<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/NCT02980016</url>
  </required_header>
  <id_info>
    <org_study_id>3HP-AUR1-1-170</org_study_id>
    <nct_id>NCT02980016</nct_id>
  </id_info>
  <brief_title>Evaluation of the Effect of 3HP vs Periodic 3HP vs 6H in HIV-Positive Individuals</brief_title>
  <acronym>WHIP3TB</acronym>
  <official_title>A Randomised, Pragmatic, Open-Label Trial To Evaluate The Effect Of Three Months Of High Dose Rifapentine Plus Isoniazid Administered As A Single Round Or Given Annually In HIV-Positive Individuals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Aurum Institute NPC</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Aurum Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>London School of Hygiene and Tropical Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Aurum Institute NPC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a parallel, two part, open label, individually randomized, pragmatic trial&#xD;
      among HIV-positive individuals. Part A compares a single round of weekly high dose&#xD;
      rifapentine plus isoniazid for three months (3HP) to six months of daily isoniazid (6H). Part&#xD;
      B compares periodic 3HP (p3HP) to a single round of 3HP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Part A: A randomised controlled trial of 3HP vs 6H [enrollment starts concurrently with Part&#xD;
      B]&#xD;
&#xD;
      Justification: The World Health Organization (WHO) recommends at least six months of&#xD;
      isoniazid (6H) for persons living with HIV. However, 6H remains poorly implemented in most&#xD;
      high burden tuberculosis (TB) countries. In its 2015 guidelines, WHO includes 3HP as an&#xD;
      latent tuberculosis infection (LTBI) treatment option for high-income and upper middle-income&#xD;
      countries with TB incidence rates &lt;100/100,000. One trial comparing 3HP to 6H in a high&#xD;
      burden country suggests that a single round of 3HP has less toxicity, better treatment&#xD;
      completion rates, and similar efficacy in preventing TB. The purpose of comparing a single&#xD;
      round of 3HP to 6H is to demonstrate the feasibility of implementing 3HP in high burden&#xD;
      countries, to explore its safety and effectiveness, and to generate evidence to guide a WHO&#xD;
      recommendation for the use of 3HP in high burden settings.&#xD;
&#xD;
      Sample size: If we assume 85% of patients in the 6H arm complete treatment as defined above,&#xD;
      with 400 patients in the 6H arm and 3600 patients in the 3HP arm we will have 82% power to&#xD;
      detect an increase in treatment completion of 5% (To -90%) in the 3HP arm. If treatment&#xD;
      completion in the 6H arm is 75%, we will have approximately 90% power to detect an increase&#xD;
      in treatment completion of 7% in the 3HP arm.&#xD;
&#xD;
      Analysis: Treatment completion will be compared by study arm using Fishers Exact test, and&#xD;
      associated risk difference and 95% confidence interval (CI).&#xD;
&#xD;
      Part B: A randomised controlled trial of 3HP vs p3HP [enrollment starts concurrently with&#xD;
      Part A]&#xD;
&#xD;
      Justification: A single round of 3HP has been shown to be non-inferior to 9 months of&#xD;
      isoniazid (9H) in persons at high risk of developing TB in low and middle TB burden settings.&#xD;
      Similarly, a single round of 3HP has demonstrated similar efficacy in preventing active TB&#xD;
      when compared to 6H among HIV-positive, tuberculin skin test (TST)-positive adults in the&#xD;
      high burden setting of South Africa. In high burden settings, 6H and 3HP provide protection&#xD;
      of limited duration probably due to high ongoing transmission and reinfection. Continuous&#xD;
      isoniazid preventive therapy has been shown to provide more durable protection in high burden&#xD;
      settings, but is not currently policy outside of a handful of countries, and the actual&#xD;
      uptake is poor. Giving 3HP periodically may provide durable protection, be easier for health&#xD;
      systems to implement, and may be associated with better adherence and fewer side effects.&#xD;
&#xD;
      Sample size: Assuming a cumulative TB incidence of 5% over 2 years in the control (3HP) arm,&#xD;
      an overall loss to follow-up of 10% by year 2, a two-sided type I error of 5%, 1:1&#xD;
      randomisation, a superiority comparison and 1800 participants per arm, we have 80% power to&#xD;
      detect a 40% reduction in cumulative TB incidence from months 0 to 24.&#xD;
&#xD;
      Analysis: The analysis will compare 3HP and p3HP with two years of follow up. Cumulative TB&#xD;
