xml: <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/NCT06019052</url>
    </required_header>
    <id_info>
      <org_study_id>TB051</org_study_id>
      <nct_id>NCT06019052</nct_id>
    </id_info>
    <brief_title>Evaluating Next Generation LAM Assays and Molecular Diagnostics (POC and Near POC) for the Diagnosis of TB Among People With Presumptive TB: a Prospective Multicentre Diagnostic Accuracy Study</brief_title>
    <acronym>DriveDx4TB</acronym>
    <official_title>Testing New Diagnostic Technology Classes for TB (DriveDx4TB)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Foundation for Innovative New Diagnostics, Switzerland</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Foundation for Innovative New Diagnostics, Switzerland</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>
        This prospective multicentre study is planned to evaluate the next generation LAM assays and&#xD;
        molecular diagnostics (POC and near POC) among people with presumptive Tuberculosis. The&#xD;
        DriveDx4TB study aims to generate evidence needed to accelerate the introduction of three new&#xD;
        classes of TB diagnostics, complemented by alternative sampling for use at primary healthcare&#xD;
        and community settings. To this end, the study will leverage the accelerated innovation&#xD;
        spurred by the COVID-19 pandemic, particularly the rapid development of swab-based sampling&#xD;
        and molecular diagnostic (MDx) platforms.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Tuberculosis (TB) remains a major global health problem owing to high rates of morbidity and&#xD;
        mortality; the 2022 Global TB Report estimates that approximately 10.6 million individuals&#xD;
        fell ill with TB in 2021, however on account of existing programme inefficiencies and&#xD;
        compounded by the effects of COVID-19, 4.1 million people with TB went undiagnosed. Access to&#xD;
        diagnostics remains a significant barrier to TB care, further exacerbated by COVID-19; the&#xD;
        consequence of delayed diagnoses and subsequent treatment has resulted in increased TB deaths&#xD;
        (1.4M deaths in 2021 - levels last seen in 2017). In addition, a reliance on sputum-based&#xD;
        testing has limited case detection efforts, particularly among individuals with&#xD;
        paucibacillary disease (e.g., people living with HIV [PLHIV] and children) and those&#xD;
        investigated earlier in their TB disease progression, where sputum production is inherently&#xD;
        difficult. New fit-for-purpose diagnostics are thus urgently needed to recover lost ground&#xD;
        and to bring testing closer to patients and address current sampling limitations.&#xD;
  &#xD;
        The DriveDx4TB project aims to generate evidence needed to accelerate the introduction of&#xD;
        three new classes of TB diagnostics, complemented by alternative sampling for use at primary&#xD;
        healthcare and community settings. To this end, the study will leverage the accelerated&#xD;
        innovation spurred by the COVID-19 pandemic, particularly the rapid development of swab-based&#xD;
        sampling and molecular diagnostic (MDx) platforms.&#xD;
  &#xD;
        The project will independently evaluate three technology classes:&#xD;
  &#xD;
          1. 3rd Generation urine LAM&#xD;
  &#xD;
          2. Point-of-care (POC) MDx using tongue swabs&#xD;
  &#xD;
          3. Near POC MDx using tongue swabs or sputum&#xD;
  &#xD;
        The data gathered from this study will support in-country decision-making for the uptake of&#xD;
        new TB diagnostics, and will form part of evidence reviewed by the WHO for policy development&#xD;
        or prequalification (PQ) processes.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">February 2024</start_date>
    <completion_date type="Anticipated">November 2025</completion_date>
    <primary_completion_date type="Anticipated">August 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Other</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>1.1</measure>
      <time_frame>February 2024 to August 2025</time_frame>
      <description>Determination of the diagnostic accuracy of POC index tests using urine samples for TB detection among adults with presumptive pulmonary TB using as reference standards MRS, eMRS, and CRS. Point estimates (with 95% confidence intervals) of sensitivity, specificity, balanced accuracy, diagnostic odds ratio (DOR), positive and negative predictive values (PPV and NPV) for POC index tests using the defined MRS, eMRS and CRS as reference standards. Point estimates of sensitivity and specificity will be calculated based on the definitions reported in protocol, with 95% confidence intervals calculated using Wilson's score method.&#xD;
