Post-ERCP Pancreatitis
Conditions
Brief summary
Pancreatitis (inflammation of the pancreas) is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), a procedure for the diagnosis and treatment of disorders of the pancreas and bile duct. Preliminary data has shown that non-steroidal antiinflammatory drugs, when administered rectally, can reduce the risk of pancreatitis after ERCP. This study is intended to definitively determine whether rectally administered indomethacin (a non-steroidal antiinflammatory drug)is effective at preventing pancreatitis after ERCP.
Detailed description
This study is a multi-center, randomized, placebo-controlled, double-blinded clinical trial of rectal indomethacin in the prevention of post-ERCP pancreatitis in high risk patients.
Interventions
DRUGIndomethacin
100 mg PR once at the time of ERCP
2 placebo suppositories at the time of ERCP
Sponsors
Indiana University School of Medicine
University of Kentucky
Case Western Reserve University
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Included patients are those undergoing ERCP and have one of the following: 1. Clinical suspicion of sphincter of Oddi dysfunction 2. History of post-ERCP pancreatitis (at least one episode) 3. Pancreatic sphincterotomy 4. Pre-cut (access) sphincterotomy 5. \> 8 cannulation attempts 6. Pneumatic dilation of intact biliary sphincter 7. Ampullectomy or at least 2 of the following: 1. Age \< 50 years old & female gender 2. History of recurrent pancreatitis (at least 2 episodes) 3. ≥3 pancreatic injections, with at least one injection to tail 4. Pancreatic acinarization 5. Pancreatic brush cytology
Exclusion criteria
1. Unwillingness or inability to consent for the study 2. Age \< 18 years 3. Intrauterine pregnancy 4. Breast feeding mother 5. Standard contraindications to ERCP 6. Allergy to Aspirin or NSAIDs 7. Renal failure (Cr \> 1.4) 8. Active or recent (within 4 weeks) gastrointestinal hemorrhage 9. Acute pancreatitis (lipase peak) within 72 hours 10. Known chronic calcific pancreatitis 11. Pancreatic head malignancy 12. Procedure performed on major papilla/ventral panc duct in pt with pancreas divisum (no manipulation of minor papilla) 13. ERCP for biliary stent removal or exchange without anticipated pancreatogram 14. Subjects with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram 15. Anticipated inability to follow protocol 16. Endoscopist discretion: low risk (\<10%) of post-ERCP pancreatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-ERCP Pancreatitis | 5 days | Subjects were diagnosed with post-ERCP pancreatitis if they experienced new upper abdominal pain, pancreatic enzyme elevation at least three times the upper limit of normal 24 hours after the procedure, and hospitalization of at least two nights. |
Countries
United States
Participant flow
Recruitment details
Between February 2009 and July 2011, 602 subjects were enrolled at 4 university-affiliated medical centers in the United States.
Pre-assignment details
Of the 799 consented subjects, 169 were not randomized because an inclusion criterion was not met, 11 were not randomized because an exclusion criterion was met, and 17 were not randomized because ERCP not performed.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 2 placebo suppositories. The suppositories were administered immediately after ERCP while the patient was still in the procedure room. | 307 |
| Indomethacin 2 50-mg indomethacin suppositories. The suppositories were administered immediately after ERCP while the patient was still in the procedure room. | 295 |
| Total | 602 |
Baseline characteristics
| Characteristic | Indomethacin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 27 Participants | 50 Participants |
| Age, Categorical Between 18 and 65 years | 272 Participants | 280 Participants | 552 Participants |
| Age Continuous | 44.5 years STANDARD_DEVIATION 13.5 | 46.0 years STANDARD_DEVIATION 13.1 | 45.3 years STANDARD_DEVIATION 13.3 |
| Region of Enrollment United States | 295 participants | 307 participants | 602 participants |
| Sex: Female, Male Female | 229 Participants | 247 Participants | 476 Participants |
| Sex: Female, Male Male | 66 Participants | 60 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 307 | 0 / 295 |
| serious Total, serious adverse events | 61 / 307 | 31 / 295 |
Outcome results
Primary
Post-ERCP Pancreatitis
Subjects were diagnosed with post-ERCP pancreatitis if they experienced new upper abdominal pain, pancreatic enzyme elevation at least three times the upper limit of normal 24 hours after the procedure, and hospitalization of at least two nights.
Time frame: 5 days
Population: 100% completed follow-up
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo | Post-ERCP Pancreatitis | 52 participants | 37.6 |
| Indomethacin | Post-ERCP Pancreatitis | 27 participants | 28.9 |