<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/NCT04433195</url>
  </required_header>
  <id_info>
    <org_study_id>N202002038</org_study_id>
    <nct_id>NCT04433195</nct_id>
  </id_info>
  <brief_title>Xpert MTB/RIF Test in the Diagnosis of Pulmonary Tuberculosis</brief_title>
  <official_title>Xpert MTB/RIF Test as the Initial Diagnostic Test in the Diagnosis of Pulmonary Tuberculosis: a Pragmatic Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taipei Medical University WanFang Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Buddhist Tzu Chi General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chest Hospital, Ministry of Health and Welfare, Taiwan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chang-Hua Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Taichung Veterans General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Taipei Medical University WanFang Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Currently in Taiwan, most clinicians use sputum smear and culture for the diagnosis of&#xD;
      pulmonary tuberculosis (TB) and apply nucleic acid amplification (NAA) test in a selected&#xD;
      manner. In 2013, the World Health Organization issued conditional recommendation that Xpert&#xD;
      MTB/RIF may be used rather than conventional microscopy and culture as the initial diagnostic&#xD;
      test in all adults suspected of having TB. The newly published Taiwan guidelines for TB&#xD;
      diagnosis and treatment has recommended NAA test, together with smear and culture, as the&#xD;
      initial diagnostic test in individuals suspected of having TB. The investigators conduct a&#xD;
      prospective study to investigate the use of Xpert MTB/RIF as the initial diagnostic test of&#xD;
      pulmonary TB under a pragmatic trial design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study the investigators will respect current practice in the use of NAA in the&#xD;
      diagnosis of pulmonary TB. Clinicians may have ordered NAA as the initial diagnostic test in&#xD;
      adults suspected of having pulmonary TB (group A, Immediate NAA by clinician), and the&#xD;
      investigators will not intervene. For patients who do not have NAA as the initial diagnostic&#xD;
      test, the investigators will use random permuted blocks to randomize these participants into&#xD;
      two groups. One group will have immediate Xpert test (intervention group) as the initial&#xD;
      diagnostic test and another group will continue usual care without immediate Xpert test&#xD;
      (control group).&#xD;
&#xD;
      Group A (Immediate NAA by clinician): NAA as the initial diagnostic test for pulmonary TB&#xD;
      requested by clinicians.&#xD;
&#xD;
      Group B (Immediate NAA as intervention): NAA as the initial diagnostic test for pulmonary TB&#xD;
      not requested by clinicians, but is performed as intervention in this study (intervention&#xD;
      group).&#xD;
&#xD;
      Group C (No immediate NAA): NAA as the initial diagnostic test for pulmonary TB not requested&#xD;
      by clinicians, and is not performed as the initial diagnostic test in this study (control&#xD;
      group). NAA may be ordered at a later point in time by clinicians as an add-on test after&#xD;
      sputum smear microscopy.&#xD;
&#xD;
      The investigators will assess pulmonary TB cases detected in all groups regarding&#xD;
&#xD;
        1. The interval between sputum examinations and initiation of ant-TB treatment.&#xD;
&#xD;
        2. The proportion of culture confirmed pulmonary TB among all pulmonary TB cases notified.&#xD;
&#xD;
        3. The proportion of TB patients who are advised to stop anti-TB treatment before&#xD;
           completion of a treatment course.&#xD;
&#xD;
        4. Outcome of tuberculosis treatment, including patients who die before anti-TB treatment.&#xD;
&#xD;
      Among patients with NAA as the initial diagnostic test (Group A and Group B), the&#xD;
      investigators will investigate&#xD;
&#xD;
        1. Performance (sensitivity, specificity and predictive values) of NAA in the diagnosis of&#xD;
           culture positive pulmonary TB.&#xD;
&#xD;
        2. The incremental yield of the second and third smear in patients who have both NAA test&#xD;
           and smear microscopy as the initial diagnostic test, aiming to determine the&#xD;
           contribution of the second and third smear in the diagnosis of pulmonary TB.&#xD;
