Post-ERCP Pancreatitis
Conditions
Keywords
pancreatitis, ERCP
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.
Interventions
DRUGhigh dose indomethacin
patients randomized to this intervention receive 200mg indomethacin
patients randomized to this intervention receive 100mg indomethacin
Sponsors
American College of Gastroenterology
University of Michigan
University of Texas
Wake Forest University Health Sciences
Medical University of South Carolina
Beth Israel Deaconess Medical Center
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Developed Post-ERCP Pancreatitis | 5 days | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Moderate or Severe Post-ERCP Pancreatitis | 30 days | 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). |
Countries
United States
Participant flow
Recruitment details
Patients were recruited between July 2013 - March 2018, either from the ERCP (Endoscopic Retrograde Cholangiopancreatography) outpatient clinic or Peri-Operative Care Unit immediately prior to ERCP.
Participants by arm
| Arm | Count |
|---|---|
| Standard Dose Group Participants randomized to this group receive 100 mg indomethacin | 515 |
| High Dose Group Participants randomized to this group receive 200 mg indomethacin | 522 |
| Total | 1,037 |
Baseline characteristics
| Characteristic | Standard Dose Group | High Dose Group | Total |
|---|---|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 15.2 | 50.4 years STANDARD_DEVIATION 15 | 49.9 years STANDARD_DEVIATION 15.1 |
| Ampullectomy | 30 Participants | 32 Participants | 62 Participants |
| Biliary sphincterotomy | 302 Participants | 290 Participants | 592 Participants |
| BMI | 28.6 kg/m^2 STANDARD_DEVIATION 7 | 29.2 kg/m^2 STANDARD_DEVIATION 7.6 | 28.9 kg/m^2 STANDARD_DEVIATION 7.3 |
| Clinical Suspicion of SOD (sphincter of Oddi dysfunction) | 319 Participants | 331 Participants | 650 Participants |
| Difficult Cannulation | 148 Participants | 146 Participants | 294 Participants |
| Double-wire cannulation technique | 18 Participants | 18 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 15 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 493 Participants | 507 Participants | 1000 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| History of post-ERCP pancreatitis | 77 Participants | 100 Participants | 177 Participants |
| History of recurrent pancreatitis | 202 Participants | 210 Participants | 412 Participants |
| Number of pancreatic duct injections | 2.12 injections STANDARD_DEVIATION 1.63 | 1.96 injections STANDARD_DEVIATION 1.66 | 2.04 injections STANDARD_DEVIATION 1.64 |
| Obese | 193 Participants | 198 Participants | 391 Participants |
| Pancreatography (patients) | 446 Participants | 433 Participants | 879 Participants |
| Placement of pancreatic stent | 400 Participants | 393 Participants | 793 Participants |
| Precut sphincterotomy | 71 Participants | 46 Participants | 117 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 12 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 4 Participants | 13 Participants |
| Race (NIH/OMB) White | 485 Participants | 501 Participants | 986 Participants |
| Sex: Female, Male Female | 392 Participants | 421 Participants | 813 Participants |
| Sex: Female, Male Male | 123 Participants | 101 Participants | 224 Participants |
| Therapeutic pancreatic sphincterotomy | 245 Participants | 231 Participants | 476 Participants |
| Trainee involvement | 84 Participants | 68 Participants | 152 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 515 | 0 / 522 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 83 / 515 | 77 / 522 |
Outcome results
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.
Time frame: 5 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard 100mg Dose | Number of Participants Who Developed Post-ERCP Pancreatitis | 76 Participants |
| High Dose 200 mg | Number of Participants Who Developed Post-ERCP Pancreatitis | 65 Participants |
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).
Time frame: 30 days
Population: development of moderate or severe post-ERCP pancreatitis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard 100mg Dose | Number of Participants With Moderate or Severe Post-ERCP Pancreatitis | 28 Participants |
| High Dose 200 mg | Number of Participants With Moderate or Severe Post-ERCP Pancreatitis | 28 Participants |