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

NCT ID: NCT01580709

Last Updated: 2016-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2016-09-30

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.

Conditions

Indeterminate Bile Duct Stricture

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Multimodality tissue sampling

Intervention Type: PROCEDURE

Single brush for cytology + single brush for FISH + cholangioscopy with site-directed biopsies

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).

Group Type: ACTIVE_COMPARATOR

Multiple brushings

Intervention Type: PROCEDURE

Seven consecutive brush samples for cytology.

Interventions

Multiple brushings

Seven consecutive brush samples for cytology.

Intervention Type: PROCEDURE

Multimodality tissue sampling

Single brush for cytology + single brush for FISH + cholangioscopy with site-directed biopsies

Intervention Type: PROCEDURE

Eligibility 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

• 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

Boston Scientific Corporation

INDUSTRY

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Gregory A. Cote

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gregory A Cote, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Indiana University Health University Hospital

Indianapolis, Indiana, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

Other Identifiers

K23DK095148

Identifier Type: NIH

Identifier Source: secondary_id

View Link

10895519

Identifier Type: -

Identifier Source: org_study_id