Clinical trial NCT02476279: Stent vs. Indomethacin for Preventing Post-ERCP Pancreatitis
Official title: Stent vs. Indomethacin for Preventing Post-ERCP Pancreatitis: The SVI Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-ERCP Pancreatitis
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2015-06-19
Enrollment: 1950
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Background: Pancreatitis is the most frequent complication of endoscopic retrograde cholangiopancreatography (ERCP), accounting for substantial morbidity, occasional mortality, and increased health care expenditures. Until recently, the only effective method of preventing post-ERCP pancreatitis (PEP) had been prophylactic pancreatic stent placement (PSP), an intervention that is costly, time consuming, technically challenging, and potentially dangerous. The investigators recently reported the results of a large randomized controlled trial demonstrating that rectal indomethacin, a non-steroidal anti-inflammatory drug, reduced the risk of pancreatitis after ERCP in high-risk patients, most of whom (\>80%) had received a pancreatic stent. Secondary analysis of this RCT suggested that subjects who received indomethacin alone were less likely to develop PEP than those who received a pancreatic stent alone or the combination of indomethacin and stent, even after adjusting for underlying differences in subject risk. If indomethacin were to obviate the need for PSP, major clinical and cost benefits in ERCP practice could be realized.

Objective: To assess whether rectal indomethacin alone is non-inferior to the combination of rectal indomethacin and prophylactic pancreatic stent placement for preventing post-ERCP pancreatitis in high-risk cases.

Methods: Comparative effectiveness multi-center non-inferiority trial of rectal indomethacin alone vs. the combination of rectal indomethacin and prophylactic pancreatic stent placement for the prevention of post-ERCP pancreatitis in high-risk patients. One thousand four hundred and thirty subjects at elevated risk for PEP who would normally receive a pancreatic stent for prophylaxis will be randomized to indomethacin alone or the combination of indomethacin and PSP. The proportion of patients developing PEP and moderate-severe PEP will be compared. In addition, the investigators will establish a quality-assured central repository of biological specimens obtained from study participants, permitting future translational research elucidating the molecular and genetic mechanisms of PEP, as well as the mechanisms by which non-steroidal anti-inflammatory drugs prevent this complication.

Detailed description: The purpose of the SVI study is to determine whether or not rectal indomethacin has no important loss of efficacy as compared to the combination of rectal indomethacin and prophylactic pancreatic stent placement in patients undergoing high-risk ERCP who require pancreatic stent placement (PSP) for the sole purpose of pancreatitis prevention. The primary efficacy endpoint is defined as post-ERCP pancreatitis defined per consensus (Altanta) criteria. Another way of stating the trial's purpose is that the proportion of subjects with post-ERCP pancreatitis on rectal indomethacin alone is not more than that of the combination of rectal indomethacin and prophylactic PSP by more than a pre-specified absolute amount (i.e., the non-inferiority margin).

This is a blinded, two-armed non-inferiority trial where eligible patients will be randomized to either the combination treatment or indomethacin alone. Participants will be randomized during the ERCP procedure after eligibility is confirmed, and receive indomethacin at the time of randomization. The primary efficacy endpoint of post-ERCP pancreatitis within 2 days from randomization will be assessed by an independent adjudication panel. The participant follow-up period is 30 days from randomization.

Eligibility criteria: Inclusion Criteria:

Any patient undergoing ERCP in whom pancreatic stent placement is planned for post-ERCP pancreatitis prevention, is ≥ 18 years old, who provides informed consent, AND:

Has one of the following:

1. Clinical suspicion of or known sphincter of Oddi dysfunction
2. History of post-ERCP pancreatitis (at least one prior episode of pancreatitis after ERCP)
3. Pancreatic sphincterotomy
4. Pre-cut (access) sphincterotomy (freehand pre-cut and septotomy)
5. Difficult cannulation: cannulation duration ≥ 6 minutes (starting at time of initial papillary engagement with at least 25% of the time in contact with the papilla) AND/OR ≥ 6 cannulation attempts (defined as sustained contact with papilla lasting at least 1 second).
6. Short-duration (≤ 1 min) balloon dilation of an intact biliary sphincter.

   Or has at least 2 of the following:
7. Age \< 50 years old \& female gender
8. History of recurrent pancreatitis (at least 2 episodes)
9. ≥3 pancreatic injections
10. Pancreatic acinarization
11. Pancreatic brush cytology

Exclusion Criteria:

1. Ampullectomy
2. Cases in which a pancreatic stent must be placed for therapeutic intent
3. Unwillingness or inability to consent for the study
4. Pregnancy
5. Breast feeding mother
6. Standard contraindications to ERCP
7. Allergy to Aspirin or NSAIDs
8. Known renal failure (Cr \> 1.4 mg/dl)
9. Ongoing or recent (within 2 weeks) hospitalization for gastrointestinal hemorrhage
10. Ongoing or recent (within 1 week) hospitalization for acute pancreatitis
11. Known chronic calcific pancreatitis
12. Pancreatic head malignancy
13. Procedure performed on major papilla/ventral pancreatic duct in patient with pancreas divisum (no manipulation of minor papilla)
14. ERCP for biliary stent removal or exchange without anticipated pancreatogram
15. Subjects with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram
16. Anticipated inability to follow protocol
17. Absence of rectum

Primary outcomes:
measure: The Proportion of Subjects in Each Study Group With Post-ERCP Pancreatitis
timeFrame: Within 48 hours after ERCP
Secondary outcomes:
measure: The Proportion of Subjects in Each Study Group With Moderate-severe Post-ERCP Pancreatitis
timeFrame: Within one month of ERCP
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Univesrity of Southern California
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Orlando
country: United States
facility: The Florida Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth University
state: New Hampshire
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: University of Calgary
city: Montreal
country: Canada
facility: McGill University
Study officials:
References:
citation: Elmunzer BJ, Serrano J, Chak A, Edmundowicz SA, Papachristou GI, Scheiman JM, Singh VK, Varadarajulu S, Vargo JJ, Willingham FF, Baron TH, Cote GA, Romagnuolo J, Wood-Williams A, Depue EK, Spitzer RL, Spino C, Foster LD, Durkalski V; SVI study group and the United States Cooperative for Outcomes Research in Endoscopy (USCORE). Rectal indomethacin alone versus indomethacin and prophylactic pancreatic stent placement for preventing pancreatitis after ERCP: study protocol for a randomized controlled trial. Trials. 2016 Mar 3;17(1):120. doi: 10.1186/s13063-016-1251-2.