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Endoscopic Retrograde Cholangiopancreatography (ERCP) Based Sampling of Indeterminate Bile Duct Strictures

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01580709
Recruitment Status : Completed
First Posted : April 19, 2012
Last Update Posted : September 20, 2016
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Boston Scientific Corporation
Information provided by (Responsible Party):
Gregory A. Cote, Medical University of South Carolina

Brief Summary:

Differentiating malignant from benign bile duct strictures is a conundrum, since no diagnostic test is highly sensitive for diagnosing cancer. While ERCP is effective in palliating obstructive jaundice, standard diagnostic tools in ERCP have a low diagnostic sensitivity and confirm the stricture's etiology in <50% of cases. During the first ERCP, standard practice is to obtain routine cytology (RC) using a single brush sample. If this is not diagnostic, patients often undergo repeat ERCP, endoscopic ultrasound or other, increasing health care costs. The incremental yield of performing alternate ERCP-based diagnostic tools during the first ERCP including fluorescence in situ hybridization (FISH), cholangioscopy w/biopsy and multiple brushes for routine cytology is currently unknown. There are no studies quantifying the amount of testing utilized to firmly diagnose the etiology of the stricture, or the most efficient combination of diagnostic tools during the first ERCP. These are important knowledge deficiencies since a definitive tissue diagnosis during the first ERCP could reduce the need for downstream tests and expedite treatment, thereby improving patient-centered and economic outcomes. The added costs of using multiple tools during the first ERCP may be offset by these benefits.

Among patients with indeterminate bile duct strictures, the investigators hypothesize that a multimodality approach will be more sensitive without a significant reduction in specificity compared to multiple brush samples for routine cytology. The investigators will test this hypothesis using an experimental trial design by randomizing patients during their first ERCP to multiple brushing samples for cytology vs. a single brush sample for cytology + FISH + cholangioscopy w/biopsy. To obtain preliminary data for a definitive multi-center trial, the investigators propose a pilot and feasibility study to compare the performance characteristics of each approach by evaluating the prospective clinical course, including treatment delay, quality of life, and life expectancy for each enrolled patient. If our hypothesis is validated in a subsequent definitive study, the standard approach to tissue sampling during the first ERCP may be altered.

Condition or disease Intervention/treatment Phase
Indeterminate Bile Duct Stricture Procedure: Multiple brushings Procedure: Multimodality tissue sampling Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Optimizing the Role of ERCP in Evaluating Indeterminate Bile Duct Strictures
Study Start Date : April 2012
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Multimodality Approach
Patients in the multimodality arm will undergo a single brushing for routine cytology, a second brush sample for Fluorescence In Situ Hybridization and a cholangioscopy with site-directed biopsies for histology.
Procedure: Multimodality tissue sampling
Single brush for cytology + single brush for FISH + cholangioscopy with site-directed biopsies

Active Comparator: Multiple brush samples
In patients randomized to multiple brushing samples, subsequent brushings #2-7 will be labeled separately and consecutively and sent to cytology. The cytopathologist will review each specimen for cellularity using a previously validated scoring system and presence of malignancy (positive, highly suspicious, atypical, normal).
Procedure: Multiple brushings
Seven consecutive brush samples for cytology.

Primary Outcome Measures :
  1. Performance characteristics [ Time Frame: 12 months ]

    A definite diagnosis of malignancy (i.e., "true positive") will be defined as either 1) a cytological or histological interpretation "positive for malignancy" based on brushing for RC or biopsy; 2) subsequent cytological or histological confirmation of malignancy within one year of the index procedure, via repeat ERCP, surgery, other diagnostic test.

    If a diagnosis of cancer is not confirmed after one year of follow-up, then the stricture will be classified as non-malignant and the negative cytology, FISH and histology from the index ERCP considered "true negatives."

Secondary Outcome Measures :
  1. Incremental yield of multiple brushings [ Time Frame: 12 months ]
    The additive role of each additional brushing will be analyzed for 1) adequacy of cellularity for cytological interpretation and 2) assessment of malignancy. The cytopathologist will be asked to interpret each of these outcomes using the first pass only (control group), first two passes only, first three passes only, and so on until all seven brushings are analyzed. The performance characteristics (see primary outcome) will be compared for each incremental brushing, assuming that a single intraductal brushing for RC is the reference standard.

  2. Incremental cost effectiveness ratio [ Time Frame: 12 months ]
    Complete data on medical utilization (e.g. hospitalizations, procedures, ambulatory visits) will be collected prospectively using Indiana Network for Patient Care (INPC) health information exchange databases (clinical electronic health record (EHR) and claims). Direct costs associated with the diagnostic evaluation of the indeterminate bile duct stricture (BDS) will be measured in both groups, including those costs associated with the index ERCP and all treatment costs associated with each study arm.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Extrahepatic BDS with no discrete mass on CT/MRI (either or both)
  • A BDS is defined as a segmental narrowing of the bile duct > 50% of the proximal or distal unaffected duct.
  • Biochemical evidence of cholestasis (increase in alkaline phosphatase ≥ 2x upper limit of normal ± total bilirubin ≥2.0mg/dL)

Exclusion Criteria:

  • No clinical suspicion for malignancy
  • Associated mass seen on CT or MRI
  • Age ≤18, pregnancy, incarceration, inability to give informed consent
  • Inability to undergo standard ERCP (e.g., postsurgical anatomy)
  • Previous ERCP with sampling of BDS, other than a single brushing specimen sent for routine cytopathology

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01580709

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United States, Indiana
Indiana University Health University Hospital
Indianapolis, Indiana, United States, 46202
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Medical University of South Carolina
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Boston Scientific Corporation
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Principal Investigator: Gregory A Cote, MD, MS Medical University of South Carolina
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Responsible Party: Gregory A. Cote, Principal Investigator, Medical University of South Carolina Identifier: NCT01580709    
Other Study ID Numbers: 10895519
K23DK095148 ( U.S. NIH Grant/Contract )
First Posted: April 19, 2012    Key Record Dates
Last Update Posted: September 20, 2016
Last Verified: September 2016
Keywords provided by Gregory A. Cote, Medical University of South Carolina:
pancreatic adenocarcinoma
bile duct
Additional relevant MeSH terms:
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Constriction, Pathologic
Pathological Conditions, Anatomical
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases