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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Indiana University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT01580709
First received: April 17, 2012
Last updated: April 16, 2013
Last verified: April 2013
  Purpose

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 Intervention
Indeterminate Bile Duct Stricture
Procedure: Multiple brushings
Procedure: Multimodality tissue sampling

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Optimizing the Role of ERCP in Evaluating Indeterminate Bile Duct Strictures

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Performance characteristics [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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:
  • Incremental yield of multiple brushings [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • Incremental cost effectiveness ratio [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 50
Study Start Date: April 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01580709

Contacts
Contact: Sheryl Lynch, BSN 317-944-4228 slynch@iupui.edu

Locations
United States, Indiana
Indiana University Health University Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
Investigators
Principal Investigator: Gregory A Cote, MD, MS Indiana University
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT01580709     History of Changes
Other Study ID Numbers: 10895519, 1K23DK095148-01
Study First Received: April 17, 2012
Last Updated: April 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
stricture
cholangiocarcinoma
pancreatic adenocarcinoma
bile duct
ERCP

Additional relevant MeSH terms:
Constriction, Pathologic
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on August 26, 2014