<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/NCT02208427</url>
  </required_header>
  <id_info>
    <org_study_id>201309055MINC</org_study_id>
    <nct_id>NCT02208427</nct_id>
  </id_info>
  <brief_title>Toward a Safe and Reachable Preventive Therapy for LTBI: a Multicenter Randomized Controlled Study in Taiwan</brief_title>
  <official_title>Toward a Safe and Reachable Preventive Therapy for LTBI: a Multicenter Randomized Controlled Study in Taiwan</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Tuberculosis (TB) remains the most important infectious disease in the world. Keys to&#xD;
      successful control of TB is rapid diagnosis, prompt treatment, as well as effective&#xD;
      preventive therapy for contacts with latent TB infection (LTBI). Current methods for the&#xD;
      diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA).&#xD;
      For preventive therapy, the recommended regimens include daily isoniazid for 9 months and&#xD;
      daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen&#xD;
      combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven&#xD;
      of equal potency and toxicity. However, the treatment completion rate is much higher in&#xD;
      weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using&#xD;
      rifapentine-based preventive therapy can markedly increase the completion rate. However,&#xD;
      study is lacking, especially in Asia, the high endemic area of TB.&#xD;
&#xD;
      With the effort of all health care workers and public health personnel, the incidence of TB&#xD;
      in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of&#xD;
      decreasing in incidence, preventive therapy for LTBI become more and more important. However,&#xD;
      which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the&#xD;
      prospective randomized multicenter studies to compare the treatment completion rate of two&#xD;
      regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly&#xD;
      rifapentine plus high-dose isoniazid for 3 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Tuberculosis (TB) remains the most important infectious disease in the world. Keys to&#xD;
      successful control of TB is rapid diagnosis, prompt treatment, as well as effective&#xD;
      preventive therapy for contacts with latent TB infection (LTBI). Current methods for the&#xD;
      diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA).&#xD;
      For preventive therapy, the recommended regimens include daily isoniazid for 9 months and&#xD;
      daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen&#xD;
      combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven&#xD;
      of equal potency and toxicity. However, the treatment completion rate is much higher in&#xD;
      weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using&#xD;
      rifapentine-based preventive therapy can markedly increase the completion rate. However,&#xD;
      study is lacking, especially in Asia, the high endemic area of TB.&#xD;
&#xD;
      With the effort of all health care workers and public health personnel, the incidence of TB&#xD;
      in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of&#xD;
      decreasing in incidence, preventive therapy for LTBI become more and more important. However,&#xD;
      which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the&#xD;
      prospective randomized multicenter studies to compare the treatment completion rate of two&#xD;
      regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly&#xD;
      rifapentine plus high-dose isoniazid for 3 months.&#xD;
&#xD;
      Specific Aims:&#xD;
&#xD;
        1. Understanding which of the two preventive regimens has the highest completion rate under&#xD;
           supervision.&#xD;
&#xD;
        2. Understanding the reasons of interruption in preventive therapy.&#xD;
&#xD;
        3. Comparing the side effect profile of the two preventive regimens in Taiwan.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      In this prospective multicenter study, we will enroll close contacts aged &gt;=12 with positive&#xD;
      TST. Chest radiography and sputum studies, if necessary, will be performed to exclude active&#xD;
      pulmonary TB. After performing baseline IGRA, participants will be randomized into 2 groups&#xD;
      with different preventive regimens. The first regimen is daily isoniazid for 9 months. The&#xD;
      second is weekly rifapentine plus high-dose isoniazid for 3 months. The primary outcome is&#xD;
      treatment completion rate of the two preventive regimens. The secondary outcome is toxicity.&#xD;
      All participant will be followed for 2 years and screen for the development of active&#xD;
      pulmonary TB by chest radiography and sputum studies if necessary. The reasons for treatment&#xD;