      incidence will be determined by combining incident TB cases identified over the 24 months of&#xD;
      follow up AND prevalent TB cases identified at the 12 and 24 month culture survey. Data will&#xD;
      be reported as a risk difference and odds ratio and their associated 95% CIs, adjusting for&#xD;
      randomisation strata. The secondary outcome comparing the effectiveness of p3HP to 3HP from&#xD;
      month 13 to 24 (during which time the greatest effect is likely to be evident) will be&#xD;
      conducting using the same analytic methods. The results of Part B will be disseminated&#xD;
      subsequent to the results of Part A.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Actual">October 18, 2019</completion_date>
  <primary_completion_date type="Actual">October 18, 2019</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>Treatment completion (part A)</measure>
    <time_frame>1 year</time_frame>
    <description>Number of participants without evidence of active TB at enrollment who complete treatment, defined as:&#xD;
Proportion of participants in 3HP group self-reporting treatment completion of ≥11 doses in a 16-week period&#xD;
; Proportion or participants in 6H group self-reporting treatment completion of ≥167 doses over an 34 week (8-month) period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TB incidence (part B)</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants without evidence of active TB at enrollment who are diagnosed with active TB meeting the definition: Confirmed tuberculosis: Culture-positive, Xpert MTB/RIF-positive, or smear-positive for M. tuberculosis from any site in adults and children OR Clinical tuberculosis: Started on treatment for TB in adults and children</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>TB incidence (part A)</measure>
    <time_frame>1 year</time_frame>
    <description>Number of participants without evidence of active TB at enrollment who are diagnosed with active TB meeting the definition: Confirmed tuberculosis: Culture-positive, Xpert MTB/RIF-positive, or smear-positive for M. tuberculosis from any site in adults and children OR Clinical tuberculosis: Started on treatment for TB in adults and children</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality (part A)</measure>
    <time_frame>1 year</time_frame>
    <description>Number of participants without evidence of active TB at enrollment who die from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Permanent discontinuation of therapy due to treatment-related adverse events (part A)</measure>
    <time_frame>1 year</time_frame>
    <description>Number of participants without evidence of active TB at enrollment who permanently discontinue therapy due to an adverse drug reaction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TB incidence (part B)</measure>
    <time_frame>1 year</time_frame>
    <description>Number of participants without evidence of active TB during enrollment who are diagnosed with active TB meeting during the second year of follow-up. The definition of active TB is: Confirmed tuberculosis: Culture-positive, Xpert MTB/RIF-positive, or smear-positive for M. tuberculosis from any site in adults and children OR Clinical tuberculosis: Started on treatment for TB in adults and children</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment completion (part B)</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants without evidence of active TB at enrollment who complete treatment, defined as: Proportion of participants in 3HP group self-reporting treatment completion of ≥11 doses in a 16-week period; Proportion or participants in p3HP group self-reporting treatment completion of ≥22 doses over two annual 16-week periods</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality (part B)</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants without evidence of active TB at enrollment who die from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Permanent discontinuation of therapy due to treatment-related adverse events (part B)</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants without evidence of active TB at enrollment who permanently discontinue therapy due to an adverse drug reaction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost per TB case prevented</measure>
    <time_frame>2 years</time_frame>
    <description>Cost per TB case prevented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost per death averted</measure>
    <time_frame>2 years</time_frame>
    <description>Cost per death averted</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost per disability adjusted life year (DALY) averted by study arm</measure>
    <time_frame>2 years</time_frame>