  The efficacy analyses will be performed on the PP population. Additional subgroup analyses of the primary endpoints will be performed as per SAP.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>1.2</measure>
      <time_frame>February 2024 to August 2025</time_frame>
      <description>Determination of the diagnostic accuracy of near POC MDx index tests using tongue swabs for TB detection among adults with presumptive pulmonary TB using as reference standards MRS, eMRS and CRS. Point estimates (with 95% confidence intervals) of sensitivity, specificity, balanced accuracy, DOR, PPV and NPV for near POC MDx index tests, using the defined MRS, eMRS and CRS as reference standards. Point estimates of sensitivity and specificity will be calculated based on the definitions reported in protocol with 95% confidence intervals calculated using Wilson's score method.&#xD;
  The efficacy analyses will be performed on the PP population. Additional subgroup analyses of the primary endpoints will be performed as per SAP.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>1.3</measure>
      <time_frame>February 2024 to August 2025</time_frame>
      <description>Determination of the diagnostic accuracy of low complexity NAAT index tests using tongue swabs or sputum for TB detection among adults with presumptive pulmonary TB using as reference standards MRS, eMRS and CRS.Point estimates (with 95% confidence intervals) of sensitivity, specificity, balanced accuracy, DOR, PPV and NPV for low complexity index tests, using the defined MRS, eMRS and CRS as reference standards.Point estimates of sensitivity and specificity will be calculated based on the definitions reported in protocol with 95% confidence intervals calculated using Wilson's score method.&#xD;
  The efficacy analyses will be performed on the PP population. Additional subgroup analyses of the primary endpoints will be performed as per SAP.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>2.1</measure>
      <time_frame>February 2024 to August 2025</time_frame>
      <description>Comparison of the diagnostic accuracy between index tests and a comparator test or combinations belonging to the same technology class (POC, near POC MDx or low complexity NAAT), for TB detection among adults with presumptive pulmonary TB. Difference between the point estimates (with 95% confidence intervals) of sensitivity and specificity for each index test and its relative comparator test, using MRS, eMRS and CRS as reference standards. Point estimates of sensitivity and specificity will be calculated based on the definitions reported in protocol with 95% confidence intervals calculated using Wilson's score method.&#xD;
  The efficacy analyses will be performed on the PP population. Additional subgroup analyses of the primary endpoints will be performed as per SAP.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>2.2</measure>
      <time_frame>February 2024 to August 2025</time_frame>
      <description>Determination of the diagnostic accuracy of POC index tests using urine samples, of near POC MDx index tests using tongues swabs, and of near POC MDx index tests using tongue swabs or sputum for TB detection among adults with presumptive pulmonary TB and HIV infection using MRS, eMRS and CRS. Point estimates (with 95% confidence intervals) of sensitivity, specificity, balanced accuracy, DOR, PPV and NPV for POC index tests using urine samples, near POC MDx index tests using tongues swabs, and low complexity NAAT index tests using tongue swabs or sputum, in the TB and HIV co-infection subgroup using MRS, eMRS and CRS as reference standards.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>2.3</measure>
      <time_frame>February 2024 to August 2025</time_frame>
      <description>Evaluation of the usability of POC, of near POC MDx and of low complexity NAAT index tests in a real-world setting. Usability of each index test (3rd generation LAM, near POC MDx and low complexity NAAT) measured by the operators' ability to understand the test instructions, workflow and results interpretation.</description>
    </secondary_outcome>
    <enrollment type="Anticipated">1890</enrollment>
    <condition>Tuberculosis</condition>
    <eligibility>
      <study_pop>
        <textblock>
          Approximately 1800 Adult (≥18 years), with presumptive pulmonary TB i.e., self-reporting&#xD;
          cough ≥2 weeks and ≥1 other symptom typical of pulmonary TB* will be enrolled in the study.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adult (≥18 years), with presumptive pulmonary TB i.e., self-reporting cough ≥2 weeks&#xD;
