<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03809169</url>
  </required_header>
  <id_info>
    <org_study_id>88888</org_study_id>
    <nct_id>NCT03809169</nct_id>
  </id_info>
  <brief_title>Peripheral EBUS With ROSE vs no ROSE; Slim Bronchoscope Without Guide Sheath vs Standard Bronchoscope With Guide Sheath</brief_title>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>McGill University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Laval University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Calgary</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Peripheral pulmonary lesions (PPL) are defined as nodules or masses that are located in the&#xD;
      lung periphery; hence cannot be seen via regular bronchoscopy. Due to their location,&#xD;
      establishing a pathological diagnosis can be challenging. Investigations of PPL has&#xD;
      significantly evolved in the last decade with the development of new technologies such as&#xD;
      peripheral endobronchial ultrasound (pEBUS), virtual bronchoscopy and electromagnetic&#xD;
      navigational bronchoscopy (ENB). Although these technologies have allowed physicians to&#xD;
      safely biopsy previously difficult to access nodules, their sensitivity have been lower than&#xD;
      trans-thoracic needle aspiration (TTNA). In fact, the largest registry to date has found a&#xD;
      diagnostic yield of pEBUS of 57% compared to 93% for TTNA. However, TTNA caries substantially&#xD;
      more procedural risk than pEBUS with a 25% rate of complication vs 2.8% for pEBUS (1, 2).&#xD;
      With increased sensitivity, pEBUS could become the procedure of choice for PPL investigation&#xD;
      in view of its safety profile. Rapid on-site evaluation of biopsy samples by a&#xD;
      cytopathologist (ROSE) allows for direct evaluation of specimen adequacy. By offering&#xD;
      real-time feedback to the bronchoscopist about specimen adequacy, the adding of ROSE to pEBUS&#xD;
      could lead to an increase in diagnostic yield, allowing for a faster diagnosis of lung cancer&#xD;
      and avoiding the need for further diagnostic procedures. Minitiazuration of broncoscopes can&#xD;
      also allow navigation to more distal areas of the lung closer to the PPL. While this may also&#xD;
      improve diagnostic yield, other technical modification such as the need for smaller sampling&#xD;
      instruments and inability to use a guide sheath may have drawbacks.&#xD;
&#xD;
      This study will use a 2 x 2 factorial design to compare diagnostic yield of pEBUS&#xD;
      bronchoscopic PPL sampling with vs. without ROSE as well as with a novel &quot;slim&quot; bronchoscope&#xD;
      vs. standard bronchoscope. The investigators aim to randomize 208 patients to independently&#xD;
      test each hypothesis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 1, 2019</start_date>
  <completion_date type="Anticipated">March 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 30, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Peripheral pulmonary lesion diagnostic yield</measure>
    <time_frame>1 month</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sensitivity and specificity for malignancy</measure>
    <time_frame>weeks up to 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total procedure time</measure>
    <time_frame>Intraoperative</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sample adequacy for adjunctive testing if lung cancer</measure>
    <time_frame>1 month</time_frame>
    <description>Sample adequacy for EGFR mutation analysis, ALK and PDL1 immunohistochemistry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extra diagnostic procedure required for final diagnosis.</measure>
    <time_frame>6 months up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complications</measure>
    <time_frame>48 hours</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">186</enrollment>
  <condition>Peripheral Pulmonary Lesions</condition>
  <condition>Lung Cancer</condition>
  <arm_group>
    <arm_group_label>ROSE with guide sheath</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will undergo pEBUS with a regular size bronchoscope using the guide sheath technique and presence of ROSE</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ROSE without guide sheath</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will undergo pEBUS with a slim bronchoscope combined with a 1.7mm radial probe but no guide sheath and the presence of ROSE.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Guide sheath without ROSE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will undergo pEBUS with a regular size bronchoscope using the guide sheath technique but without ROSE.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No guide sheath without ROSE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Rapid on-site evaluation (ROSE)</intervention_name>
    <description>Pathologist on site for direct evaluation of specimen adequacy</description>
    <arm_group_label>ROSE with guide sheath</arm_group_label>
    <arm_group_label>ROSE without guide sheath</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Slim bronchoscope without a guide sheath</intervention_name>
    <description>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.</description>
    <arm_group_label>No guide sheath without ROSE</arm_group_label>
    <arm_group_label>ROSE without guide sheath</arm_group_label>