    <description>Cost per disability adjusted life year (DALY) averted by study arm</description>
  </secondary_outcome>
  <other_outcome>
    <measure>IGRA conversions (part A)</measure>
    <time_frame>1 year</time_frame>
    <description>Number of IGRA-negative participants without evidence of active TB at enrollment with the occurrence of IGRA conversions at the end of year 1</description>
  </other_outcome>
  <other_outcome>
    <measure>IGRA reversions (part A)</measure>
    <time_frame>1 year</time_frame>
    <description>Number of IGRA-positive participants without evidence of active TB at enrollment with the occurrence of IGRA reversions at the end of year 1</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of TB resistant to isoniazid and/or rifapentine</measure>
    <time_frame>2 years</time_frame>
    <description>Number of individuals without evidence of active TB at enrollment who are diagnosed with active TB resistant to isoniazid and/or rifapentine</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">4027</enrollment>
  <condition>Tuberculosis</condition>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>3HP (rifapentine + isoniazid)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Once weekly rifapentine (at a dose of 900 mg) plus isoniazid (at a dose of 900 mg), (with adjustment for participants weighing ≤50 kg) given for 12 weeks in Study Year 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>p3HP (rifapentine + isoniazid)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Once weekly rifapentine (at a dose of 900 mg) plus isoniazid (at a dose of 900 mg), (with adjustment for participants weighing ≤50 kg) given for 12 weeks in Study Years 1 and 2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>6H</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Daily self-administered isoniazid (at a dose of 300 mg/daily) (with adjustment for participants weighing ≤24 kg) given for 26 weeks (6 months) in Study Year 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rifapentine + isoniazid</intervention_name>
    <description>Rifapentine + isoniazid Once weekly rifapentine (at a dose of 900 mg) plus isoniazid (at a dose of 900 mg), with adjustment for participants weighing ≤50 kg</description>
    <arm_group_label>3HP (rifapentine + isoniazid)</arm_group_label>
    <arm_group_label>p3HP (rifapentine + isoniazid)</arm_group_label>
    <other_name>Priftin (rifapentine)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isoniazid</intervention_name>
    <description>Daily self-administered isoniazid (at a dose of 300 mg/daily), with adjustment for participants weighing ≤24 kg</description>
    <arm_group_label>6H</arm_group_label>
    <other_name>Winthrop (isoniazid)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least two years of age&#xD;
&#xD;
          -  Known HIV infection&#xD;
&#xD;
          -  Antiretroviral therapy (ART) ineligible or on ART for ≥3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Confirmed or suspected TB disease&#xD;
&#xD;
          -  Likely to move from the study area during the study period&#xD;
&#xD;
          -  Known exposure to TB cases with known or suspected resistance to isoniazid or&#xD;
             rifampicin in the source case&#xD;
&#xD;
          -  TB treatment within the past year&#xD;
&#xD;
          -  TB preventive therapy within the last year&#xD;
&#xD;
          -  Sensitivity or intolerance to isoniazid or rifamycins&#xD;
&#xD;
          -  Suspected acute hepatitis or known chronic liver disease&#xD;
&#xD;
          -  ALT/AST &gt;5 times the upper limit of normal (regardless of symptoms of hepatitis)&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Women of childbearing potential who are unable or unwilling to use contraception&#xD;
&#xD;
          -  Self-reported alcohol use exceeding 28 units per week for men, or 21 units for women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gavin Churchyard, MBBCh, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aurum Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Aurum Institute NPC</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2193</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <reference>
    <citation>Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, Hackman J, Hamilton CD, Menzies D, Kerrigan A, Weis SE, Weiner M, Wing D, Conde MB, Bozeman L, Horsburgh CR Jr, Chaisson RE; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011 Dec 8;365(23):2155-66. doi: 10.1056/NEJMoa1104875.</citation>
    <PMID>22150035</PMID>
  </reference>
  <reference>
    <citation>Sterling TR, Moro RN, Borisov AS, Phillips E, Shepherd G, Adkinson NF, Weis S, Ho C, Villarino ME; Tuberculosis Trials Consortium. Flu-like and Other Systemic Drug Reactions Among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study. Clin Infect Dis. 2015 Aug 15;61(4):527-35. doi: 10.1093/cid/civ323. Epub 2015 Apr 22.</citation>