               and ≥1 other symptom typical of pulmonary TB*&#xD;
  &#xD;
            -  Willing to provide written informed consent&#xD;
  &#xD;
            -  Willing to provide sputum, and other samples (tongue swabs, urine)&#xD;
  &#xD;
            -  Willingness to have a telephonic follow-up call 2-3 months post-enrolment&#xD;
  &#xD;
            -  Documented HIV status and CD4 count within last 6 months, or if unavailable, then&#xD;
               willing to undergo testing&#xD;
  &#xD;
            -  fever, night sweats or unintended weight-loss&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Participants currently on anti-TB treatment *&#xD;
  &#xD;
            -  Any anti-TB treatment or antibiotics not specifically used for TB treatment, but which&#xD;
               have anti-TB activity, e.g., fluoroquinolones given for respiratory tract infection&#xD;
               within 60 days prior to enrolment&#xD;
  &#xD;
            -  Any tuberculosis preventive therapy (TPT) within 6 months prior to enrolment&#xD;
  &#xD;
            -  Participants who have conditions or circumstances that preclude their participation,&#xD;
               based on the judgement of the site investigator&#xD;
  &#xD;
            -  Unable to produce at least 3ml of sputum * Participants starting anti-TB treatment at&#xD;
               the time of enrolment will not be excluded from the study provided that all study&#xD;
               specimens are collected before starting the 3rd dose of treatment.&#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_contact>
      <last_name>Pamela Nabeta, Medical Doctor</last_name>
      <phone>+41 22 710 27 87</phone>
      <email>pamela.nabeta@finddx.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Charu Paliwal, Master in Biotechnology</last_name>
      <phone>09560003368</phone>
      <email>charu.paliwal@finddx.org</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>TB</keyword>
    <keyword>Diagnostics</keyword>
    <keyword>HIV</keyword>
    <keyword>Diagnostic accuracy study</keyword>
    <keyword>Alternative samples</keyword>
    <keyword>Point of care (POC)</keyword>
    <keyword>Near POC</keyword>
    <keyword>Molecular diagnostic (MDx) platforms</keyword>
    <keyword>Urine LAM</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tuberculosis</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06019052
  org study id: TB051
  nct id: NCT06019052
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This prospective multicentre study is planned to evaluate the next generation LAM assays and
        molecular diagnostics (POC and near POC) among people with presumptive Tuberculosis. The
        DriveDx4TB study aims to generate evidence needed to accelerate the introduction of three new
        classes of TB diagnostics, complemented by alternative sampling for use at primary healthcare
        and community settings. To this end, the study will leverage the accelerated innovation
        spurred by the COVID-19 pandemic, particularly the rapid development of swab-based sampling
        and molecular diagnostic (MDx) platforms.
  Tuberculosis (TB) remains a major global health problem owing to high rates of morbidity and
        mortality; the 2022 Global TB Report estimates that approximately 10.6 million individuals
        fell ill with TB in 2021, however on account of existing programme inefficiencies and
        compounded by the effects of COVID-19, 4.1 million people with TB went undiagnosed. Access to
        diagnostics remains a significant barrier to TB care, further exacerbated by COVID-19; the
        consequence of delayed diagnoses and subsequent treatment has resulted in increased TB deaths
        (1.4M deaths in 2021 - levels last seen in 2017). In addition, a reliance on sputum-based
        testing has limited case detection efforts, particularly among individuals with
        paucibacillary disease (e.g., people living with HIV [PLHIV] and children) and those
        investigated earlier in their TB disease progression, where sputum production is inherently
        difficult. New fit-for-purpose diagnostics are thus urgently needed to recover lost ground
        and to bring testing closer to patients and address current sampling limitations.
  
        The DriveDx4TB project aims to generate evidence needed to accelerate the introduction of
        three new classes of TB diagnostics, complemented by alternative sampling for use at primary
        healthcare and community settings. To this end, the study will leverage the accelerated
        innovation spurred by the COVID-19 pandemic, particularly the rapid development of swab-based
        sampling and molecular diagnostic (MDx) platforms.