    <other_name>Ultrathin bronchoscope with pEBUS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Standard pEBUS with guide sheath</intervention_name>
    <description>Using a flexible bronchoscope with minimal outer diameter of 4.2mm.</description>
    <arm_group_label>Guide sheath without ROSE</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adults ≥ 18 years old&#xD;
&#xD;
          2. Presence of a peripheral pulmonary lesion (PPL) of ≤5cm (mean short-long on axial CT)&#xD;
             suspicious for malignancy.&#xD;
&#xD;
          3. The PPL appears radiologically accessible via pEBUS as assessed by an experienced&#xD;
             interventional respirologist.&#xD;
&#xD;
          4. Absence of suspicious mediastinal lymphadenopathy on non-invasive staging defined as&#xD;
             N1, N2 or N3 nodes ≥1cm on CT or ≥ moderate uptake on PET/CT unless shown to be&#xD;
             negative on invasive sampling. Linear EBUS sampling of nodal stations will otherwise&#xD;
             be permitted as part of a staging procedure.&#xD;
&#xD;
          5. Clinical decision made by patient and treating physician to proceed to bronchoscopy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Other intervention indicated as primary diagnostic procedure (eg: TTNA, surgical lung&#xD;
             biopsy, linear EBUS alone, biopsy of extra-thoracic lesion)&#xD;
&#xD;
          2. Location of lesion not amenable to transbronchial needle aspiration sampling as&#xD;
             assessed by an experienced interventional respirologist.&#xD;
&#xD;
          3. Contra-indication to pEBUS or bronchoscopy such as: severe pulmonary hypertension&#xD;
             (mean pulmonary arterial pressure of ≥25mmHg with evidence of right heart failure),&#xD;
             unstable medical condition or uncorrected coagulopathy.&#xD;
&#xD;
          4. Pregnancy&#xD;
&#xD;
          5. Use of electromagnetic or other navigation system (virtual bronchoscopic planning is&#xD;
             allowed)&#xD;
&#xD;
          6. Absence of informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alain Tremblay, MDCM</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Health Sciences Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universite Laval</name>
      <address>
        <city>Quebec</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>May 10, 2023</last_update_submitted>
  <last_update_submitted_qc>May 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>peripheral endobronchial ultrasound</keyword>
  <keyword>radial endobronchial ultrasound</keyword>
  <keyword>guide sheath</keyword>
  <keyword>ultrathin bronchoscope</keyword>
  <keyword>peripheral pulmonary lesion</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>9 to 36 months following article publication</ipd_time_frame>
    <ipd_access_criteria>Shared with researchers who will provide a methodologically sound proposal.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03809169
org study id: 88888
nct id: NCT03809169
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Peripheral pulmonary lesion diagnostic yield
time frame: 1 month
measure: Sensitivity and specificity for malignancy
time frame: weeks up to 1 month
measure: Total procedure time
time frame: Intraoperative
measure: Sample adequacy for adjunctive testing if lung cancer
time frame: 1 month
description: Sample adequacy for EGFR mutation analysis, ALK and PDL1 immunohistochemistry.
measure: Extra diagnostic procedure required for final diagnosis.
time frame: 6 months up to 1 year
measure: Complications
time frame: 48 hours
description: 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.
arm group label: ROSE with guide sheath
arm group type: Experimental
description: Patients will undergo pEBUS with a regular size bronchoscope using the guide sheath technique and presence of ROSE
arm group label: ROSE without guide sheath
arm group type: Experimental
description: Patients will undergo pEBUS with a slim bronchoscope combined with a 1.7mm radial probe but no guide sheath and the presence of ROSE.
arm group label: Guide sheath without ROSE
arm group type: Experimental
description: Patients will undergo pEBUS with a regular size bronchoscope using the guide sheath technique but without ROSE.
arm group label: No guide sheath without ROSE
arm group type: Experimental
description: 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.
intervention type: Procedure
intervention name: Rapid on-site evaluation (ROSE)
description: Pathologist on site for direct evaluation of specimen adequacy
arm group label: ROSE with guide sheath
arm group label: ROSE without guide sheath
intervention type: Procedure
intervention name: Slim bronchoscope without a guide sheath
description: 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.
arm group label: No guide sheath without ROSE
arm group label: ROSE without guide sheath
other name: Ultrathin bronchoscope with pEBUS
intervention type: Procedure
intervention name: Standard pEBUS with guide sheath
description: Using a flexible bronchoscope with minimal outer diameter of 4.2mm.
arm group label: Guide sheath without ROSE
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alain Tremblay, MDCM
role: Principal Investigator
affiliation: University of Calgary
facility: 
facility: 
country: Canada
responsible party type: Sponsor
sharing ipd: Yes
ipd 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 info type: Study Protocol
ipd time frame: 9 to 36 months following article publication
ipd access criteria: Shared with researchers who will provide a methodologically sound proposal.