<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/NCT03274609</url>
  </required_header>
  <id_info>
    <org_study_id>NL63109.091.17</org_study_id>
    <nct_id>NCT03274609</nct_id>
  </id_info>
  <brief_title>CT-controlled Advanced Navigation Techniques for Transbronchial Pulmonary Lesion Access; Evaluation of Augmented Fluoroscopy Bronchoscopic Navigation Based Diagnostic Yield</brief_title>
  <acronym>CONTROL-A</acronym>
  <official_title>CT-controlled Advanced Navigation Techniques for Transbronchial Pulmonary Lesion Access; Evaluation of Augmented Fluoroscopy Bronchoscopic Navigation Based Diagnostic Yield</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this exploratory adaptive clinical trial the investigators will examine the diagnostic&#xD;
      yield of a combination of commercially available imaging and navigation techniques for&#xD;
      reaching peripheral lung lesions. The two investigated techniques will herein be the rEBUS&#xD;
      imaging modality combined with augmented fluoroscopy based virtual bronchoscopy navigation.&#xD;
      Confirmation of reaching the lung lesion will be by means of CT (fluoroscopic) imaging. Rapid&#xD;
      On-Site Evaluation (ROSE) of cytopathology will be used for obtaing a per-procedural outcome&#xD;
      on tissue biopsy representativeness. The study will replace the current conventional standard&#xD;
      TBB procedure (fluoroscopy and rEBUS guided bronchoscopy) in the endoscopy suite. Consecutive&#xD;
      patients will be included on the MITeC hybrid operating room (needed to monitor patient&#xD;
      safety and CT availability). All data will be prospectively collected. In case tissue biopsy&#xD;
      is found to be malignant or benign, it will be termed representative. In case tissue biopsy&#xD;
      is found to be non-representative (=blood, anatomical lung tissue, unreachable), conventional&#xD;
      follow-up of CT guided TTNA, follow-up monitoring and/or surgical biopsy will serve as golden&#xD;
      standard for obtaining tissue diagnosis. For verification of reaching the target lesion,&#xD;
      another study parameter of interest, (cb)CT imaging will be performed for verification that&#xD;
      instruments are within the nodule (per-procedurally available).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lung cancer is one of the leading most frequent types of cancer and is the most lethal&#xD;
      malignancy in the Netherlands. Mortality is high due to its advanced stage disease at&#xD;
      diagnosis. To improve survival current guidelines are moving towards CT-screening of the high&#xD;
      risk population. These CT-scans detect numerous nodules and rapidly increase the demand for&#xD;
      minimal invasive accurate and safe diagnostic procedures.&#xD;
&#xD;
      The historically available and current first diagnostic procedure in the work-up of PPLs is&#xD;
      fluoroscopy guided Trans Bronchial Biopsy (TBB) despite its low pooled yield of 31.1%. When&#xD;
      the above transbronchial technique does not provide an unambiguous outcome, an additional and&#xD;
      more invasive diagnostic work-up remains indicated. To exclude the possibility of missing&#xD;
      malignancies, trans thoracic needle aspiration is first indicated. If deemed inaccessible,&#xD;
      surgical biopsy may be alternatively indicated depending on patient risk of malignancy.&#xD;
      Ideally, a transbronchial approach having high diagnostic accuracy would overcome the need of&#xD;
      this sequential increasingly invasive diagnostic and consecutive treatment approach. Newer&#xD;
      pilot studies now hypothesize that combining multiple new endobronchial modalities might&#xD;
      provide a solution in preventing more invasive additional diagnostic staging, reporting&#xD;
      diagnostic yields exceeding 70%. When an accurate and certain transbronchial diagnosis by&#xD;
      combining multiple techniques can indeed be provided. We will study a combination of new&#xD;
      advanced modalities for diagnosis of peripheral nodules endobronchially. The aim of this&#xD;
      study is to determine diagnostic yield, cost-effectiveness, safety, and, to collect data for&#xD;
      developing diagnostic algorithms to further cost-effectively increase yield, reduce&#xD;
      complication rate and determine a future platform for clinical implementation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 21, 2017</start_date>
  <completion_date type="Actual">November 1, 2019</completion_date>
  <primary_completion_date type="Actual">January 1, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>number of patients with an adequate diagnosis (=diagnostic yield)</measure>
    <time_frame>0-12 months</time_frame>
    <description>diagnosis will consist of benign, malign or non-representative (=blood, anatomical lung tissue, unreachable)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>number of patients with (S)AE's related to the procedure</measure>
    <time_frame>0-12 months</time_frame>
    <description>minor bleeding and pneumothoraces are reported</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cost-effectiveness</measure>
    <time_frame>0-12 months</time_frame>
    <description>the study procedures will be compared against the conventional diagnostic TBB work-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>radiation exposure</measure>
    <time_frame>0-12 months</time_frame>
