Cryoprobe Versus Forceps for Transbronchial Biopsy (FROSTBITE-2)

A Randomized Trial of Cryoprobe Versus Forceps for Transbronchial Biopsy

The purpose of this study is to compare the effectiveness of transbronchial biopsy done by a 1.1mm cryoprobe versus the standard 2.0mm forceps.

Study Overview

• Status: Completed
• Conditions: Lung Diseases
• Intervention / Treatment: Device: ERBECRYO® 2 Cryosurgical Unit and Accessories - K190651; Device: Radial Jaw 4 Pulmonary Biopsy Forceps

Detailed Description

A smaller (1.1mm), flexible, single-use cryoprobe with an oversheath has been developed that can be used for transbronchial biopsies. This device has the potential to gather larger and higher quality tissue samples than the standard method using forceps, and with potentially fewer complications than older, larger versions of the cryoprobe.

For this study, patients will be randomized in a 1:1 fashion to transbronchial biopsy using a 1.1 mm cryoprobe versus 2.0 mm forceps, stratified by indication (evaluation of lung transplant allograft, diffuse parenchymal lung disease or pulmonary parenchymal lesion). Blinding of the proceduralist is not possible due to the nature of the procedure. Pathologists interpreting the biopsy samples will be blinded to the biopsy device used.

Patients enrolled in this study will have data collected by research staff for up to 30 days after the bronchoscopic biopsy procedure is performed. This 30-day follow-up period is the standard of care following bronchoscopic biopsy procedures.

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore (UMB)
  • Missouri
    • St Louis, Missouri, United States, 63130
      • Washington University in Saint Louis (Wash-U)
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • The Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center (VUMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or Female, ≥ 18-years-old
• Scheduled to undergo bronchoscopy with transbronchial biopsy per standard of care

Exclusion Criteria:

• Pregnant or nursing woman or woman of child-bearing potential who refuse to take a pregnancy test prior to enrollment
• Severe pulmonary hypertension (RVSP > 60 mmHg)
• Stroke within the last 6 months or myocardial infarction within the last 3 months
• Presence of bleeding disorder
• Platelet count < 50,000 per mL at time of enrollment
• Use of systemic anticoagulation or antiplatelet therapy without the ability to hold therapy for the recommended time prior to invasive procedure (aspirin monotherapy is acceptable)
• Do Not Resuscitate (DNR) status
• Do Not Intubate (DNI) status

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cryoprobe; Participants in this arm will undergo a standard of care bronchoscopy with a transbronchial biopsy using the 1.1mm sheath cryoprobe	Device: ERBECRYO® 2 Cryosurgical Unit and Accessories - K190651; ERBE 1.1mm flexible single-use cryoprobe with oversheath
Active Comparator: Forceps; Participants in this arm will undergo a standard of care bronchoscopy with a transbronchial biopsy using forceps	Device: Radial Jaw 4 Pulmonary Biopsy Forceps; Radial Jaw 4 Pulmonary Biopsy Forceps Standard Capacity for 2mm endoscope

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic yield as assessed by number of patients for which the procedure led to a diagnosis	Diagnostic Yield as Assessed by Number of Patients for Which the Procedure [Cryobiopsy or Forceps] Led to a Diagnosis.	During procedure, up to 1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic yield for pulmonary parenchymal lesions	Diagnostic Yield as Assessed by Number of Patients with pulmonary parenchymal lesions for Which the Procedure [Cryobiopsy or Forceps] Led to a Diagnosis.	During procedure, up to 1 hour
Diagnostic yield for diffuse parenchymal lung disease	Diagnostic Yield as Assessed by Number of Patients with diffuse parenchymal lung disease for Which the Procedure [Cryobiopsy or Forceps] Led to a Diagnosis.	During procedure, up to 1 hour
Diagnostic yield for Lung Transplant	Diagnostic Yield as Assessed by Number of Patients with a Lung Transplant for Which the Procedure [Cryobiopsy or Forceps] Led to a Diagnosis.	During procedure, up to 1 hour
Histological Accessibility grade of the biopsy specimen	7-point Likert scale: 0-6 with 0 being worse and 6 being best.	Participants assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
Bleeding Complication Rate	Number of occurrences of bleeding (grade ≥ 3 modified CTCAE).	Within 30 days of procedure
Pneumothorax Complication Rate	Number of occurrences of pneumothorax requiring chest tube placement (grade ≥ 2, CTCAE).	Within 30 days of procedure
Post-Procedure Respiratory Failure Rate	Number of occurrences of post-procedure respiratory failure (defined as the need for non-invasive or mechanical ventilation requiring ICU admission).	Within 30 days of procedure
Number of deaths	Number of occurrences of death.	Within 30 days of procedure
Total Histologic Area	Total Histologic Area in Square Millimeters.	Participants assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
Alveolated Area	Alveolated Area Square Millimeters	Participants assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
Percent Crush Artifact	Percent total area for Crush Artifact.	Participants assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
Artifact-free lung parenchyma	Percent Artifact-free lung parenchyma.	Participants assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
Adequacy for Molecular Testing	Assessed as a yes or no using Next Generation Sequencing (NGS).	Participants assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
Activation Time	Activation Time in Seconds.	At the time of procedure, up to 1 hour
Procedure Time	Procedure Time Seconds.	At the time of procedure, up to 1 hour

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Erbe USA Incorporated
• Investigators: Principal Investigator: Jeffrey Thiboutot, MD, MHS, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2023
• Primary Completion (Actual): March 2, 2026
• Study Completion (Actual): March 2, 2026

Study Registration Dates

• First Submitted: February 20, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Actual): March 2, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: lung; biopsy; bronchoscopic; cryoprobe
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases
• Other Study ID Numbers: IRB00344800

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: Yes
• product manufactured in and exported from the U.S.: Yes