<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/NCT03042754</url>
  </required_header>
  <id_info>
    <org_study_id>TB NRU</org_study_id>
    <nct_id>NCT03042754</nct_id>
  </id_info>
  <brief_title>Improve Treatment Outcomes for Tuberculosis Infection in Tertiary Care Hospitals</brief_title>
  <official_title>Improve Treatment Outcomes for Tuberculosis Infection in Tertiary Care Hospitals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The HIV Netherlands Australia Thailand Research Collaboration</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chulalongkorn University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bamrasnaradura Infectious Diseases Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rajavithi Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The HIV Netherlands Australia Thailand Research Collaboration</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>
      Early diagnosis can contribute to good treatment outcomes and isolate infection control.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is conducted into 2 parts: prospective and retrospective.&#xD;
&#xD;
      The prospective study evaluated the use of Xpert MTB/RIF. The study was conducted at three&#xD;
      large tertiary care hospitals: the King Chulalongkorn Memorial Hospital, Rajavithi Hospital&#xD;
      and Bamrasnaradura Infectious Diseases Institute. Only pulmonologists and infectious disease&#xD;
      physicians with extensive experience in TB participated in the study. Patients who had&#xD;
      suspected PTB were enrolled into the study. Expectorated sputum were collected and&#xD;
      transferred to the central laboratory, Chulalongkorn Research Center (CRC) Laboratory, King&#xD;
      Chulalongkorn Memorial Hospital. Each sample was divided into two parts; one part for the&#xD;
      Xpert MTB/RIF (Cepheid) and another part for mycobacterial culture. Drug susceptibility tests&#xD;
      for streptomycin, isoniazid, rifampicin and ethambutol were performed with rapid qualitative&#xD;
      procedure (BACTEC™ MGIT™ 960 SIRE Kit) and semi-automated system (BACTEC™ MGIT™ 960 System).&#xD;
      Discordant results of MGIT and Xpert were retested with the rpoB gene sequencing system. All&#xD;
      PTB patients were promptly treated with anti-TB drug regimens as WHO's recommendation. All&#xD;
      patients had HIV testing done and CD4 cell counts were obtained for all HIV-infected&#xD;
      patients. Antiretroviral treatment and prophylaxis for opportunistic infections were&#xD;
      prescribed as standard treatment guideline for patients with HIV/TB co-infection. The&#xD;
      patients were followed until completion of TB treatment or change in the diagnosis. The WHO&#xD;
      definitions for cure, completed treatment, dead, default or treatment failure were used to&#xD;
      define the outcome of treatment.&#xD;
&#xD;
      The authors , therefore, evaluated the utility of Xpert MTB/RIF in Thailand, prior to&#xD;
      nation-wide implementation. In summary, our real-life cohort study use Xpert MTB/RIF for&#xD;
      early diagnosis of PTB and rifampicin resistance in high TB burden country outside of the&#xD;
      African region. The results may be beneficial for guiding the policy makers, especially the&#xD;
      National Tuberculosis Programme (NTP) to control TB transmission, as the country move towards&#xD;
      universal use of Xpert MTB/RIF.&#xD;
&#xD;
      The retrospective study assessed the urine LAM test which has not been evaluated in&#xD;
      non-HIV-infected immunocompromised Asians with disseminated TB and non-disseminated TB (TB&#xD;
      located in one organ) but has a poor sensitivity and specificity for detecting pulmonary TB&#xD;
      patients without HIV infection. On that account, the authors evaluated the applicability and&#xD;
      efficacy of TB diagnosis by using the urine from confirmed cultured TB cases with various&#xD;
      immune response conditions, such as HIV-infected, non-HIV-infected and non-HIV-infected&#xD;
      immunocompromised patients. The authors found that the sensitivity of the urine LAM in&#xD;
      HIV-infected and non-HIV-infected patients were similar to previous reports. This confirmed&#xD;
      that the urine LAM cannot be used alone to screen for TB. However, it can be used in&#xD;
      conjunction with the culture and AFB smear test for patients co-infected with HIV with very&#xD;
      low CD4 count. The urine LAM test is especially helpful in cases where the smear is negative&#xD;
      in probable-TB patients. For this reason, the urine LAM test is attractive because it is not&#xD;
      invasive, and the samples needed can be easily collected from these types of disseminated&#xD;
      patients with and without HIV.&#xD;
&#xD;
      Aside from that, the urine LAM test can be used in those severely ill patients, regardless of&#xD;
      HIV infection, where it is difficult to physically collect the sputum and paucibacillary&#xD;
      samples. The PPV was over 80% for those infected with HIV and up to 100% in non-HIV-infected&#xD;
      patients. For physicians, the PPV is more useful than the sensitivity and specificity of the&#xD;
      assay because it will answer the question how likely the patient with a positive result from&#xD;
      the urine LAM test will have TB or not. A high PPV can accurately guide the physicians to&#xD;