      incompletion will be recorded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2016</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>completion rate</measure>
    <time_frame>2 years</time_frame>
    <description>This prospective randomized interventional study is aimed to assess the completion rate of two different preventive regimens for LTBI by intent-to-treat analysis. Interruption of preventive therapy due to any reasons will be considered as incompletion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>side effect</measure>
    <time_frame>3 months in the 3M_RH group and 9 months in the 9M_INH group</time_frame>
    <description>To evaluate the side effect profile (especially hepatotoxicity, defined as AST and/or ALT ≥2 ULN) of the two preventive regimens</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>interruption</measure>
    <time_frame>3 months in the 3M_RH group and 9 months in the 9M_INH group</time_frame>
    <description>To calculate the number of participants with interruption in preventive therapy and to know the reasons of interruption by questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>active TB</measure>
    <time_frame>2 years after enrollment</time_frame>
    <description>To know the rate of active TB within subsequent 2 years</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">283</enrollment>
  <condition>Latent Tuberculosis Infection</condition>
  <arm_group>
    <arm_group_label>3M_RH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rifapentine and Isoniazid for 3 months: weekly oral rifapentine 15 mg/kg plus isoniazid 15 mg/kg for 12 doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>9M_INH</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Isoniazid for 9 months: daily oral isoniazid 5 mg/kg for 9 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifapentine and Isoniazid for 3 months</intervention_name>
    <description>weekly oral Rifapentine 15 mg/kg plus Isoniazid 15 mg/kg for 12 doses</description>
    <arm_group_label>3M_RH</arm_group_label>
    <other_name>Priftin</other_name>
    <other_name>Isoniazid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isoniazid for 9 months</intervention_name>
    <description>daily oral Isoniazid 5 mg/kg for 9 months under supervision (conventional IPT)</description>
    <arm_group_label>9M_INH</arm_group_label>
    <other_name>Isoniazid</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Household contacts of TB or TB contacts in schools or densely-populated institutes&#xD;
&#xD;
          -  Age ≥12 year-old&#xD;
&#xD;
          -  Index case having smear-positive pulmonary TB&#xD;
&#xD;
          -  Contact with index case for &gt;8 hours within single day or &gt;40 hours within total&#xD;
             transmissible period&#xD;
&#xD;
          -  TST ≥10 mm within one month&#xD;
&#xD;
          -  Born in 1986 or after (not applicable in the National Taiwan University Hospital&#xD;
             Hsin-Chu branch and Chang-Hua Hospital)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinical or radiographic evidence of active TB&#xD;
&#xD;
          -  Index case having culture-negative pulmonary TB&#xD;
&#xD;
          -  Index case having Isoniazid or Rifampin-resistant TB&#xD;
&#xD;
          -  Receiving medications with significant interactions with Isoniazid, Rifampin, or&#xD;
             Rifapentine&#xD;
&#xD;
          -  Allergy to Isoniazid, Rifampin, or Rifapentine&#xD;
&#xD;
          -  Sero-positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection&#xD;
&#xD;
          -  Documented liver cirrhosis&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Receiving immunosuppressants&#xD;
&#xD;
          -  Receiving biological agents&#xD;
&#xD;
          -  Hemoglobin &lt;8 g/dL&#xD;
&#xD;
          -  Neutrophil &lt;750000 /mL&#xD;
&#xD;
          -  Total bilirubin &gt;2.5 mg/dL&#xD;
&#xD;
          -  Aspartic transaminase (AST) or alanine transaminase (ALT) &gt;2 folds of upper limit of&#xD;
             normal (ULN)&#xD;
&#xD;
          -  Pregnant or breast-feeding&#xD;
&#xD;
          -  Life expectancy &lt;3 years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jann-Yuan Wang, MD. PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>August 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <last_update_submitted>December 14, 2016</last_update_submitted>
  <last_update_submitted_qc>December 14, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>isoniazid, LTBI, rifapentine, TST</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Isoniazid</mesh_term>
    <mesh_term>Rifapentine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02208427
org study id: 201309055MINC
nct id: NCT02208427
lead sponsor: 
has dmc: Yes
Background:

      Tuberculosis (TB) remains the most important infectious disease in the world. Keys to
      successful control of TB is rapid diagnosis, prompt treatment, as well as effective
      preventive therapy for contacts with latent TB infection (LTBI). Current methods for the
      diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA).
      For preventive therapy, the recommended regimens include daily isoniazid for 9 months and
      daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen
      combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven
      of equal potency and toxicity. However, the treatment completion rate is much higher in
      weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using
      rifapentine-based preventive therapy can markedly increase the completion rate. However,
      study is lacking, especially in Asia, the high endemic area of TB.

      With the effort of all health care workers and public health personnel, the incidence of TB
      in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of
      decreasing in incidence, preventive therapy for LTBI become more and more important. However,
      which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the
      prospective randomized multicenter studies to compare the treatment completion rate of two
      regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly
      rifapentine plus high-dose isoniazid for 3 months.
Background:

      Tuberculosis (TB) remains the most important infectious disease in the world. Keys to
      successful control of TB is rapid diagnosis, prompt treatment, as well as effective
      preventive therapy for contacts with latent TB infection (LTBI). Current methods for the
      diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA).
      For preventive therapy, the recommended regimens include daily isoniazid for 9 months and
      daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen
      combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven
      of equal potency and toxicity. However, the treatment completion rate is much higher in
      weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using
      rifapentine-based preventive therapy can markedly increase the completion rate. However,
      study is lacking, especially in Asia, the high endemic area of TB.

      With the effort of all health care workers and public health personnel, the incidence of TB
      in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of
      decreasing in incidence, preventive therapy for LTBI become more and more important. However,
      which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the
      prospective randomized multicenter studies to compare the treatment completion rate of two
      regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly
      rifapentine plus high-dose isoniazid for 3 months.

      Specific Aims:

        1. Understanding which of the two preventive regimens has the highest completion rate under
           supervision.

        2. Understanding the reasons of interruption in preventive therapy.

        3. Comparing the side effect profile of the two preventive regimens in Taiwan.

      Methods:

      In this prospective multicenter study, we will enroll close contacts aged >=12 with positive
      TST. Chest radiography and sputum studies, if necessary, will be performed to exclude active
      pulmonary TB. After performing baseline IGRA, participants will be randomized into 2 groups
      with different preventive regimens. The first regimen is daily isoniazid for 9 months. The
      second is weekly rifapentine plus high-dose isoniazid for 3 months. The primary outcome is
      treatment completion rate of the two preventive regimens. The secondary outcome is toxicity.
      All participant will be followed for 2 years and screen for the development of active
      pulmonary TB by chest radiography and sputum studies if necessary. The reasons for treatment
      incompletion will be recorded.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: completion rate
time frame: 2 years
description: This prospective randomized interventional study is aimed to assess the completion rate of two different preventive regimens for LTBI by intent-to-treat analysis. Interruption of preventive therapy due to any reasons will be considered as incompletion.
measure: side effect
time frame: 3 months in the 3M_RH group and 9 months in the 9M_INH group
description: To evaluate the side effect profile (especially hepatotoxicity, defined as AST and/or ALT ≥2 ULN) of the two preventive regimens
measure: interruption
time frame: 3 months in the 3M_RH group and 9 months in the 9M_INH group
description: To calculate the number of participants with interruption in preventive therapy and to know the reasons of interruption by questionnaire
measure: active TB
time frame: 2 years after enrollment
description: To know the rate of active TB within subsequent 2 years
arm group label: 3M_RH
arm group type: Experimental
description: Rifapentine and Isoniazid for 3 months: weekly oral rifapentine 15 mg/kg plus isoniazid 15 mg/kg for 12 doses
arm group label: 9M_INH
arm group type: Active Comparator
description: Isoniazid for 9 months: daily oral isoniazid 5 mg/kg for 9 months
intervention type: Drug
intervention name: Rifapentine and Isoniazid for 3 months
description: weekly oral Rifapentine 15 mg/kg plus Isoniazid 15 mg/kg for 12 doses
arm group label: 3M_RH
other name: Priftin
other name: Isoniazid
intervention type: Drug
intervention name: Isoniazid for 9 months
description: daily oral Isoniazid 5 mg/kg for 9 months under supervision (conventional IPT)
arm group label: 9M_INH
other name: Isoniazid
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Jann-Yuan Wang, MD. PhD.
role: Principal Investigator
affiliation: National Taiwan University Hospital
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Latent Tuberculosis
mesh term: Isoniazid
mesh term: Rifapentine
sharing ipd: Undecided