<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/NCT04407325</url>
  </required_header>
  <id_info>
    <org_study_id>823890-EUSAT-RCS</org_study_id>
    <nct_id>NCT04407325</nct_id>
  </id_info>
  <brief_title>Tuberculosis Screening in Paraguayan Prisons</brief_title>
  <acronym>Prinose</acronym>
  <official_title>Tuberculosis Screening With AeoNose and CAD4TB in Paraguayan Prisons</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Union</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Instituto de Saude Publica da Universidade do Porto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>VHIR</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Laboratorio central de salud publica, Paraguay</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Instituto Nacional de Enfermedades Respiratorias y del Ambiente Juan Max Boetner</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National TB program Paraguay</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>IICS Paraguay</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Two diagnostic tools for TB screening in high risk groups need additional assessment: the&#xD;
      AeoNose™, an 'electronic nose device' for breath sampling, and digital chest X-ray (CXR) with&#xD;
      computer aided detection with CAD4TB® software. This study will systematically screen&#xD;
      prisoners and its' employees for TB, test the diagnostic performance of AeoNose™ and CAD4TB&#xD;
      (both individually and together) as a TB screening tool and and establish Mycobacterium&#xD;
      tuberculosis epidemiology in Paraguayan prisons.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of the World Health Organization (WHO) &quot;End TB Strategy&quot; is to end the global&#xD;
      pandemic by 2035. To be able to succeed, better point-of-care (POC) tests are urgently needed&#xD;
      to improve screening of high-risk populations. Prisons are recognized worldwide as high risk&#xD;
      environments for the concentration, amplification and transmission of TB among prisoners and&#xD;
      their communities outside. Paraguayan penal institutions are known to have very high&#xD;
      incidence rates of active TB (3000-5000/100.000, according to Paraguayan Ministry of&#xD;
      Justice). Two diagnostic tools for TB screening in high risk groups will be evaluated: the&#xD;
      AeoNose™, an 'electronic nose device' for breath sampling, and digital chest X-ray (CXR) with&#xD;
      computer aided detection with CAD4TB® software. This study will systematically screen&#xD;
      prisoners and its' employees for TB, test the diagnostic performance of AeoNose™ and CAD4TB®&#xD;
      and assess prison Mycobacterium tuberculosis epidemiology through several objectives:&#xD;
      Objective: 1. Assessment of the sensitivity and specificity of the AeoNose™ and its utility&#xD;
      for mass TB screening in high incidence settings. 2. Evaluation of the feasibility and&#xD;
      utility of CAD4TB® digital CXR as a mass screening tool for TB. 3. Identification of factors&#xD;
      that affect diagnostic accuracy of AeoNose™ and CAD4TB®. 4. Assessment of TB epidemiology in&#xD;
      Paraguayan prisons and identification of mycobacterial strains.&#xD;
&#xD;
      Study design: Diagnostic cohort study. Study population: Detainees (PPL) of Paraguayan penal&#xD;
      institutions as well as their employees. Nature and extent of the burden and risks associated&#xD;
      with participation, benefit and group relatedness.&#xD;
&#xD;
      Individual burden: all participants will perform one visit with a medical doctor for medical&#xD;
      history, physical exam, digital X-ray (with CAD4TB®) and AeoNose sampling. Participants will&#xD;
      be offered voluntary HIV testing and counseling. In case of presumptive TB (estimated 20-30%&#xD;
      of participants) two sputum samples will be taken, either spontaneous or saline-induced. One&#xD;
      sample is tested with GeneXpert and the other with liquid mycobacterial culture. Cases of&#xD;
      presumptive TB with both negative GeneXpert® and culture results will be followed-up after&#xD;
      three and six months for repeat testing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 18, 2021</start_date>
  <completion_date type="Anticipated">December 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>outcomes of individual smell prints and digital ChestXrays will be compared with sputum sampling for GenXpert and Mycobacterial culture</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Volatile organic compound signal as measured with the AeoNose™</measure>
    <time_frame>Baseline/ change from baseline at 3 and 6 months</time_frame>
    <description>The exhaled breath 'smell print' of each participant will be compared over time at baseline, 3 months and 6 months with sputum microbiology results and digital Chest Xray to establish sensitivity and specificity of electronic nose signal to diagnose Tuberculosis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tuberculosis probablity score using Computed Automated detection software CAD4TB® on chest Xrays</measure>
    <time_frame>Baseline/ change from baseline at 3 and 6 months</time_frame>
    <description>Ranges from 0 to 100, where 0 would mean the lowest probability of having Tuberculosis and 100 would be the highest probability of having Tuberculosis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Positive mycobacterial sputum test</measure>
    <time_frame>Baseline/ change from baseline at 3 and 6 months</time_frame>
    <description>positive GenXpert test and/or mycobacterial cultures are used to establish Tuberculosis diagnosis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of predictive value of volatile organic compound signal with Tuberculosis Probability Score</measure>
    <time_frame>Baseline/ change from baseline at 3 and 6 months</time_frame>
    <description>comparison of correct positive predictions for active TB, with AeoNose (positive/ negative test result) and Cad4TB software from chest Xrays providing probability scores from 0-100 points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>added value of the use of AeoNose and Cad4TB as a TB screening algorithm in vulnerable populations</measure>
    <time_frame>Baseline/ change from baseline at 3 and 6 months</time_frame>
    <description>evaluation of the combined use of both AeoNose and Cad4TB probability score to predict active TB</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">5000</enrollment>
  <condition>Volatile Organic Compounds</condition>
  <condition>Radiography</condition>
  <arm_group>
    <arm_group_label>AeoNose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>the AeoNose will be compared with digital ChestXray and the conventional methods of establishing TB diagnosis</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>electronic nose device</intervention_name>
    <description>electronic nose device will be tested as a triage instrument for tuberculosis in a high risk population</description>
    <arm_group_label>AeoNose</arm_group_label>
    <other_name>(AeoNose, The eNose Company, the Netherlands)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>dig chest Xray with automated readings</intervention_name>
    <description>software for tuberculosis detection on digital Chest Xray providing a probability score from 0-100</description>
    <arm_group_label>AeoNose</arm_group_label>
    <other_name>CAD4TB computed automated detection software</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All persons, either being a prisoner or employee, of the involved penal institutions&#xD;
             after providing informed consent, including those with known active TB disease and/or&#xD;
             currently on TB treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A potential participant who meets any of the following criteria will be excluded from&#xD;
             participation in this study:&#xD;
&#xD;
               1. Unable to exhale breath through the AeoNose™ during five minutes due to&#xD;
                  respiratory insufficiency&#xD;
&#xD;
               2. Unable to stand in an upright position for the CXR&#xD;
&#xD;
               3. Unable to communicate and comply with the instructions of the study team&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cecile Magis-Escurra, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Luis Gomez Pacielo, MD</last_name>
    <phone>+595961889657</phone>
    <email>luis.gomez@RadboudUMC.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>Buen Pastor</name>
      <address>
        <city>Asuncion</city>
        <state>Central</state>
        <country>Paraguay</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Claudia Pinanez, MD</last_name>
      <email>claupinanez@hotmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>UPI</name>
      <address>
        <city>Asuncion</city>
        <state>Central</state>
        <country>Paraguay</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location_countries>
    <country>Paraguay</country>
  </location_countries>
  <link>
    <url>https://www.eusattb.net/</url>
    <description>EUSAT-RCS TB research consortium</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>April 23, 2020</study_first_submitted>
  <study_first_submitted_qc>May 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>March 30, 2023</last_update_submitted>
  <last_update_submitted_qc>March 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tuberculosis</keyword>
  <keyword>vulnerable populations</keyword>
  <keyword>screening algorithms</keyword>
  <keyword>cost effectiveness</keyword>
  <keyword>neural networks</keyword>
  <keyword>artificial intelligence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 12, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT04407325/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT04407325/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04407325
org study id: 823890-EUSAT-RCS
nct id: NCT04407325
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Two diagnostic tools for TB screening in high risk groups need additional assessment: the
      AeoNose™, an 'electronic nose device' for breath sampling, and digital chest X-ray (CXR) with
      computer aided detection with CAD4TB® software. This study will systematically screen
      prisoners and its' employees for TB, test the diagnostic performance of AeoNose™ and CAD4TB
      (both individually and together) as a TB screening tool and and establish Mycobacterium
      tuberculosis epidemiology in Paraguayan prisons.