      confidentially prescribe the TB medications which are crucial, especially among co-infected&#xD;
      patients that are severely ill. For this reason, the urine LAM test seems to be a great&#xD;
      point-of-care test that can easily be incorporated with the AFB smear and culture test for&#xD;
      the Asian population. Furthermore, this study demonstrated that a positive urine LAM test&#xD;
      result was significantly associated with death, especially those with HIV infection. This&#xD;
      association is much stronger in patients with very low CD4 counts. The findings from this&#xD;
      study suggest the possible use of the urine LAM test with the AFB smear and culture in&#xD;
      resource-limited countries in diagnosing TB in advanced HIV and non-HIV-infected patients&#xD;
      with TB. This promising diagnostic tool can increase the yield of TB diagnosis and predict&#xD;
      the mortality rate of TB infection, particularly in advanced HIV patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 6, 2011</start_date>
  <completion_date type="Anticipated">December 1, 2030</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2030</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>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sensitivity of sputum from patients suspected with TB</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Sensitivity of urine LAM from patients suspected with TB</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">6000</enrollment>
  <condition>Tuberculosis</condition>
  <arm_group>
    <arm_group_label>suspected TB</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients suspected with TB will be sent for XpertMTB/RIF and urine LAM test</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>XpertMTB/RIF</intervention_name>
    <arm_group_label>suspected TB</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with suspected TB&#xD;
&#xD;
          -  patients that can give us sputum and urine specimens&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  refuse to provide written informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gompol Suwanpimolkul, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chulalongkorn University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kamon Kawkitinarong, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chulalongkorn University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Pirapon J Ohata, BS</last_name>
    <email>juneohata4@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Chulalongkorn University</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Gompol Suwanpimolkul, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kamon Kawkitinarong, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>HIV-NAT, Thai Red Cross AIDS Research Centre</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pirapon J Ohata, BS</last_name>
      <email>juneohata4@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Anchalee Avihinsanon, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rajavithi Hospital</name>
      <address>
        <city>Bangkok</city>
        <country>Thailand</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Pairaj Kateruttanakul, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Bamrasnaradura Institute</name>
      <address>
        <city>Nonthaburi</city>
        <zip>11000</zip>
        <country>Thailand</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Weerawat Manosutti, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <link>
    <url>http://www.hivnat.org</url>
    <description>Related Info</description>
  </link>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>February 1, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>March 22, 2022</last_update_submitted>
  <last_update_submitted_qc>March 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>LAM</keyword>
  <keyword>XpertMTB/RIF</keyword>
  <keyword>treatment outcome</keyword>
  <keyword>Microbacterial tuberculosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
    <mesh_term>Latent Tuberculosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>only for auditing/monitoring process as needed</ipd_description>
  </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/NCT03042754
org study id: TB NRU
nct id: NCT03042754
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Early diagnosis can contribute to good treatment outcomes and isolate infection control.
This study is conducted into 2 parts: prospective and retrospective.

      The prospective study evaluated the use of Xpert MTB/RIF. The study was conducted at three
      large tertiary care hospitals: the King Chulalongkorn Memorial Hospital, Rajavithi Hospital
      and Bamrasnaradura Infectious Diseases Institute. Only pulmonologists and infectious disease
      physicians with extensive experience in TB participated in the study. Patients who had
      suspected PTB were enrolled into the study. Expectorated sputum were collected and
      transferred to the central laboratory, Chulalongkorn Research Center (CRC) Laboratory, King
      Chulalongkorn Memorial Hospital. Each sample was divided into two parts; one part for the
      Xpert MTB/RIF (Cepheid) and another part for mycobacterial culture. Drug susceptibility tests
      for streptomycin, isoniazid, rifampicin and ethambutol were performed with rapid qualitative
      procedure (BACTEC™ MGIT™ 960 SIRE Kit) and semi-automated system (BACTEC™ MGIT™ 960 System).