    <PMID>25904367</PMID>
  </reference>
  <reference>
    <citation>Sterling TR, Benson CA, Shang N. Tolerability among HIV-infected persons of three months of once-weekly rifapentine + INH (3HP) vs. 9 months of daily INH (9H) for treatment of latent tuberculosis infection. In: International AIDS Society Conference. Washington, DC.; 2012.</citation>
  </reference>
  <reference>
    <citation>Martinson NA, Barnes GL, Moulton LH, Msandiwa R, Hausler H, Ram M, McIntyre JA, Gray GE, Chaisson RE. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011 Jul 7;365(1):11-20. doi: 10.1056/NEJMoa1005136.</citation>
    <PMID>21732833</PMID>
  </reference>
  <reference>
    <citation>Villarino ME, Scott NA, Weis SE, Weiner M, Conde MB, Jones B, Nachman S, Oliveira R, Moro RN, Shang N, Goldberg SV, Sterling TR; International Maternal Pediatric and Adolescents AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr. 2015 Mar;169(3):247-55. doi: 10.1001/jamapediatrics.2014.3158. Erratum In: JAMA Pediatr. 2015 Sep;169(9):878.</citation>
    <PMID>25580725</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <last_update_submitted>October 29, 2019</last_update_submitted>
  <last_update_submitted_qc>October 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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>
    <mesh_term>Rifampin</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/NCT02980016
org study id: 3HP-AUR1-1-170
nct id: NCT02980016
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
This study is a parallel, two part, open label, individually randomized, pragmatic trial
      among HIV-positive individuals. Part A compares a single round of weekly high dose
      rifapentine plus isoniazid for three months (3HP) to six months of daily isoniazid (6H). Part
      B compares periodic 3HP (p3HP) to a single round of 3HP.
Part A: A randomised controlled trial of 3HP vs 6H [enrollment starts concurrently with Part
      B]

      Justification: The World Health Organization (WHO) recommends at least six months of
      isoniazid (6H) for persons living with HIV. However, 6H remains poorly implemented in most
      high burden tuberculosis (TB) countries. In its 2015 guidelines, WHO includes 3HP as an
      latent tuberculosis infection (LTBI) treatment option for high-income and upper middle-income
      countries with TB incidence rates <100/100,000. One trial comparing 3HP to 6H in a high
      burden country suggests that a single round of 3HP has less toxicity, better treatment
      completion rates, and similar efficacy in preventing TB. The purpose of comparing a single
      round of 3HP to 6H is to demonstrate the feasibility of implementing 3HP in high burden
      countries, to explore its safety and effectiveness, and to generate evidence to guide a WHO
      recommendation for the use of 3HP in high burden settings.

      Sample size: If we assume 85% of patients in the 6H arm complete treatment as defined above,
      with 400 patients in the 6H arm and 3600 patients in the 3HP arm we will have 82% power to
      detect an increase in treatment completion of 5% (To -90%) in the 3HP arm. If treatment
      completion in the 6H arm is 75%, we will have approximately 90% power to detect an increase
      in treatment completion of 7% in the 3HP arm.

      Analysis: Treatment completion will be compared by study arm using Fishers Exact test, and
      associated risk difference and 95% confidence interval (CI).

      Part B: A randomised controlled trial of 3HP vs p3HP [enrollment starts concurrently with
      Part A]

      Justification: A single round of 3HP has been shown to be non-inferior to 9 months of
      isoniazid (9H) in persons at high risk of developing TB in low and middle TB burden settings.
      Similarly, a single round of 3HP has demonstrated similar efficacy in preventing active TB
      when compared to 6H among HIV-positive, tuberculin skin test (TST)-positive adults in the
      high burden setting of South Africa. In high burden settings, 6H and 3HP provide protection
      of limited duration probably due to high ongoing transmission and reinfection. Continuous
      isoniazid preventive therapy has been shown to provide more durable protection in high burden
      settings, but is not currently policy outside of a handful of countries, and the actual
      uptake is poor. Giving 3HP periodically may provide durable protection, be easier for health
      systems to implement, and may be associated with better adherence and fewer side effects.