&#xD;
        3. The proportion of NAA positive cases who were culture negative.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">October 31, 2021</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>Parallel Assignment</intervention_model>
    <intervention_model_description>pragmatic trial</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>both care providers and participants will be informed of positive results of Xpert MTB/RIF test</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>diagnostic turnaround time</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>The interval between sputum examinations and initiation of ant-TB treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>culture positive pulmonary TB</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>The proportion of culture confirmed pulmonary TB among pulmonary TB cases notified</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change diagnosis</measure>
    <time_frame>12 months after the initiation of anti-tuberculosis treatment</time_frame>
    <description>The proportion of TB patients who are advised to stop anti-TB treatment before completion of a treatment course</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>treatment outcomes</measure>
    <time_frame>12 months after the initiation of anti-tuberculosis treatment</time_frame>
    <description>The proportion of patients who die before anti-TB treatment, who are successfully treated, who died during treatment, who are loss-to-follow-up, who have treatment failure and who are transferred out</description>
  </secondary_outcome>
  <other_outcome>
    <measure>performance of nucleic acid amplification test</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>sensitivity, specificity and predictive values of nucleic acid amplification test in the diagnosis of culture positive pulmonary TB</description>
  </other_outcome>
  <other_outcome>
    <measure>incremental yield</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>The incremental yield of the second and third smear in patients who have both NAA test and smear microscopy as the initial diagnostic test, aiming to determine the contribution of the second and third smear in the diagnosis of pulmonary TB</description>
  </other_outcome>
  <other_outcome>
    <measure>NAA false positive</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>The proportion of nucleic acid amplification test positive cases who were culture negative</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">6900</enrollment>
  <condition>Pulmonary Tuberculosis Confirmation by Culture</condition>
  <arm_group>
    <arm_group_label>Immediate NAA by clinician</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Nucleic acid amplification test requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Immediate NAA as intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nucleic acid amplification test not requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB, but Xpert MTB/RIF is performed as intervention in this study (intervention group)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No immediate NAA</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Nucleic acid amplification test not requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB, and Xpert MTB/RIF is not performed as the initial diagnostic test in this study (control group). Nucleic acid amplification test may be ordered at a later point in time by clinicians as an add-on test after sputum smear microscopy</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Xpert MTB/RIF test</intervention_name>
    <description>Xpert MTB/RIF performed as the initial diagnostic test for the diagnosis of pulmonary TB</description>
    <arm_group_label>Immediate NAA as intervention</arm_group_label>
    <arm_group_label>Immediate NAA by clinician</arm_group_label>
    <other_name>nucleic acid amplification test</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All presumptive tuberculosis cases who have sputum examinations for the diagnosis of&#xD;
             pulmonary TB&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Tuberculosis cases who have been on treatment for 14 or more days who have sputum&#xD;
             examinations for follow-up&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chen-Yuan Chiang, MD,DrPhilos</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wan Fang Hospital, Taipei Medical University, Taiwan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chang-Hua Hospital</name>
