Indeterminate Bile Duct StrictureNCT01580709
Endoscopic Retrograde Cholangiopancreatography (ERCP) Based Sampling of Indeterminate Bile Duct Strictures
A study testing Multiple brushings and Multimodality tissue sampling in people with Indeterminate Bile Duct Stricture, run by Medical University of South Carolina at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Indeterminate Bile Duct Stricture
- What is being tested?
- Multiple brushings and Multimodality tissue sampling
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2012to Sep 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Medical University of South Carolina
Charleston, South Carolina, 29425
Indiana University Health University Hospital
Indianapolis, Indiana, 46202
About this study
Official title: Optimizing the Role of ERCP in Evaluating Indeterminate Bile Duct Strictures
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
- Being tested
- Multiple brushings, Multimodality tissue sampling
- Keywords
- stricture, cholangiocarcinoma, pancreatic adenocarcinoma, bile duct, ERCP
- Medical subject headings
- Constriction, Pathologic, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multiple brushingsProcedure or surgery
Seven consecutive brush samples for cytology.
Multimodality tissue samplingProcedure or surgery
Single brush for cytology + single brush for FISH + cholangioscopy with site-directed biopsies
| Study group | Role | What they receive |
|---|---|---|
| Multimodality Approach | Active comparator | 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. Receives: Procedure: Multimodality tissue sampling |
| Multiple brush samples | Active comparator | 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). Receives: Procedure: Multiple brushings |
What is being measured
The primary outcome is the main question the study is designed to answer.
Performance characteristics
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."
Measured: 12 months
Secondary outcomes (2)
Incremental yield of multiple brushings
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.
Measured: 12 months
Incremental cost effectiveness ratio
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2012 (estimated)
- Study startApr 2012
- Primary completionSep 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Indeterminate Bile Duct StrictureStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Boston Scientific Corporation
- Responsible party
- Principal investigator, Gregory A. Cote, Medical University of South Carolina
- Investigators
- Gregory A Cote, MD, MS, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01580709
- Sponsor's protocol ID
- 10895519
- Other IDs
- K23DK095148
- Status last verified
- Sep 2016
- First submitted
- 17 Apr 2012
- Last updated
- 20 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimizing the Role of ERCP in Evaluating Indeterminate Bile Duct Strictures
- ClinicalTrials.gov ID
- NCT01580709
- Acronym / sponsor ID
- 10895519
- Conditions
- Indeterminate Bile Duct Stricture
- Keywords
- stricture, cholangiocarcinoma, pancreatic adenocarcinoma, bile duct, ERCP
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Boston Scientific Corporation
- Study start
- Apr 2012
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 19 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Multimodality Approach | Active comparator | Procedure: Multimodality tissue samplingPatients 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. |
| Multiple brush samples | Active comparator | Procedure: Multiple brushingsIn 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multiple brushingsSeven consecutive brush samples for cytology. | Procedure or surgery | Multiple brush samples |
| Multimodality tissue samplingSingle brush for cytology + single brush for FISH + cholangioscopy with site-directed biopsies | Procedure or surgery | Multimodality Approach |
Primary outcome
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."
2 secondary outcomes
Incremental yield of multiple brushings
Time frame: 12 months
Incremental cost effectiveness ratio
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2016.
Related trials for Indeterminate Bile Duct Stricture
Not yet recruitingObservational study
Spanish Registry of Direct Cholangiopancreatoscopy by Single Operator
Cholangiocarcinoma, Cholangiopathy
RecruitingObservational study
Bile Omics for Diagnosing Indeterminate Biliary Strictures
Cholangiocarcinoma, Gallbladder Cancer and Extrahepatic Cholangiocarcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory A Cote, MD, MS principal investigator
Medical University of South Carolina
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multiple brushings and Multimodality tissue sampling in people with Indeterminate Bile Duct Stricture, run by Medical University of South Carolina at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Performance characteristics (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2016.