Post-ERCP PancreatitisPhase 2/3NCT01912716
Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis
A Phase 2/3 study testing high dose indomethacin and standard dose indomethacin in people with Post-ERCP Pancreatitis, run by Indiana University at 6 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post-ERCP Pancreatitis
- What is being tested?
- high dose indomethacin and standard dose indomethacin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,037 participants
- Where
- 6 sitesUnited States
- Study dates
- Jul 2013to Oct 2018
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 15Show fewer
- 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 -
Who cannot join
- 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)
Show all 17Show fewer
- 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 -
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Michigan Medical Center
Ann Arbor, Michigan, 48109
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Medical University of South Carolina
Charleston, South Carolina, 29425
Methodist Dallas Medical Center
Dallas, Texas, 75203
Indiana University Health
Indianapolis, Indiana, 46202
Aurora St. Lukes' Medical Center
Milwaukee, Wisconsin, 53220
About this study
Official title: Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis in High Risk Patients: Searching for the Optimal Dose. A Prospective, Randomized Trial
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.
Read the 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.
- Conditions
- Post-ERCP Pancreatitis
- Being tested
- high dose indomethacin, standard dose indomethacin
- Keywords
- pancreatitis, ERCP
- Medical subject headings
- Pancreatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
high dose indomethacinDrug
Also called Indocin
patients randomized to this intervention receive 200mg indomethacin
standard dose indomethacinDrug
Also called Indocin
patients randomized to this intervention receive 100mg indomethacin
| Study group | Role | What they receive |
|---|---|---|
| high-dose indomethacin | Experimental | 200mg rectal indomethacin Receives: Drug: high dose indomethacin |
| standard dose indomethacin | Active comparator | 100mg rectal indomethacin Receives: Drug: standard dose indomethacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 days
Secondary outcomes (1)
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).
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionApr 2018
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-ERCP PancreatitisStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,037 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Principal investigator, Evan Fogel, Indiana University
- Investigators
- Evan L Fogel, MD, MSc, Principal investigator, Indiana University Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01912716
- Sponsor's protocol ID
- PEP INDO 2013
- Other IDs
- ACG-CR-002-2013
- Status last verified
- Jun 2019
- First submitted
- 29 Jul 2013
- Last updated
- 5 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 31780277
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis in High Risk Patients: Searching for the Optimal Dose. A Prospective, Randomized Trial
- ClinicalTrials.gov ID
- NCT01912716
- Acronym / sponsor ID
- PEP INDO 2013
- Conditions
- Post-ERCP Pancreatitis
- Keywords
- pancreatitis, ERCP
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,037 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- 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
- Study start
- Jul 2013
- Primary completion
- Apr 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 31 Jul 2013 (estimated)
- Results
- Posted 18 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| high-dose indomethacin | Experimental | Drug: high dose indomethacin200mg rectal indomethacin |
| standard dose indomethacin | Active comparator | Drug: standard dose indomethacin100mg rectal indomethacin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Included patients are those undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) and have:
- 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
Key exclusion criteria (17 listed)
- Unwillingness or inability to consent for the study
- Age less than 18 years
- Intrauterine pregnancy
- Breastfeeding mother
- Standard contraindications to ERCP
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| high dose indomethacinAlso: Indocinpatients randomized to this intervention receive 200mg indomethacin | Drug | high-dose indomethacin |
| standard dose indomethacinAlso: Indocinpatients randomized to this intervention receive 100mg indomethacin | Drug | standard dose indomethacin |
Primary outcome
Number of Participants Who Developed Post-ERCP Pancreatitis
Time frame: 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.
1 secondary outcome
Number of Participants With Moderate or Severe Post-ERCP Pancreatitis
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31780277Fogel 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Evan L Fogel, MD, MSc principal investigator
Indiana University Health
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing high dose indomethacin and standard dose indomethacin in people with Post-ERCP Pancreatitis, run by Indiana University at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Developed Post-ERCP Pancreatitis (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01912716, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2019.