      <address>
        <city>Chang-Hua</city>
        <zip>513</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Buddhist Tzu Chi General Hospital</name>
      <address>
        <city>Hualien City</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taichung Veterans General Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chest Hospital, Ministry of Health and Welfare</name>
      <address>
        <city>Tainan</city>
        <zip>717</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wan Fang Hospital, Taipei Medical University</name>
      <address>
        <city>Taipei</city>
        <zip>111</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <results_reference>
    <citation>Chiang CY, Enarson DA, Bai KJ, Suo J, Wu YC, Lin TP, Luh KT. Factors associated with a clinician's decision to stop anti-tuberculosis treatment before completion. Int J Tuberc Lung Dis. 2008 Apr;12(4):441-6.</citation>
    <PMID>18371272</PMID>
  </results_reference>
  <results_reference>
    <citation>Chiang CY, Chang CT, Chang RE, Li CT, Huang RM. Patient and health system delays in the diagnosis and treatment of tuberculosis in Southern Taiwan. Int J Tuberc Lung Dis. 2005 Sep;9(9):1006-12.</citation>
    <PMID>16158893</PMID>
  </results_reference>
  <results_reference>
    <citation>Chen CC, Chiang CY, Pan SC, Wang JY, Lin HH. Health system delay among patients with tuberculosis in Taiwan: 2003-2010. BMC Infect Dis. 2015 Nov 2;15:491. doi: 10.1186/s12879-015-1228-x.</citation>
    <PMID>26527404</PMID>
  </results_reference>
  <results_reference>
    <citation>Pan SC, Chen YC, Wang JY, Sheng WH, Lin HH, Fang CT, Chang SC. Tuberculosis in Healthcare Workers: A Matched Cohort Study in Taiwan. PLoS One. 2015 Dec 17;10(12):e0145047. doi: 10.1371/journal.pone.0145047. eCollection 2015.</citation>
    <PMID>26679188</PMID>
  </results_reference>
  <results_reference>
    <citation>Boehme CC, Nicol MP, Nabeta P, Michael JS, Gotuzzo E, Tahirli R, Gler MT, Blakemore R, Worodria W, Gray C, Huang L, Caceres T, Mehdiyev R, Raymond L, Whitelaw A, Sagadevan K, Alexander H, Albert H, Cobelens F, Cox H, Alland D, Perkins MD. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet. 2011 Apr 30;377(9776):1495-505. doi: 10.1016/S0140-6736(11)60438-8. Epub 2011 Apr 18.</citation>
    <PMID>21507477</PMID>
  </results_reference>
  <results_reference>
    <citation>Hermans S, Caldwell J, Kaplan R, Cobelens F, Wood R. The impact of the roll-out of rapid molecular diagnostic testing for tuberculosis on empirical treatment in Cape Town, South Africa. Bull World Health Organ. 2017 Aug 1;95(8):554-563. doi: 10.2471/BLT.16.185314. Epub 2017 Apr 28.</citation>
    <PMID>28804167</PMID>
  </results_reference>
  <results_reference>
    <citation>Cox H, Dickson-Hall L, Ndjeka N, Van't Hoog A, Grant A, Cobelens F, Stevens W, Nicol M. Delays and loss to follow-up before treatment of drug-resistant tuberculosis following implementation of Xpert MTB/RIF in South Africa: A retrospective cohort study. PLoS Med. 2017 Feb 21;14(2):e1002238. doi: 10.1371/journal.pmed.1002238. eCollection 2017 Feb.</citation>
    <PMID>28222095</PMID>
  </results_reference>
  <results_reference>
    <citation>Cox HS, Mbhele S, Mohess N, Whitelaw A, Muller O, Zemanay W, Little F, Azevedo V, Simpson J, Boehme CC, Nicol MP. Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: a pragmatic randomised trial. PLoS Med. 2014 Nov 25;11(11):e1001760. doi: 10.1371/journal.pmed.1001760. eCollection 2014 Nov.</citation>
    <PMID>25423041</PMID>
  </results_reference>
  <results_reference>
    <citation>Naidoo P, Dunbar R, Lombard C, du Toit E, Caldwell J, Detjen A, Squire SB, Enarson DA, Beyers N. Comparing Tuberculosis Diagnostic Yield in Smear/Culture and Xpert(R) MTB/RIF-Based Algorithms Using a Non-Randomised Stepped-Wedge Design. PLoS One. 2016 Mar 1;11(3):e0150487. doi: 10.1371/journal.pone.0150487. eCollection 2016.</citation>
    <PMID>26930400</PMID>
  </results_reference>
  <results_reference>
    <citation>Calligaro GL, Zijenah LS, Peter JG, Theron G, Buser V, McNerney R, Bara W, Bandason T, Govender U, Tomasicchio M, Smith L, Mayosi BM, Dheda K. Effect of new tuberculosis diagnostic technologies on community-based intensified case finding: a multicentre randomised controlled trial. Lancet Infect Dis. 2017 Apr;17(4):441-450. doi: 10.1016/S1473-3099(16)30384-X. Epub 2017 Jan 5.</citation>
