Feasibility of Cryobiopsy from the Bile Duct - CRYLEO (CRYLEO)

Feasibility of in Vivo Percutaneous Cryobiopsy from the Human Bile Duct - CRYLEO

This is a multi-center, prospective, feasibility study using a 1.1 mm flexible cryoprobe SU via percutaneous access in the bile duct. The device has a CE-approval. First feasibility and safety for application assessed in the bile duct performed ex vivo and in a patient case report study. The study will take place at 5 different sites in Germany. Recruitment is competitive. In total, 15 patients will be enrolled. Patients are screened for study inclusion at the participating hospitals.

Primary objective:

• Feasibility of percutaneous cryobiopsy in the bile duct

Secondary objectives:

• Size of biopsy (mean area (in mm2) of each biopsy technique)
• Percentage of successful retrievals of biopsies by each biopsy technique
• Representativeness of each biopsy sample
• Quality of each biopsy sample
• Grade of crash artifacts occurrence defined as crush artifact area per biopsy
• Rate of safety-relevant aspects, like for example bleeding, post-bleeding, perforation, infection and abscess

Study Overview

• Status: Completed
• Conditions: Neoplasms, Bile Duct
• Intervention / Treatment: Device: 1.1mm flexible Cryoprobe SU

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, 45147
    • Klinikum Essen
  • Hamburg, Germany, 20246
    • Klinikum Hamburg
  • Hanau, Germany, 63450
    • Klinikum Hanau
  • Nürnberg, Germany, 90419
    • Klinikum Nürnberg
  • Stuttgart, Germany, 70174
    • Klinikum Stuttgart

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Suspicion of any neoplastic alterations in the bile duct system or other indication for biopsy sampling in the bile duct
• A percutaneous drainage or an access by means of percutaneous transhepatic cholangiodrainage (PTCD) has been previously established independent from study participation, without adverse events
• Patient is at least 18 years of age
• According to physicians' assessment, patient is able to follow study protocol or is able to understand the nature, objectives, benefits, implications, risks and inconveniences of the clinical investigation, able to comply with study requirements and understand and independently sign the Informed Consent Form

Exclusion Criteria:

• • Presence of hereditary bleeding disorder, e.g. hemophilia A or hemophilia B

  • Severe impairment of partial thromboplastin time (PTT) of >80s; International normalized ratio (INR) >3; platelet count <50,000 /nl
  • Dual antiplatelet therapy (change to aspirin monotherapy is no exclusion criterion)
  • Current use of systemic anticoagulation or antiplatelet therapy without the ability to hold therapy for the recommended amount of time prior to an invasive procedure (aspirin monotherapy is no exclusion criterion) Patient is participating in another clinical study pregnant or breast-feeding or intending to get pregnant during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Forceps biopsy against Cryoprobe biopsy; A total of 6 forceps biopsies and 3 cryobiopsies will be taken for each patient, corresponding to a 2:1 ratio. The biopsies are divided into blocks of two (6 forceps, 3 cryo). The biopsy technique blocks are randomized, resulting in a sequence of 6 forceps biopsies followed by 3 cryobiopsies	Device: 1.1mm flexible Cryoprobe SU; Six tissue samples retrieved by standard biopsy forceps and three samples by cryobiopsy (randomized sequence); Other Names: Comparator: SpyBite Max Forceps
Active Comparator: Cryoprobe biopsy against Forceps biopsy; A total of 6 forceps biopsies and 3 cryobiopsies will be taken for each patient, corresponding to a 2:1 ratio. The biopsies are divided into blocks of two (6 forceps, 3 cryo). The biopsy technique blocks are randomized, resulting in a sequence of 3 cryobiopsies followed by 6 forceps biopsies.	Device: 1.1mm flexible Cryoprobe SU; Six tissue samples retrieved by standard biopsy forceps and three samples by cryobiopsy (randomized sequence); Other Names: Comparator: SpyBite Max Forceps

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary endpoint of this study is feasibility of percutaneous cryobiopsy in the bile duct, i.e., successful retrieval of at least one cryobiopsy specimen per patient.	Feasibility of percutaneous cryobiopsy in the bile duct, i.e., successful retrieval of at least one cryobiopsy specimen per patient	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Size of biopsy (mean area (in mm2) of each biopsy technique)	Quality of biopsies	30 days
Percentage of successful retrievals of biopsies by each biopsy technique	Quality of biopsies	30 days
Representativeness of each biopsy sample	yes: evaluable bile duct epithelia in sufficient quantity and quality to make a diagnosis or no: absent or not sufficiently evaluable bile duct epithelia (e.g. crush artefacts, dissolved tissue association	30 days
Quality of each biopsy sample	Biopsy quality using a Likert-Scale for each biopsy technique	30 days
Grade of crash artifacts occurrence defined as crush artifact area per biopsy	Quality of biopsies	30 days
Rate of safety-relevant aspects, like for example bleeding, post-bleeding, perforation, infection and abscess	Quality of biopsies	30 days

Collaborators and Investigators

• Sponsor: Erbe Elektromedizin GmbH

Publications and helpful links

General Publications

• Peveling-Oberhag J, Zimmermann C, Linzenbold W, Ott G, Enderle M, Albert JG. Bile duct tissue acquisition by cholangioscopy-guided cryobiopsy technique: first-in-human application. VideoGIE. 2023 Feb 15;8(4):158-161. doi: 10.1016/j.vgie.2022.12.007. eCollection 2023 Apr.
• Walter D, Peveling-Oberhag J, Schulze F, Bon D, Zeuzem S, Friedrich-Rust M, Albert JG. Intraductal biopsies in indeterminate biliary stricture: Evaluation of histopathological criteria in fluoroscopy- vs. cholangioscopy guided technique. Dig Liver Dis. 2016 Jul;48(7):765-70. doi: 10.1016/j.dld.2016.03.013. Epub 2016 Mar 26.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Actual): August 30, 2024
• Study Completion (Actual): August 30, 2024

Study Registration Dates

• First Submitted: January 5, 2024
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 22, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Biliary Tract Neoplasms; Bile Duct Neoplasms
• Other Study ID Numbers: CIV-23-06-043299

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No