    <description>compared against conventional TBB and consecutive TTNA procedure</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">47</enrollment>
  <condition>Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Suspected lung cancer</arm_group_label>
    <description>Patients referred as part of a first diagnostic evaluation of newly detected pulmonary lesion(s) or when an indication for an invasive diagnostic procedure is found during follow-up of earlier detected pulmonary lesion.&#xD;
Patients identified during per protocol CT imaging follow-up of known lesions when growth of the lesion is found and an indication for biopsy is determined by the treating physician and/or multidisciplinary board.&#xD;
Patients identified when referred for surgical biopsy in case of nodule location inaccessible for CT-guided TTNA.&#xD;
These will be subjected to a combined approach of modalities with the main intervention being augmented fluoroscopy guided virtual navigation.)</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Augmented fluoroscopy</intervention_name>
    <description>Augmented fluoroscopy based virtual navigation combined with use of radial EBUS probe and Rapid On Site Evaluation of Histology for diagnosis of peripheral pulmonary nodules.Controlled by cone beam CT.</description>
    <arm_group_label>Suspected lung cancer</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      biopsies of peripheral nodules&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will consist of patients diagnosed with peripheral pulmonary lesion(s)&#xD;
        and an indication to obtain a tissue sample(s) following current conventional procedure&#xD;
        work-up. In all patients, preprocedural imaging (including CT and/or PET-CT findings)&#xD;
        following conventional work-up is available. Case selection for the clinical indication to&#xD;
        perform a peripheral pulmonary biopsy (non-surgical and/or surgical) will follow current&#xD;
        local clinical practice, multidisciplinary tumor board decisions and is in accordance to&#xD;
        the latest British Thoracic Society guidelines (British Thoracic Society Pulmonary Nodule&#xD;
        Guideline Development Group, 2015). Patients are eligible after informed consent is&#xD;
        obtained and when direct contra-indications for the endobronchial procedure are absent.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        In order to be eligible to participate in this study, a subject must meet all of the&#xD;
        following criteria:&#xD;
&#xD;
          -  ASA physical status 1-3.&#xD;
&#xD;
          -  Age 18 years or older.&#xD;
&#xD;
          -  A pulmonary lesion (i.e. a focal, rounded opacity mostly surrounded by aerated lung or&#xD;
             a ground glass opacity or part- or sub-solid lesion) with an indication for diagnostic&#xD;
             evaluation following current clinical guidelines and/or as decided by&#xD;
             multi-disciplinary team consultation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A potential subject who meets any of the following criteria will be excluded from&#xD;
        participation in this study:&#xD;
&#xD;
          -  Bleeding disorders.&#xD;
&#xD;
          -  Less than 18 years old.&#xD;
&#xD;
          -  Contra-indication for temporary interruption of the use of anticoagulant therapy&#xD;
             (acenocoumarol, warfarin, therapeutic dose of low molecular weight heparines,&#xD;
             clopidrogel, analogs, or, NOAC's).&#xD;
&#xD;
          -  Known allergy for lidocaine.&#xD;
&#xD;
          -  Uncontrolled pulmonary hypertension.&#xD;
&#xD;
          -  Recent and/or uncontrolled cardiac disease.&#xD;
&#xD;
          -  Compromised upper airway (e.g. concomitant head and neck cancer or central airway&#xD;
             stenosis for any reason such that endobronchial access is considered unsafe).&#xD;
&#xD;
          -  ASA classification greater than or equal to 4 (unfit for performing non-surgical&#xD;
             biopsy).&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Inability to 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>Linda Garms</last_name>
    <role>Study Chair</role>
    <affiliation>Study coordinator</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Erik van der Heijden, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Pulmonary diseases</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Roel Verhoeven, Msc</last_name>
    <role>Study Chair</role>
    <affiliation>Pulmonary diseases / Radiology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <zip>6525GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>September 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>December 13, 2019</last_update_submitted>
  <last_update_submitted_qc>December 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lung diseases</keyword>
  <keyword>cancer</keyword>
  <keyword>Interventional pulmonology</keyword>
  <keyword>peripheral nodule</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03274609
org study id: NL63109.091.17
nct id: NCT03274609
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
In this exploratory adaptive clinical trial the investigators will examine the diagnostic
      yield of a combination of commercially available imaging and navigation techniques for
      reaching peripheral lung lesions. The two investigated techniques will herein be the rEBUS
      imaging modality combined with augmented fluoroscopy based virtual bronchoscopy navigation.