    <PMID>28063795</PMID>
  </results_reference>
  <results_reference>
    <citation>Mbonze NB, Tabala M, Wenzi LK, Bakoko B, Brouwer M, Creswell J, Van Rie A, Behets F, Yotebieng M. Xpert((R)) MTB/RIF for smear-negative presumptive TB: impact on case notification in DR Congo. Int J Tuberc Lung Dis. 2016 Feb;20(2):240-6. doi: 10.5588/ijtld.15.0177.</citation>
    <PMID>26792478</PMID>
  </results_reference>
  <results_reference>
    <citation>Automated Real-Time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF Assay for the Diagnosis of Pulmonary and Extrapulmonary TB in Adults and Children: Policy Update. Geneva: World Health Organization; 2013. Available from http://www.ncbi.nlm.nih.gov/books/NBK258608/</citation>
    <PMID>25473701</PMID>
  </results_reference>
  <results_reference>
    <citation>Lin HH, Dowdy D, Dye C, Murray M, Cohen T. The impact of new tuberculosis diagnostics on transmission: why context matters. Bull World Health Organ. 2012 Oct 1;90(10):739-747A. doi: 10.2471/BLT.11.101436. Epub 2012 Jul 16.</citation>
    <PMID>23109741</PMID>
  </results_reference>
  <results_reference>
    <citation>Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2014 Jan 21;2014(1):CD009593. doi: 10.1002/14651858.CD009593.pub3.</citation>
    <PMID>24448973</PMID>
  </results_reference>
  <results_reference>
    <citation>Mase SR, Ramsay A, Ng V, Henry M, Hopewell PC, Cunningham J, Urbanczik R, Perkins MD, Aziz MA, Pai M. Yield of serial sputum specimen examinations in the diagnosis of pulmonary tuberculosis: a systematic review. Int J Tuberc Lung Dis. 2007 May;11(5):485-95.</citation>
    <PMID>17439669</PMID>
  </results_reference>
  <results_reference>
    <citation>Lombardi G, Di Gregori V, Girometti N, Tadolini M, Bisognin F, Dal Monte P. Diagnosis of smear-negative tuberculosis is greatly improved by Xpert MTB/RIF. PLoS One. 2017 Apr 21;12(4):e0176186. doi: 10.1371/journal.pone.0176186. eCollection 2017.</citation>
    <PMID>28430807</PMID>
  </results_reference>
  <results_reference>
    <citation>Ford I, Norrie J. Pragmatic Trials. N Engl J Med. 2016 Aug 4;375(5):454-63. doi: 10.1056/NEJMra1510059. No abstract available.</citation>
    <PMID>27518663</PMID>
  </results_reference>
  <results_reference>
    <citation>Rieder HL, Chiang CY, Rusen ID. A method to determine the utility of the third diagnostic and the second follow-up sputum smear examinations to diagnose tuberculosis cases and failures. Int J Tuberc Lung Dis. 2005 Apr;9(4):384-91.</citation>
    <PMID>15830743</PMID>
  </results_reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>May 10, 2022</last_update_submitted>
  <last_update_submitted_qc>May 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tuberculosis</keyword>
  <keyword>Xpert MTB/RIF</keyword>
  <keyword>diagnostic turnaround time</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
    <mesh_term>Tuberculosis, Pulmonary</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>individual participant data will be available on request for researchers who meet the criteria for access to confidential data</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>1 year after publication of findings</ipd_time_frame>
    <ipd_access_criteria>researchers who have been trained for research, are interested in diagnostic turnaround time of pulmonary TB, and will not use the data for commercial or publication purpose.</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/NCT04433195
org study id: N202002038
nct id: NCT04433195
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
Currently in Taiwan, most clinicians use sputum smear and culture for the diagnosis of
      pulmonary tuberculosis (TB) and apply nucleic acid amplification (NAA) test in a selected
      manner. In 2013, the World Health Organization issued conditional recommendation that Xpert
      MTB/RIF may be used rather than conventional microscopy and culture as the initial diagnostic
      test in all adults suspected of having TB. The newly published Taiwan guidelines for TB
      diagnosis and treatment has recommended NAA test, together with smear and culture, as the
      initial diagnostic test in individuals suspected of having TB. The investigators conduct a
      prospective study to investigate the use of Xpert MTB/RIF as the initial diagnostic test of
      pulmonary TB under a pragmatic trial design.
In this study the investigators will respect current practice in the use of NAA in the
      diagnosis of pulmonary TB. Clinicians may have ordered NAA as the initial diagnostic test in
      adults suspected of having pulmonary TB (group A, Immediate NAA by clinician), and the
      investigators will not intervene. For patients who do not have NAA as the initial diagnostic
      test, the investigators will use random permuted blocks to randomize these participants into
      two groups. One group will have immediate Xpert test (intervention group) as the initial
      diagnostic test and another group will continue usual care without immediate Xpert test
      (control group).

      Group A (Immediate NAA by clinician): NAA as the initial diagnostic test for pulmonary TB
      requested by clinicians.

      Group B (Immediate NAA as intervention): NAA as the initial diagnostic test for pulmonary TB
      not requested by clinicians, but is performed as intervention in this study (intervention
      group).

      Group C (No immediate NAA): NAA as the initial diagnostic test for pulmonary TB not requested
      by clinicians, and is not performed as the initial diagnostic test in this study (control
      group). NAA may be ordered at a later point in time by clinicians as an add-on test after
      sputum smear microscopy.

      The investigators will assess pulmonary TB cases detected in all groups regarding

        1. The interval between sputum examinations and initiation of ant-TB treatment.

        2. The proportion of culture confirmed pulmonary TB among all pulmonary TB cases notified.

        3. The proportion of TB patients who are advised to stop anti-TB treatment before
           completion of a treatment course.

        4. Outcome of tuberculosis treatment, including patients who die before anti-TB treatment.

      Among patients with NAA as the initial diagnostic test (Group A and Group B), the
      investigators will investigate

        1. Performance (sensitivity, specificity and predictive values) of NAA in the diagnosis of
           culture positive pulmonary TB.

        2. The incremental yield of the second and third smear in patients who have both NAA test
           and smear microscopy as the initial diagnostic test, aiming to determine the
           contribution of the second and third smear in the diagnosis of pulmonary TB.

        3. The proportion of NAA positive cases who were culture negative.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: pragmatic trial
primary purpose: Diagnostic
masking: None (Open Label)
masking description: both care providers and participants will be informed of positive results of Xpert MTB/RIF test
measure: diagnostic turnaround time
time frame: through study completion, an average of 1 year
description: The interval between sputum examinations and initiation of ant-TB treatment
measure: culture positive pulmonary TB
time frame: through study completion, an average of 1 year
description: The proportion of culture confirmed pulmonary TB among pulmonary TB cases notified
measure: change diagnosis
time frame: 12 months after the initiation of anti-tuberculosis treatment
description: The proportion of TB patients who are advised to stop anti-TB treatment before completion of a treatment course
measure: treatment outcomes
time frame: 12 months after the initiation of anti-tuberculosis treatment
description: The proportion of patients who die before anti-TB treatment, who are successfully treated, who died during treatment, who are loss-to-follow-up, who have treatment failure and who are transferred out
measure: performance of nucleic acid amplification test
time frame: through study completion, an average of 1 year
description: sensitivity, specificity and predictive values of nucleic acid amplification test in the diagnosis of culture positive pulmonary TB
measure: incremental yield