The aim of the World Health Organization (WHO) "End TB Strategy" is to end the global
      pandemic by 2035. To be able to succeed, better point-of-care (POC) tests are urgently needed
      to improve screening of high-risk populations. Prisons are recognized worldwide as high risk
      environments for the concentration, amplification and transmission of TB among prisoners and
      their communities outside. Paraguayan penal institutions are known to have very high
      incidence rates of active TB (3000-5000/100.000, according to Paraguayan Ministry of
      Justice). Two diagnostic tools for TB screening in high risk groups will be evaluated: the
      AeoNose™, an 'electronic nose device' for breath sampling, and digital chest X-ray (CXR) with
      computer aided detection with CAD4TB® software. This study will systematically screen
      prisoners and its' employees for TB, test the diagnostic performance of AeoNose™ and CAD4TB®
      and assess prison Mycobacterium tuberculosis epidemiology through several objectives:
      Objective: 1. Assessment of the sensitivity and specificity of the AeoNose™ and its utility
      for mass TB screening in high incidence settings. 2. Evaluation of the feasibility and
      utility of CAD4TB® digital CXR as a mass screening tool for TB. 3. Identification of factors
      that affect diagnostic accuracy of AeoNose™ and CAD4TB®. 4. Assessment of TB epidemiology in
      Paraguayan prisons and identification of mycobacterial strains.

      Study design: Diagnostic cohort study. Study population: Detainees (PPL) of Paraguayan penal
      institutions as well as their employees. Nature and extent of the burden and risks associated
      with participation, benefit and group relatedness.

      Individual burden: all participants will perform one visit with a medical doctor for medical
      history, physical exam, digital X-ray (with CAD4TB®) and AeoNose sampling. Participants will
      be offered voluntary HIV testing and counseling. In case of presumptive TB (estimated 20-30%
      of participants) two sputum samples will be taken, either spontaneous or saline-induced. One
      sample is tested with GeneXpert and the other with liquid mycobacterial culture. Cases of
      presumptive TB with both negative GeneXpert® and culture results will be followed-up after
      three and six months for repeat testing.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: outcomes of individual smell prints and digital ChestXrays will be compared with sputum sampling for GenXpert and Mycobacterial culture
primary purpose: Diagnostic
masking: None (Open Label)
measure: Volatile organic compound signal as measured with the AeoNose™
time frame: Baseline/ change from baseline at 3 and 6 months
description: The exhaled breath 'smell print' of each participant will be compared over time at baseline, 3 months and 6 months with sputum microbiology results and digital Chest Xray to establish sensitivity and specificity of electronic nose signal to diagnose Tuberculosis
measure: Tuberculosis probablity score using Computed Automated detection software CAD4TB® on chest Xrays
time frame: Baseline/ change from baseline at 3 and 6 months
description: Ranges from 0 to 100, where 0 would mean the lowest probability of having Tuberculosis and 100 would be the highest probability of having Tuberculosis.
measure: Positive mycobacterial sputum test
time frame: Baseline/ change from baseline at 3 and 6 months
description: positive GenXpert test and/or mycobacterial cultures are used to establish Tuberculosis diagnosis
measure: Comparison of predictive value of volatile organic compound signal with Tuberculosis Probability Score
time frame: Baseline/ change from baseline at 3 and 6 months
description: comparison of correct positive predictions for active TB, with AeoNose (positive/ negative test result) and Cad4TB software from chest Xrays providing probability scores from 0-100 points
measure: added value of the use of AeoNose and Cad4TB as a TB screening algorithm in vulnerable populations
time frame: Baseline/ change from baseline at 3 and 6 months
description: evaluation of the combined use of both AeoNose and Cad4TB probability score to predict active TB
arm group label: AeoNose
arm group type: Experimental
description: the AeoNose will be compared with digital ChestXray and the conventional methods of establishing TB diagnosis
intervention type: Device
intervention name: electronic nose device
description: electronic nose device will be tested as a triage instrument for tuberculosis in a high risk population
arm group label: AeoNose
other name: (AeoNose, The eNose Company, the Netherlands)
intervention type: Device
intervention name: dig chest Xray with automated readings
description: software for tuberculosis detection on digital Chest Xray providing a probability score from 0-100
arm group label: AeoNose
other name: CAD4TB computed automated detection software
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Cecile Magis-Escurra, MD,PhD
role: Principal Investigator
affiliation: Radboud University Medical Center
last name: Luis Gomez Pacielo, MD
phone: +595961889657
email: luis.gomez@RadboudUMC.nl
facility: 
status: Recruiting
contact: 
facility: 
status: Completed
country: Paraguay
url: https://www.eusattb.net/
description: EUSAT-RCS TB research consortium
responsible party type: Sponsor
mesh term: Tuberculosis
sharing ipd: No
provided document: 
provided document: 