      Confirmation of reaching the lung lesion will be by means of CT (fluoroscopic) imaging. Rapid
      On-Site Evaluation (ROSE) of cytopathology will be used for obtaing a per-procedural outcome
      on tissue biopsy representativeness. The study will replace the current conventional standard
      TBB procedure (fluoroscopy and rEBUS guided bronchoscopy) in the endoscopy suite. Consecutive
      patients will be included on the MITeC hybrid operating room (needed to monitor patient
      safety and CT availability). All data will be prospectively collected. In case tissue biopsy
      is found to be malignant or benign, it will be termed representative. In case tissue biopsy
      is found to be non-representative (=blood, anatomical lung tissue, unreachable), conventional
      follow-up of CT guided TTNA, follow-up monitoring and/or surgical biopsy will serve as golden
      standard for obtaining tissue diagnosis. For verification of reaching the target lesion,
      another study parameter of interest, (cb)CT imaging will be performed for verification that
      instruments are within the nodule (per-procedurally available).
Lung cancer is one of the leading most frequent types of cancer and is the most lethal
      malignancy in the Netherlands. Mortality is high due to its advanced stage disease at
      diagnosis. To improve survival current guidelines are moving towards CT-screening of the high
      risk population. These CT-scans detect numerous nodules and rapidly increase the demand for
      minimal invasive accurate and safe diagnostic procedures.

      The historically available and current first diagnostic procedure in the work-up of PPLs is
      fluoroscopy guided Trans Bronchial Biopsy (TBB) despite its low pooled yield of 31.1%. When
      the above transbronchial technique does not provide an unambiguous outcome, an additional and
      more invasive diagnostic work-up remains indicated. To exclude the possibility of missing
      malignancies, trans thoracic needle aspiration is first indicated. If deemed inaccessible,
      surgical biopsy may be alternatively indicated depending on patient risk of malignancy.
      Ideally, a transbronchial approach having high diagnostic accuracy would overcome the need of
      this sequential increasingly invasive diagnostic and consecutive treatment approach. Newer
      pilot studies now hypothesize that combining multiple new endobronchial modalities might
      provide a solution in preventing more invasive additional diagnostic staging, reporting
      diagnostic yields exceeding 70%. When an accurate and certain transbronchial diagnosis by
      combining multiple techniques can indeed be provided. We will study a combination of new
      advanced modalities for diagnosis of peripheral nodules endobronchially. The aim of this
      study is to determine diagnostic yield, cost-effectiveness, safety, and, to collect data for
      developing diagnostic algorithms to further cost-effectively increase yield, reduce
      complication rate and determine a future platform for clinical implementation.
observational model: Cohort
time perspective: Prospective
measure: number of patients with an adequate diagnosis (=diagnostic yield)
time frame: 0-12 months
description: diagnosis will consist of benign, malign or non-representative (=blood, anatomical lung tissue, unreachable)
measure: number of patients with (S)AE's related to the procedure
time frame: 0-12 months
description: minor bleeding and pneumothoraces are reported
measure: cost-effectiveness
time frame: 0-12 months
description: the study procedures will be compared against the conventional diagnostic TBB work-up
measure: radiation exposure
time frame: 0-12 months
description: compared against conventional TBB and consecutive TTNA procedure
arm group label: Suspected lung cancer
description: Patients referred as part of a first diagnostic evaluation of newly detected pulmonary lesion(s) or when an indication for an invasive diagnostic procedure is found during follow-up of earlier detected pulmonary lesion.
Patients identified during per protocol CT imaging follow-up of known lesions when growth of the lesion is found and an indication for biopsy is determined by the treating physician and/or multidisciplinary board.
Patients identified when referred for surgical biopsy in case of nodule location inaccessible for CT-guided TTNA.
These will be subjected to a combined approach of modalities with the main intervention being augmented fluoroscopy guided virtual navigation.)
intervention type: Combination Product
intervention name: Augmented fluoroscopy
description: Augmented fluoroscopy based virtual navigation combined with use of radial EBUS probe and Rapid On Site Evaluation of Histology for diagnosis of peripheral pulmonary nodules.Controlled by cone beam CT.
arm group label: Suspected lung cancer
biopsies of peripheral nodules
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Linda Garms
role: Study Chair
affiliation: Study coordinator
last name: Erik van der Heijden, MD PhD
role: Principal Investigator
affiliation: Pulmonary diseases
last name: Roel Verhoeven, Msc
role: Study Chair
affiliation: Pulmonary diseases / Radiology
facility: 
country: Netherlands
responsible party type: Sponsor
sharing ipd: No