      Discordant results of MGIT and Xpert were retested with the rpoB gene sequencing system. All
      PTB patients were promptly treated with anti-TB drug regimens as WHO's recommendation. All
      patients had HIV testing done and CD4 cell counts were obtained for all HIV-infected
      patients. Antiretroviral treatment and prophylaxis for opportunistic infections were
      prescribed as standard treatment guideline for patients with HIV/TB co-infection. The
      patients were followed until completion of TB treatment or change in the diagnosis. The WHO
      definitions for cure, completed treatment, dead, default or treatment failure were used to
      define the outcome of treatment.

      The authors , therefore, evaluated the utility of Xpert MTB/RIF in Thailand, prior to
      nation-wide implementation. In summary, our real-life cohort study use Xpert MTB/RIF for
      early diagnosis of PTB and rifampicin resistance in high TB burden country outside of the
      African region. The results may be beneficial for guiding the policy makers, especially the
      National Tuberculosis Programme (NTP) to control TB transmission, as the country move towards
      universal use of Xpert MTB/RIF.

      The retrospective study assessed the urine LAM test which has not been evaluated in
      non-HIV-infected immunocompromised Asians with disseminated TB and non-disseminated TB (TB
      located in one organ) but has a poor sensitivity and specificity for detecting pulmonary TB
      patients without HIV infection. On that account, the authors evaluated the applicability and
      efficacy of TB diagnosis by using the urine from confirmed cultured TB cases with various
      immune response conditions, such as HIV-infected, non-HIV-infected and non-HIV-infected
      immunocompromised patients. The authors found that the sensitivity of the urine LAM in
      HIV-infected and non-HIV-infected patients were similar to previous reports. This confirmed
      that the urine LAM cannot be used alone to screen for TB. However, it can be used in
      conjunction with the culture and AFB smear test for patients co-infected with HIV with very
      low CD4 count. The urine LAM test is especially helpful in cases where the smear is negative
      in probable-TB patients. For this reason, the urine LAM test is attractive because it is not
      invasive, and the samples needed can be easily collected from these types of disseminated
      patients with and without HIV.

      Aside from that, the urine LAM test can be used in those severely ill patients, regardless of
      HIV infection, where it is difficult to physically collect the sputum and paucibacillary
      samples. The PPV was over 80% for those infected with HIV and up to 100% in non-HIV-infected
      patients. For physicians, the PPV is more useful than the sensitivity and specificity of the
      assay because it will answer the question how likely the patient with a positive result from
      the urine LAM test will have TB or not. A high PPV can accurately guide the physicians to
      confidentially prescribe the TB medications which are crucial, especially among co-infected
      patients that are severely ill. For this reason, the urine LAM test seems to be a great
      point-of-care test that can easily be incorporated with the AFB smear and culture test for
      the Asian population. Furthermore, this study demonstrated that a positive urine LAM test
      result was significantly associated with death, especially those with HIV infection. This
      association is much stronger in patients with very low CD4 counts. The findings from this
      study suggest the possible use of the urine LAM test with the AFB smear and culture in
      resource-limited countries in diagnosing TB in advanced HIV and non-HIV-infected patients
      with TB. This promising diagnostic tool can increase the yield of TB diagnosis and predict
      the mortality rate of TB infection, particularly in advanced HIV patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Sensitivity of sputum from patients suspected with TB
time frame: 2 years
measure: Sensitivity of urine LAM from patients suspected with TB
time frame: 1 year
arm group label: suspected TB
arm group type: Other
description: Patients suspected with TB will be sent for XpertMTB/RIF and urine LAM test
intervention type: Diagnostic Test
intervention name: XpertMTB/RIF
arm group label: suspected TB
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gompol Suwanpimolkul, MD
role: Principal Investigator
affiliation: Chulalongkorn University
last name: Kamon Kawkitinarong, MD
role: Principal Investigator
affiliation: Chulalongkorn University
last name: Pirapon J Ohata, BS
email: juneohata4@gmail.com
facility: 
status: Recruiting
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
country: Thailand
url: http://www.hivnat.org
description: Related Info
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Latent Tuberculosis
sharing ipd: No
ipd description: only for auditing/monitoring process as needed