  
        The project will independently evaluate three technology classes:
  
          1. 3rd Generation urine LAM
  
          2. Point-of-care (POC) MDx using tongue swabs
  
          3. Near POC MDx using tongue swabs or sputum
  
        The data gathered from this study will support in-country decision-making for the uptake of
        new TB diagnostics, and will form part of evidence reviewed by the WHO for policy development
        or prequalification (PQ) processes.
  observational model: Other
  time perspective: Prospective
  measure: 1.1
  time frame: February 2024 to August 2025
  description: Determination of the diagnostic accuracy of POC index tests using urine samples for TB detection among adults with presumptive pulmonary TB using as reference standards MRS, eMRS, and CRS. Point estimates (with 95% confidence intervals) of sensitivity, specificity, balanced accuracy, diagnostic odds ratio (DOR), positive and negative predictive values (PPV and NPV) for POC index tests using the defined MRS, eMRS and CRS as reference standards. Point estimates of sensitivity and specificity will be calculated based on the definitions reported in protocol, with 95% confidence intervals calculated using Wilson's score method.
  The efficacy analyses will be performed on the PP population. Additional subgroup analyses of the primary endpoints will be performed as per SAP.
  measure: 1.2
  time frame: February 2024 to August 2025
  description: Determination of the diagnostic accuracy of near POC MDx index tests using tongue swabs for TB detection among adults with presumptive pulmonary TB using as reference standards MRS, eMRS and CRS. Point estimates (with 95% confidence intervals) of sensitivity, specificity, balanced accuracy, DOR, PPV and NPV for near POC MDx index tests, using the defined MRS, eMRS and CRS as reference standards. Point estimates of sensitivity and specificity will be calculated based on the definitions reported in protocol with 95% confidence intervals calculated using Wilson's score method.
  The efficacy analyses will be performed on the PP population. Additional subgroup analyses of the primary endpoints will be performed as per SAP.
  measure: 1.3
  time frame: February 2024 to August 2025
  description: Determination of the diagnostic accuracy of low complexity NAAT index tests using tongue swabs or sputum for TB detection among adults with presumptive pulmonary TB using as reference standards MRS, eMRS and CRS.Point estimates (with 95% confidence intervals) of sensitivity, specificity, balanced accuracy, DOR, PPV and NPV for low complexity index tests, using the defined MRS, eMRS and CRS as reference standards.Point estimates of sensitivity and specificity will be calculated based on the definitions reported in protocol with 95% confidence intervals calculated using Wilson's score method.
  The efficacy analyses will be performed on the PP population. Additional subgroup analyses of the primary endpoints will be performed as per SAP.
  measure: 2.1
  time frame: February 2024 to August 2025
  description: Comparison of the diagnostic accuracy between index tests and a comparator test or combinations belonging to the same technology class (POC, near POC MDx or low complexity NAAT), for TB detection among adults with presumptive pulmonary TB. Difference between the point estimates (with 95% confidence intervals) of sensitivity and specificity for each index test and its relative comparator test, using MRS, eMRS and CRS as reference standards. Point estimates of sensitivity and specificity will be calculated based on the definitions reported in protocol with 95% confidence intervals calculated using Wilson's score method.
  The efficacy analyses will be performed on the PP population. Additional subgroup analyses of the primary endpoints will be performed as per SAP.
  measure: 2.2
  time frame: February 2024 to August 2025
  description: Determination of the diagnostic accuracy of POC index tests using urine samples, of near POC MDx index tests using tongues swabs, and of near POC MDx index tests using tongue swabs or sputum for TB detection among adults with presumptive pulmonary TB and HIV infection using MRS, eMRS and CRS. Point estimates (with 95% confidence intervals) of sensitivity, specificity, balanced accuracy, DOR, PPV and NPV for POC index tests using urine samples, near POC MDx index tests using tongues swabs, and low complexity NAAT index tests using tongue swabs or sputum, in the TB and HIV co-infection subgroup using MRS, eMRS and CRS as reference standards.
  measure: 2.3
  time frame: February 2024 to August 2025
  description: Evaluation of the usability of POC, of near POC MDx and of low complexity NAAT index tests in a real-world setting. Usability of each index test (3rd generation LAM, near POC MDx and low complexity NAAT) measured by the operators' ability to understand the test instructions, workflow and results interpretation.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Pamela Nabeta, Medical Doctor
  phone: +41 22 710 27 87
  email: pamela.nabeta@finddx.org
  last name: Charu Paliwal, Master in Biotechnology
  phone: 09560003368
  email: charu.paliwal@finddx.org
  responsible party type: Sponsor
  mesh term: Tuberculosis