time frame: through study completion, an average of 1 year
description: The incremental yield of the second and third smear in patients who have both NAA test and smear microscopy as the initial diagnostic test, aiming to determine the contribution of the second and third smear in the diagnosis of pulmonary TB
measure: NAA false positive
time frame: through study completion, an average of 1 year
description: The proportion of nucleic acid amplification test positive cases who were culture negative
arm group label: Immediate NAA by clinician
arm group type: Active Comparator
description: Nucleic acid amplification test requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB
arm group label: Immediate NAA as intervention
arm group type: Experimental
description: Nucleic acid amplification test not requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB, but Xpert MTB/RIF is performed as intervention in this study (intervention group)
arm group label: No immediate NAA
arm group type: No Intervention
description: Nucleic acid amplification test not requested by clinicians as the initial diagnostic test for the diagnosis of pulmonary TB, and Xpert MTB/RIF is not performed as the initial diagnostic test in this study (control group). Nucleic acid amplification test may be ordered at a later point in time by clinicians as an add-on test after sputum smear microscopy
intervention type: Diagnostic Test
intervention name: Xpert MTB/RIF test
description: Xpert MTB/RIF performed as the initial diagnostic test for the diagnosis of pulmonary TB
arm group label: Immediate NAA as intervention
arm group label: Immediate NAA by clinician
other name: nucleic acid amplification test
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Chen-Yuan Chiang, MD,DrPhilos
role: Principal Investigator
affiliation: Wan Fang Hospital, Taipei Medical University, Taiwan
facility: 
facility: 
facility: 
facility: 
facility: 
country: Taiwan
citation: Chiang CY, Enarson DA, Bai KJ, Suo J, Wu YC, Lin TP, Luh KT. Factors associated with a clinician's decision to stop anti-tuberculosis treatment before completion. Int J Tuberc Lung Dis. 2008 Apr;12(4):441-6.
PMID: 18371272
citation: Chiang CY, Chang CT, Chang RE, Li CT, Huang RM. Patient and health system delays in the diagnosis and treatment of tuberculosis in Southern Taiwan. Int J Tuberc Lung Dis. 2005 Sep;9(9):1006-12.
PMID: 16158893
citation: Chen CC, Chiang CY, Pan SC, Wang JY, Lin HH. Health system delay among patients with tuberculosis in Taiwan: 2003-2010. BMC Infect Dis. 2015 Nov 2;15:491. doi: 10.1186/s12879-015-1228-x.
PMID: 26527404
citation: Pan SC, Chen YC, Wang JY, Sheng WH, Lin HH, Fang CT, Chang SC. Tuberculosis in Healthcare Workers: A Matched Cohort Study in Taiwan. PLoS One. 2015 Dec 17;10(12):e0145047. doi: 10.1371/journal.pone.0145047. eCollection 2015.
PMID: 26679188
citation: Boehme CC, Nicol MP, Nabeta P, Michael JS, Gotuzzo E, Tahirli R, Gler MT, Blakemore R, Worodria W, Gray C, Huang L, Caceres T, Mehdiyev R, Raymond L, Whitelaw A, Sagadevan K, Alexander H, Albert H, Cobelens F, Cox H, Alland D, Perkins MD. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet. 2011 Apr 30;377(9776):1495-505. doi: 10.1016/S0140-6736(11)60438-8. Epub 2011 Apr 18.
PMID: 21507477
citation: Hermans S, Caldwell J, Kaplan R, Cobelens F, Wood R. The impact of the roll-out of rapid molecular diagnostic testing for tuberculosis on empirical treatment in Cape Town, South Africa. Bull World Health Organ. 2017 Aug 1;95(8):554-563. doi: 10.2471/BLT.16.185314. Epub 2017 Apr 28.
PMID: 28804167
citation: Cox H, Dickson-Hall L, Ndjeka N, Van't Hoog A, Grant A, Cobelens F, Stevens W, Nicol M. Delays and loss to follow-up before treatment of drug-resistant tuberculosis following implementation of Xpert MTB/RIF in South Africa: A retrospective cohort study. PLoS Med. 2017 Feb 21;14(2):e1002238. doi: 10.1371/journal.pmed.1002238. eCollection 2017 Feb.
