovascular disease -
Sites / Locations
- Indiana University Health
- Beth Israel Deaconess Medical Center
- University of Michigan Medical Center
- Medical University of South Carolina
- Methodist Dallas Medical Center
- Aurora St. Lukes' Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
high-dose indomethacin
standard dose indomethacin
Arm Description
200mg rectal indomethacin
100mg rectal indomethacin
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
Full Information
NCT ID
NCT01912716
First Posted
July 29, 2013
Last Updated
June 24, 2019
Sponsor
Indiana University
Collaborators
American College of Gastroenterology, University of Michigan, University of Texas, Aurora Health Care, Medical University of South Carolina, Beth Israel Deaconess Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT01912716
Brief Title
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
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
April 2018 (Actual)
Study Completion Date
October 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indiana University
Collaborators
American College of Gastroenterology, University of Michigan, University of Texas, Aurora Health Care, Medical University of South Carolina, Beth Israel Deaconess Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-ERCP Pancreatitis
Keywords
pancreatitis, ERCP
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1037 (Actual)
8. Arms, Groups, and Interventions
Arm Title
high-dose indomethacin
Arm Type
Experimental
Arm Description
200mg rectal indomethacin
Arm Title
standard dose indomethacin
Arm Type
Active Comparator
Arm Description
100mg rectal indomethacin
Intervention Type
Drug
Intervention Name(s)
high dose indomethacin
Other Intervention Name(s)
Indocin
Intervention Description
patients randomized to this intervention receive 200mg indomethacin
Intervention Type
Drug
Intervention Name(s)
standard dose indomethacin
Other Intervention Name(s)
Indocin
Intervention Description
patients randomized to this intervention receive 100mg indomethacin
Primary Outcome Measure Information:
Title
Number of Participants Who Developed Post-ERCP Pancreatitis
Description
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.
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Number of Participants With Moderate or Severe Post-ERCP Pancreatitis
Description
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).
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Included patients are those undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) and have:
one of the following:
Clinical suspicion of sphincter of Oddi dysfunction (SOD; type I or II)
History of post-ERCP pancreatitis (at least one episode)
Pancreatic sphincterotomy
Pre-cut (access) sphincterotomy
greater than 8 cannulation attempts of any sphincter
Pneumatic dilation of intact biliary sphincter
Ampullectomy 8.) Assessment for post-sphincterotomy stenosis
OR at least 2 of the following:
Age less than 50 years old and female gender
History of recurrent pancreatitis (at least 2 episodes)
greater than or equal to to 3 pancreatic injections, with at least 1 injection to tail
Pancreatic acinarization (excluding ventral pancreas of pancreas divisum)
Pancreatic brush cytology -
Exclusion Criteria:
Unwillingness or inability to consent for the study
Age less than 18 years
Intrauterine pregnancy
Breastfeeding mother
Standard contraindications to ERCP
Allergy/hypersensitivity to aspirin or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Received NSAIDs in prior 7 days (aspirin 325mg or less ok)
Renal failure (serum creatinine greater than 1.4)
Active or recurrent (within 4 weeks) gastrointestinal hemorrhage
Acute pancreatitis (lipase peak) within 72 hours
Known chronic calcific pancreatitis
Pancreatic head mass
Procedure performed on major papilla/ventral pancreatic duct in patient with pancreas divisum (dorsal duct not attempted on injected)
ERCP for biliary stent removal or exchange without anticipated pancreatogram
Subject with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram
Anticipated inability to follow protocol
Known active cardiovascular or cerebrovascular disease -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Evan L Fogel, MD, MSc
Organizational Affiliation
Indiana University Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University Health
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Methodist Dallas Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75203
Country
United States
Facility Name
Aurora St. Lukes' Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53220
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
31780277
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.
Results Reference
derived
Learn more about this trial
Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis
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