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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Peripheral Pulmonary Lesions, Lung Cancer

Intervention / Treatment
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* Procedure: Rapid on-site evaluation (ROSE)
* Procedure: Slim bronchoscope without a guide sheath
* Procedure: Standard pEBUS with guide sheath


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 18 years old Presence of a peripheral pulmonary lesion (PPL) of ≤5cm (mean short-long on axial CT) suspicious for malignancy. The PPL appears radiologically accessible via pEBUS as assessed by an experienced interventional respirologist. 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. Clinical decision made by patient and treating physician to proceed to bronchoscopy. Exclusion Criteria: Other intervention indicated as primary diagnostic procedure (eg: TTNA, surgical lung biopsy, linear EBUS alone, biopsy of extra-thoracic lesion) Location of lesion not amenable to transbronchial needle aspiration sampling as assessed by an experienced interventional respirologist. 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. Pregnancy Use of electromagnetic or other navigation system (virtual bronchoscopic planning is allowed) Absence of informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ROSE with guide sheath<br>Patients will undergo pEBUS with a regular size bronchoscope using the guide sheath technique and presence of ROSE | Procedure: Rapid on-site evaluation (ROSE)<br>* Pathologist on site for direct evaluation of specimen adequacy<br>|
| Experimental: ROSE without guide sheath<br>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)<br>* Pathologist on site for direct evaluation of specimen adequacy<br>Procedure: Slim bronchoscope without a guide sheath<br>* 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.<br>* Other names: Ultrathin bronchoscope with pEBUS;|
| Experimental: Guide sheath without ROSE<br>Patients will undergo pEBUS with a regular size bronchoscope using the guide sheath technique but without ROSE. | Procedure: Standard pEBUS with guide sheath<br>* Using a flexible bronchoscope with minimal outer diameter of 4.2mm.<br>|
| Experimental: No guide sheath without ROSE<br>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<br>* 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.<br>* Other names: Ultrathin bronchoscope with pEBUS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral endobronchial ultrasound, radial endobronchial ultrasound, guide sheath, ultrathin bronchoscope, peripheral pulmonary lesion