PMID: 28222095
citation: Cox HS, Mbhele S, Mohess N, Whitelaw A, Muller O, Zemanay W, Little F, Azevedo V, Simpson J, Boehme CC, Nicol MP. Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: a pragmatic randomised trial. PLoS Med. 2014 Nov 25;11(11):e1001760. doi: 10.1371/journal.pmed.1001760. eCollection 2014 Nov.
PMID: 25423041
citation: Naidoo P, Dunbar R, Lombard C, du Toit E, Caldwell J, Detjen A, Squire SB, Enarson DA, Beyers N. Comparing Tuberculosis Diagnostic Yield in Smear/Culture and Xpert(R) MTB/RIF-Based Algorithms Using a Non-Randomised Stepped-Wedge Design. PLoS One. 2016 Mar 1;11(3):e0150487. doi: 10.1371/journal.pone.0150487. eCollection 2016.
PMID: 26930400
citation: Calligaro GL, Zijenah LS, Peter JG, Theron G, Buser V, McNerney R, Bara W, Bandason T, Govender U, Tomasicchio M, Smith L, Mayosi BM, Dheda K. Effect of new tuberculosis diagnostic technologies on community-based intensified case finding: a multicentre randomised controlled trial. Lancet Infect Dis. 2017 Apr;17(4):441-450. doi: 10.1016/S1473-3099(16)30384-X. Epub 2017 Jan 5.
PMID: 28063795
citation: Mbonze NB, Tabala M, Wenzi LK, Bakoko B, Brouwer M, Creswell J, Van Rie A, Behets F, Yotebieng M. Xpert((R)) MTB/RIF for smear-negative presumptive TB: impact on case notification in DR Congo. Int J Tuberc Lung Dis. 2016 Feb;20(2):240-6. doi: 10.5588/ijtld.15.0177.
PMID: 26792478
citation: Automated Real-Time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF Assay for the Diagnosis of Pulmonary and Extrapulmonary TB in Adults and Children: Policy Update. Geneva: World Health Organization; 2013. Available from http://www.ncbi.nlm.nih.gov/books/NBK258608/
PMID: 25473701
citation: Lin HH, Dowdy D, Dye C, Murray M, Cohen T. The impact of new tuberculosis diagnostics on transmission: why context matters. Bull World Health Organ. 2012 Oct 1;90(10):739-747A. doi: 10.2471/BLT.11.101436. Epub 2012 Jul 16.
PMID: 23109741
citation: Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2014 Jan 21;2014(1):CD009593. doi: 10.1002/14651858.CD009593.pub3.
PMID: 24448973
citation: Mase SR, Ramsay A, Ng V, Henry M, Hopewell PC, Cunningham J, Urbanczik R, Perkins MD, Aziz MA, Pai M. Yield of serial sputum specimen examinations in the diagnosis of pulmonary tuberculosis: a systematic review. Int J Tuberc Lung Dis. 2007 May;11(5):485-95.
PMID: 17439669
citation: Lombardi G, Di Gregori V, Girometti N, Tadolini M, Bisognin F, Dal Monte P. Diagnosis of smear-negative tuberculosis is greatly improved by Xpert MTB/RIF. PLoS One. 2017 Apr 21;12(4):e0176186. doi: 10.1371/journal.pone.0176186. eCollection 2017.
PMID: 28430807
citation: Ford I, Norrie J. Pragmatic Trials. N Engl J Med. 2016 Aug 4;375(5):454-63. doi: 10.1056/NEJMra1510059. No abstract available.
PMID: 27518663
citation: Rieder HL, Chiang CY, Rusen ID. A method to determine the utility of the third diagnostic and the second follow-up sputum smear examinations to diagnose tuberculosis cases and failures. Int J Tuberc Lung Dis. 2005 Apr;9(4):384-91.
PMID: 15830743
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Tuberculosis, Pulmonary
sharing ipd: Yes
ipd description: individual participant data will be available on request for researchers who meet the criteria for access to confidential data
ipd info type: Study Protocol
ipd time frame: 1 year after publication of findings
ipd access criteria: researchers who have been trained for research, are interested in diagnostic turnaround time of pulmonary TB, and will not use the data for commercial or publication purpose.