      Sample size: Assuming a cumulative TB incidence of 5% over 2 years in the control (3HP) arm,
      an overall loss to follow-up of 10% by year 2, a two-sided type I error of 5%, 1:1
      randomisation, a superiority comparison and 1800 participants per arm, we have 80% power to
      detect a 40% reduction in cumulative TB incidence from months 0 to 24.

      Analysis: The analysis will compare 3HP and p3HP with two years of follow up. Cumulative TB
      incidence will be determined by combining incident TB cases identified over the 24 months of
      follow up AND prevalent TB cases identified at the 12 and 24 month culture survey. Data will
      be reported as a risk difference and odds ratio and their associated 95% CIs, adjusting for
      randomisation strata. The secondary outcome comparing the effectiveness of p3HP to 3HP from
      month 13 to 24 (during which time the greatest effect is likely to be evident) will be
      conducting using the same analytic methods. The results of Part B will be disseminated
      subsequent to the results of Part A.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Treatment completion (part A)
time frame: 1 year
description: Number of participants without evidence of active TB at enrollment who complete treatment, defined as:
Proportion of participants in 3HP group self-reporting treatment completion of ≥11 doses in a 16-week period
; Proportion or participants in 6H group self-reporting treatment completion of ≥167 doses over an 34 week (8-month) period
measure: TB incidence (part B)
time frame: 2 years
description: Number of participants without evidence of active TB at enrollment who are diagnosed with active TB meeting the definition: Confirmed tuberculosis: Culture-positive, Xpert MTB/RIF-positive, or smear-positive for M. tuberculosis from any site in adults and children OR Clinical tuberculosis: Started on treatment for TB in adults and children
measure: TB incidence (part A)
time frame: 1 year
description: Number of participants without evidence of active TB at enrollment who are diagnosed with active TB meeting the definition: Confirmed tuberculosis: Culture-positive, Xpert MTB/RIF-positive, or smear-positive for M. tuberculosis from any site in adults and children OR Clinical tuberculosis: Started on treatment for TB in adults and children
measure: All-cause mortality (part A)
time frame: 1 year
description: Number of participants without evidence of active TB at enrollment who die from any cause
measure: Permanent discontinuation of therapy due to treatment-related adverse events (part A)
time frame: 1 year
description: Number of participants without evidence of active TB at enrollment who permanently discontinue therapy due to an adverse drug reaction
measure: TB incidence (part B)
time frame: 1 year
description: Number of participants without evidence of active TB during enrollment who are diagnosed with active TB meeting during the second year of follow-up. The definition of active TB is: Confirmed tuberculosis: Culture-positive, Xpert MTB/RIF-positive, or smear-positive for M. tuberculosis from any site in adults and children OR Clinical tuberculosis: Started on treatment for TB in adults and children
measure: Treatment completion (part B)
time frame: 2 years
description: Number of participants without evidence of active TB at enrollment who complete treatment, defined as: Proportion of participants in 3HP group self-reporting treatment completion of ≥11 doses in a 16-week period; Proportion or participants in p3HP group self-reporting treatment completion of ≥22 doses over two annual 16-week periods
measure: All-cause mortality (part B)
time frame: 2 years
description: Number of participants without evidence of active TB at enrollment who die from any cause
measure: Permanent discontinuation of therapy due to treatment-related adverse events (part B)
time frame: 2 years
description: Number of participants without evidence of active TB at enrollment who permanently discontinue therapy due to an adverse drug reaction
measure: Cost per TB case prevented
time frame: 2 years
description: Cost per TB case prevented
