Peripheral EBUS With ROSE vs no ROSE; Slim Bronchoscope Without Guide Sheath vs Standard Bronchoscope With Guide Sheath

Rapid On-site Evaluation and Use of a Slim Bronchoscope During Peripheral Endobronchial Ultrasonography for the Investigation of Peripheral Pulmonary Lesion - A Randomized Controlled Factorial Trial

Peripheral pulmonary lesions (PPL) are defined as nodules or masses that are located in the lung periphery; hence cannot be seen via regular bronchoscopy. Due to their location, establishing a pathological diagnosis can be challenging. Investigations of PPL has significantly evolved in the last decade with the development of new technologies such as peripheral endobronchial ultrasound (pEBUS), virtual bronchoscopy and electromagnetic navigational bronchoscopy (ENB). Although these technologies have allowed physicians to safely biopsy previously difficult to access nodules, their sensitivity have been lower than trans-thoracic needle aspiration (TTNA). In fact, the largest registry to date has found a diagnostic yield of pEBUS of 57% compared to 93% for TTNA. However, TTNA caries substantially more procedural risk than pEBUS with a 25% rate of complication vs 2.8% for pEBUS (1, 2). With increased sensitivity, pEBUS could become the procedure of choice for PPL investigation in view of its safety profile. Rapid on-site evaluation of biopsy samples by a cytopathologist (ROSE) allows for direct evaluation of specimen adequacy. By offering real-time feedback to the bronchoscopist about specimen adequacy, the adding of ROSE to pEBUS could lead to an increase in diagnostic yield, allowing for a faster diagnosis of lung cancer and avoiding the need for further diagnostic procedures. Minitiazuration of broncoscopes can also allow navigation to more distal areas of the lung closer to the PPL. While this may also improve diagnostic yield, other technical modification such as the need for smaller sampling instruments and inability to use a guide sheath may have drawbacks.

This study will use a 2 x 2 factorial design to compare diagnostic yield of pEBUS bronchoscopic PPL sampling with vs. without ROSE as well as with a novel "slim" bronchoscope vs. standard bronchoscope. The investigators aim to randomize 208 patients to independently test each hypothesis.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Cancer; Peripheral Pulmonary Lesions
• Intervention / Treatment: Procedure: Rapid on-site evaluation (ROSE); Procedure: Slim bronchoscope without a guide sheath; Procedure: Standard pEBUS with guide sheath

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada
    • Université Laval
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Health Sciences Centre

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adults ≥ 18 years old
2. Presence of a peripheral pulmonary lesion (PPL) of ≤5cm (mean short-long on axial CT) suspicious for malignancy.
3. The PPL appears radiologically accessible via pEBUS as assessed by an experienced interventional respirologist.
4. Absence of suspicious mediastinal lymphadenopathy on non-invasive staging defined as N1, N2 or N3 nodes ≥1cm on CT or ≥ moderate uptake on PET/CT unless shown to be negative on invasive sampling. Linear EBUS sampling of nodal stations will otherwise be permitted as part of a staging procedure.
5. Clinical decision made by patient and treating physician to proceed to bronchoscopy.

Exclusion Criteria:

1. Other intervention indicated as primary diagnostic procedure (eg: TTNA, surgical lung biopsy, linear EBUS alone, biopsy of extra-thoracic lesion)
2. Location of lesion not amenable to transbronchial needle aspiration sampling as assessed by an experienced interventional respirologist.
3. Contra-indication to pEBUS or bronchoscopy such as: severe pulmonary hypertension (mean pulmonary arterial pressure of ≥25mmHg with evidence of right heart failure), unstable medical condition or uncorrected coagulopathy.
4. Pregnancy
5. Use of electromagnetic or other navigation system (virtual bronchoscopic planning is allowed)
6. Absence of informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ROSE with guide sheath; Patients will undergo pEBUS with a regular size bronchoscope using the guide sheath technique and presence of ROSE	Procedure: Rapid on-site evaluation (ROSE); Pathologist on site for direct evaluation of specimen adequacy
Experimental: ROSE without guide sheath; Patients will undergo pEBUS with a slim bronchoscope combined with a 1.7mm radial probe but no guide sheath and the presence of ROSE.	Procedure: Rapid on-site evaluation (ROSE); Pathologist on site for direct evaluation of specimen adequacy; Procedure: Slim bronchoscope without a guide sheath; peripheral endobronchial ultrasound performed with a slim bronchoscope (3.0 mm outer diameter with a 1.7mm channel) combined with a radial ultrasound probe but without the use of a guide sheath.; Other Names: Ultrathin bronchoscope with pEBUS
Experimental: Guide sheath without ROSE; Patients will undergo pEBUS with a regular size bronchoscope using the guide sheath technique but without ROSE.	Procedure: Standard pEBUS with guide sheath; Using a flexible bronchoscope with minimal outer diameter of 4.2mm.
Experimental: No guide sheath without ROSE; Patients will undergo pEBUS with a slim bronchoscope combined with a 1.7mm radial probe but no the guide sheath an without the presence of ROSE.	Procedure: Slim bronchoscope without a guide sheath; peripheral endobronchial ultrasound performed with a slim bronchoscope (3.0 mm outer diameter with a 1.7mm channel) combined with a radial ultrasound probe but without the use of a guide sheath.; Other Names: Ultrathin bronchoscope with pEBUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peripheral pulmonary lesion diagnostic yield	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity for malignancy		weeks up to 1 month
Total procedure time		Intraoperative
Sample adequacy for adjunctive testing if lung cancer	Sample adequacy for EGFR mutation analysis, ALK and PDL1 immunohistochemistry.	1 month
Extra diagnostic procedure required for final diagnosis.		6 months up to 1 year
Complications	Combination of endpoints following chart review, including but not limited to unplanned hospitalization or emergency room visit, hemoptysis, pneumothorax, chest infection, fever or exacerbation of lung disease.	48 hours

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: McGill University; Laval University
• Investigators: Principal Investigator: Alain Tremblay, MDCM, University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Anticipated): March 30, 2024
• Study Completion (Anticipated): March 30, 2024

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 15, 2019
• First Posted (Actual): January 18, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: peripheral pulmonary lesion; peripheral endobronchial ultrasound; radial endobronchial ultrasound; guide sheath; ultrathin bronchoscope
• Other Study ID Numbers: 88888

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual deidentified participant data that underlie the results reported in this article (text, tables, figures and appendices) will be shared with researchers who provide a methodologically sound proposal. Other accessible documents will include the study protocol. Beginning 9 months and ending 36 months following article publications, proposals may be submitted to alain.tremblay@ucalgary.ca. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Time Frame: 9 to 36 months following article publication
• IPD Sharing Access Criteria: Shared with researchers who will provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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