Diagnostic Accuracy of ERCP-guided Versus Cholangioscopy-guided Tissue Acquisition in Patients With Indeterminate Biliary Strictures Suspected to be Intrinsic . (Cholangioscopy)

Diagnostic Accuracy of ERCP-guided Versus Cholangioscopy-guided Tissue Acquisition in Patients With Indeterminate Biliary Strictures Suspected to be Intrinsic - a Randomized Controlled Study

Primary Objective: To assess the diagnostic accuracy of cholangioscopy-based assessment using SpyDS technology compared to cholangiography-based assessment using ERCP-guided biopsy and brushing in patients with indeterminate biliary strictures in the setting of cholangiocarcinoma.

Study Overview

• Status: Unknown
• Conditions: Cholangiocarcinoma; Biliary Stricture
• Intervention / Treatment: Device: ERCP guided brushing and biopsy; Device: single operator cholangioscopy

Detailed Description

Study Design : Prospective,multi-center, randomized controlled, Post market Study (PMS)

Two groups:

• Control arm - ERCP arm: ERCP impression and ERCP-guided brushing and biopsy
• Study arm - Cholangioscopy arm: SpyDS impression and SpyDS-guided SpyBite biopsy Randomization 1:1 ratio. Primary Endpoint: Diagnostic accuracy of cholangioscopy or cholangiography assessed at 6 months after initial ERCP procedure
• Malignancy will be determined by cytology or histology on tissue sampling during the index procedure, or from other tissue acquisition or surgical specimen histopathology up to 6 months after the index procedure.
• Overall diagnostic accuracy.
• The assessed strictures will be considered benign if there was no confirmation of malignancy by 6 months after the index procedure.
• Overall diagnostic accuracy will be assessed for
• ERCP impression of malignancy
• ERCP-guided brushing and biopsies separately and combined*
• SpyDS impression of malignancy
• SpyBite biopsies
• In case of discordant results, the following will be followed for the combined pathology/cytology measure:
• If at least one is malignancy, then combine metric is malignant
• If both are benign or one is benign and one is non-diagnostic, then combined metric is benign
• If both are non-diagnostic, then combined metric is non-diagnostic

Secondary Endpoints:

1. Occurrence and severity of procedure related serious adverse events from index procedure through 30 days after procedure. Hospitalization and ICU admissions
2. Technical success of procedure defined as ability to collect tissue deemed adequate for cytology or histology. Indeterminate or equivocal or atypical or non-conclusive cytology or histology will be considered failures to this endpoint.
3. Correlation between impression of malignancy and cytopathology in the ERCP arm compared to the Cholangioscopy arm.
4. Additional diagnostic accuracy metrics: Sensitivity, specificity, positive predictive value, negative predictive value. The assessed strictures will be considered benign if there was no confirmation of malignancy by 6 months after the index procedure.
5. Impact of ERCP or cholangioscopy on patient management.
6. Need for additional diagnostic procedures beyond the index procedure.
7. Procedural measures: Type and number of devices used,
8. Duration of procedure from duodenoscope in to duodenoscope out

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohan Ramchandani, MD DM; Phone Number: 9701335444; Email: ramchandanimohan@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 or older.
2. Willing and able to comply with the study procedures and provide written informed consent to participate in the study
3. Biliary obstructive symptoms
4. Indeterminate biliary stricture suspected to be intrinsic based on prior imaging

Exclusion Criteria:

1. Contraindications for endoscopic techniques
2. Prior ERCP for assessment of indeterminate biliary stricture
3. Pancreatic head mass identified on prior non-invasive imaging and thought to be the cause of the biliary obstructive symptoms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control arm - ERCP arm; Control arm- If a patient is randomized to the Control arm, then the procedure will consist of the following: ERC with recording of ERC-based impression of malignancy .ERC-guided biopsies will be collected, consisting of 6 macroscopically visible biopsies. The biopsy forceps / brush will be selected per investigator preference. ERC-guided brushing will be performed, consisting of 10 through-and-fro passes through the target lesion. After this a biliary stent will be placed under ERC-guidance if needed. A biliary sphincterotomy will be performed as needed	Device: ERCP guided brushing and biopsy; • If patients are randomized to the Control arm, then they will undergo an ERCP. ERCP-based impression of malignancy (yes/no/indeterminate) will be recorded. ERCP-guided brushing and ERCP-guided biopsy will be performed.
Active Comparator: Study arm - cholangioscopy arm; If patient is randomized to the Study arm, then the procedure will consist of the following in order: Cannulation and sphincterotomy per standard of practice. POCS with recording of POCS-based impression of malignancy (yes/no/indeterminate). POCS will be performed using the Spy DS system. POCS-guided biopsies will be collected, consisting of 6 macroscopically visible biopsies. The POCS-guided biopsy forceps will be the SpyBite forceps.	Device: single operator cholangioscopy; If patient is randomized to the Study arm, then the procedure will consist of the following in order: Cannulation and sphincterotomy per standard of practice. POCS with recording of POCS-based impression of malignancy (yes/no/indeterminate). POCS will be performed using the Spy DS system. POCS-guided biopsies will be collected, consisting of 6 macroscopically visible biopsies. The POCS-guided biopsy forceps will be the SpyBite forceps.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of cholangioscopy or cholangiography	Malignancy will be determined by cytology or histology on tissue sampling during the index procedure, or from other tissue acquisition or surgical specimen histopathology up to 6 months after the index procedure.The assessed strictures will be considered benign if there was no confirmation of malignancy by 6 months after the index procedure. • Overall diagnostic accuracy will be assessed for ERCP impression of malignancy, ERCP-guided brushing and biopsies separately and combined, SpyDS impression of malignancy and SpyBite biopsies	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence and severity of procedure related serious adverse events	Occurrence and severity of procedure related serious adverse events from index procedure through 30 days after procedure.	30 days
Technical success of procedure	Technical success of procedure defined as ability to collect tissue deemed adequate for cytology or histology. Indeterminate or equivocal or atypical or non-conclusive cytology or histology will be considered failures to this endpoint	30 days
Additional diagnostic accuracy metrics: Sensitivity, specificity, positive predictive value, negative predictive value.	Additional diagnostic accuracy metrics: Sensitivity, specificity, positive predictive value, negative predictive value. The assessed strictures will be considered benign if there was no confirmation of malignancy by 6 months after the index procedure	6 months
Impact of ERCP or cholangioscopy on patient management.	Number of patients in whom management plan is altered based on ERCP or cholangioscopy will be determined	6 months
Number of patients needed additional diagnostic procedures beyond the index procedure for final diagnosis	Need for additional diagnostic procedures beyond the index procedure will be noted	6 months
Number of accessories used	The total number of accessories used during the procedure in both arms will be determined.	At index procedure.
Duration of procedure from duodenoscope in to duodenoscope out	Duration of procedure is defined as time from duodenoscope in to duodenoscope out	At index procedure
Correlation between impression of malignancy and cytopathology in the ERCP arm compared to the cholangioscopy arm	Number of participants will be compared for outcome of visual impression ( benign/ malignant disease) on ERCP or cholangioscopy with final out come of cytopathology in both arms.	6 months

Collaborators and Investigators

• Sponsor: Asian Institute of Gastroenterology, India
• Collaborators: Prince of Wales Hospital, Shatin, Hong Kong; Evangelisches Krankenhaus Düsseldorf
• Investigators: Principal Investigator: Mohan Ramchandani, MD DM, Asian Institute Of Gastroenterology

Publications and helpful links

General Publications

• Gerges C, Beyna T, Tang RSY, Bahin F, Lau JYW, van Geenen E, Neuhaus H, Nageshwar Reddy D, Ramchandani M. Digital single-operator peroral cholangioscopy-guided biopsy sampling versus ERCP-guided brushing for indeterminate biliary strictures: a prospective, randomized, multicenter trial (with video). Gastrointest Endosc. 2020 May;91(5):1105-1113. doi: 10.1016/j.gie.2019.11.025. Epub 2019 Nov 25.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 15, 2017
• Primary Completion (Anticipated): February 15, 2018
• Study Completion (Anticipated): June 15, 2018

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: May 2, 2017
• First Posted (Actual): May 4, 2017

Study Record Updates

• Last Update Posted (Actual): May 8, 2017
• Last Update Submitted That Met QC Criteria: May 4, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: ERCP; cholangioscopy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Pathological Conditions, Anatomical; Biliary Tract Diseases; Bile Duct Diseases; Constriction, Pathologic; Cholangiocarcinoma; Cholestasis
• Other Study ID Numbers: AIG-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No