measure: Cost per death averted
time frame: 2 years
description: Cost per death averted
measure: Cost per disability adjusted life year (DALY) averted by study arm
time frame: 2 years
description: Cost per disability adjusted life year (DALY) averted by study arm
measure: IGRA conversions (part A)
time frame: 1 year
description: Number of IGRA-negative participants without evidence of active TB at enrollment with the occurrence of IGRA conversions at the end of year 1
measure: IGRA reversions (part A)
time frame: 1 year
description: Number of IGRA-positive participants without evidence of active TB at enrollment with the occurrence of IGRA reversions at the end of year 1
measure: Incidence of TB resistant to isoniazid and/or rifapentine
time frame: 2 years
description: Number of individuals without evidence of active TB at enrollment who are diagnosed with active TB resistant to isoniazid and/or rifapentine
arm group label: 3HP (rifapentine + isoniazid)
arm group type: Active Comparator
description: Once weekly rifapentine (at a dose of 900 mg) plus isoniazid (at a dose of 900 mg), (with adjustment for participants weighing ≤50 kg) given for 12 weeks in Study Year 1
arm group label: p3HP (rifapentine + isoniazid)
arm group type: Active Comparator
description: Once weekly rifapentine (at a dose of 900 mg) plus isoniazid (at a dose of 900 mg), (with adjustment for participants weighing ≤50 kg) given for 12 weeks in Study Years 1 and 2
arm group label: 6H
arm group type: Active Comparator
description: Daily self-administered isoniazid (at a dose of 300 mg/daily) (with adjustment for participants weighing ≤24 kg) given for 26 weeks (6 months) in Study Year 1
intervention type: Drug
intervention name: rifapentine + isoniazid
description: Rifapentine + isoniazid Once weekly rifapentine (at a dose of 900 mg) plus isoniazid (at a dose of 900 mg), with adjustment for participants weighing ≤50 kg
arm group label: 3HP (rifapentine + isoniazid)
arm group label: p3HP (rifapentine + isoniazid)
other name: Priftin (rifapentine)
intervention type: Drug
intervention name: Isoniazid
description: Daily self-administered isoniazid (at a dose of 300 mg/daily), with adjustment for participants weighing ≤24 kg
arm group label: 6H
other name: Winthrop (isoniazid)
criteria: 
gender: All
minimum age: 2 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Gavin Churchyard, MBBCh, PhD
role: Principal Investigator
affiliation: Aurum Institute
facility: 
country: South Africa
citation: Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, Hackman J, Hamilton CD, Menzies D, Kerrigan A, Weis SE, Weiner M, Wing D, Conde MB, Bozeman L, Horsburgh CR Jr, Chaisson RE; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011 Dec 8;365(23):2155-66. doi: 10.1056/NEJMoa1104875.
PMID: 22150035
citation: Sterling TR, Moro RN, Borisov AS, Phillips E, Shepherd G, Adkinson NF, Weis S, Ho C, Villarino ME; Tuberculosis Trials Consortium. Flu-like and Other Systemic Drug Reactions Among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study. Clin Infect Dis. 2015 Aug 15;61(4):527-35. doi: 10.1093/cid/civ323. Epub 2015 Apr 22.
PMID: 25904367
citation: Sterling TR, Benson CA, Shang N. Tolerability among HIV-infected persons of three months of once-weekly rifapentine + INH (3HP) vs. 9 months of daily INH (9H) for treatment of latent tuberculosis infection. In: International AIDS Society Conference. Washington, DC.; 2012.
citation: Martinson NA, Barnes GL, Moulton LH, Msandiwa R, Hausler H, Ram M, McIntyre JA, Gray GE, Chaisson RE. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011 Jul 7;365(1):11-20. doi: 10.1056/NEJMoa1005136.
PMID: 21732833
citation: Villarino ME, Scott NA, Weis SE, Weiner M, Conde MB, Jones B, Nachman S, Oliveira R, Moro RN, Shang N, Goldberg SV, Sterling TR; International Maternal Pediatric and Adolescents AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr. 2015 Mar;169(3):247-55. doi: 10.1001/jamapediatrics.2014.3158. Erratum In: JAMA Pediatr. 2015 Sep;169(9):878.
PMID: 25580725
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Isoniazid
mesh term: Rifapentine
mesh term: Rifampin
sharing ipd: Undecided