Stent vs. Indomethacin for Preventing Post-ERCP Pancreatitis

NCT ID: NCT02476279

Last Updated: 2024-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1950 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2023-01-25

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.

Conditions

Post-ERCP Pancreatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Indomethacin alone

Indomethacin 100 mg rectally immediately after ERCP

Group Type: EXPERIMENTAL

Indomethacin 100 mg rectally immediately after ERCP, NO prophylactic pancreatic stent placement

Intervention Type: OTHER

Indomethacin+pancreatic stent

Indomethacin 100 mg rectally immediately after ERCP AND prophylactic pancreatic stent placement

Group Type: ACTIVE_COMPARATOR

Indomethacin 100 mg rectally immediately after ERCP AND prophylactic pancreatic stent placement

Intervention Type: OTHER

Interventions

Indomethacin 100 mg rectally immediately after ERCP, NO prophylactic pancreatic stent placement

Intervention Type: OTHER

Indomethacin 100 mg rectally immediately after ERCP AND prophylactic pancreatic stent placement

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Badih Joseph Elmunzer

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Univesrity of Southern California

Los Angeles, California, United States

University of Colorado

Denver, Colorado, United States

The Florida Hospital

Orlando, Florida, United States

Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

University of Kansas

Kansas City, Kansas, United States

Johns Hopkins University

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Washington University

St Louis, Missouri, United States

Dartmouth University

Lebanon, New Hampshire, United States

Case Western Reserve University

Cleveland, Ohio, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University

Nashville, Tennessee, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

University of Calgary

Calgary, , Canada

McGill University

Montreal, , Canada

Countries

United States; Canada

References

Elmunzer BJ, Foster LD, Serrano J, Cote GA, Edmundowicz SA, Wani S, Shah R, Bang JY, Varadarajulu S, Singh VK, Khashab M, Kwon RS, Scheiman JM, Willingham FF, Keilin SA, Papachristou GI, Chak A, Slivka A, Mullady D, Kushnir V, Buxbaum J, Keswani R, Gardner TB, Forbes N, Rastogi A, Ross A, Law J, Yachimski P, Chen YI, Barkun A, Smith ZL, Petersen B, Wang AY, Saltzman JR, Spitzer RL, Ordiah C, Spino C, Durkalski-Mauldin V; SVI Study Group. Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial. Lancet. 2024 Feb 3;403(10425):450-458. doi: 10.1016/S0140-6736(23)02356-5. Epub 2024 Jan 11.

Reference Type: DERIVED

PMID: 38219767 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26941086 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U01DK104833-01

Identifier Type: NIH

Identifier Source: secondary_id

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U01DK104833-01

Identifier Type: NIH

Identifier Source: org_study_id

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