<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/NCT04485156</url>
  </required_header>
  <id_info>
    <org_study_id>Hi-DoRi-3</org_study_id>
    <nct_id>NCT04485156</nct_id>
  </id_info>
  <brief_title>Treatment Shortening of Drug-Sensitive Pulmonary Tuberculosis Using High Dose Rifampicin (Hi-DoRi-3)</brief_title>
  <acronym>Hi-DoRi-3</acronym>
  <official_title>Treatment Shortening of Drug-Sensitive Pulmonary Tuberculosis Using High Dose Rifampicin to 3 Months After Culture Conversion (Hi-DoRi-3): A Phase 3, Multicenter, Randomized, Open-label, Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chonnam National University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Medical Center, Seoul</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pusan National University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pusan National University Yangsan Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seoul National University Bundang Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>SMG-SNU Boramae Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Korean Institute of Tuberculosis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>International Tuberculosis Research Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Korean Center for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Seoul National University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of this study is to investigate the effectiveness and safety of the regimen&#xD;
      including high dose rifampicin for individualized duration (3 months after Culture&#xD;
      Conversion) for the treatment of drug-sensitive pulmonary tuberculosis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">September 2020</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">August 2025</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of unfavorable treatment outcomes between two arms</measure>
    <time_frame>Within 18 months of randomization</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to unfavorable treatment outcomes</measure>
    <time_frame>Within 18 months of randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to culture conversion on liquid media</measure>
    <time_frame>Censored at 2 months of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with treatment success</measure>
    <time_frame>At the end of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with relapse of same strain</measure>
    <time_frame>At the end of study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to relapse with same strain</measure>
    <time_frame>through study completion, 18months after randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of AEs grade 3 and above</measure>
    <time_frame>through study completion, 18months after randomization</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">926</enrollment>
  <condition>Tuberculosis, Pulmonary</condition>
  <arm_group>
    <arm_group_label>Arm 1 (Conventional treatment group)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Will be treated as recommended by Korean Guidelines For Tuberculosis as well as WHO guidelines (e.g. isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months followed by isoniazid, rifampicin, (and ethambutol)) Duration of the treatment&#xD;
- 6 months in total</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 (High-dose rifampicin group)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High-dose rifampicin, isoniazid, and pyrazinamide&#xD;
Rifampicin: 30mg/kg&#xD;
Isoniazid: 300mg/day&#xD;
Pyrazinamide: 1000mg/day (&lt;50kg), 1500mg/day (50-70kg), 2000mg /day (&gt;70kg), till culture conversion Duration of the treatment&#xD;
Till 12 weeks after culture conversion on liquid media</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High-dose rifampicin</intervention_name>
    <description>30mg/kg</description>
    <arm_group_label>Arm 2 (High-dose rifampicin group)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isoniazid</intervention_name>
    <description>300mg</description>
    <arm_group_label>Arm 1 (Conventional treatment group)</arm_group_label>
    <arm_group_label>Arm 2 (High-dose rifampicin group)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pyrazinamide</intervention_name>
    <description>20-30mg/kg</description>
    <arm_group_label>Arm 1 (Conventional treatment group)</arm_group_label>
    <arm_group_label>Arm 2 (High-dose rifampicin group)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ethambutol</intervention_name>
    <description>15-20mg/kg</description>
    <arm_group_label>Arm 1 (Conventional treatment group)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifampicin</intervention_name>
    <description>10mg/kg</description>
    <arm_group_label>Arm 1 (Conventional treatment group)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented positivity by sputum Xpert MTB/RIF assay&#xD;
&#xD;
          -  Administration of current tuberculosis therapy (if any) for no more than 7 days (≤7)&#xD;
             at the time of enrolment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Negative on Xpert MTB/RIF assay&#xD;
&#xD;
          -  Resistance to rifampicin as detected by an Xpert MTB/RIF assay&#xD;
&#xD;
          -  Known resistance to isoniazid, rifampicin, or pyrazinamide&#xD;
&#xD;
          -  HIV positive&#xD;
&#xD;
          -  Cancer patient on anti-cancer chemotherapy&#xD;
&#xD;
          -  Uncontrolled DM&#xD;
&#xD;
          -  Chronic hepatitis, liver cirrhosis&#xD;
&#xD;
          -  Any contraindications of drugs to be used&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>July 21, 2020</last_update_submitted>
  <last_update_submitted_qc>July 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tuberculosis</keyword>
  <keyword>Rifampicin</keyword>
  <keyword>Treatment</keyword>
  <keyword>Shortening</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rifampin</mesh_term>
    <mesh_term>Isoniazid</mesh_term>
    <mesh_term>Pyrazinamide</mesh_term>
    <mesh_term>Ethambutol</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/NCT04485156
org study id: Hi-DoRi-3
nct id: NCT04485156
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate the effectiveness and safety of the regimen
      including high dose rifampicin for individualized duration (3 months after Culture
      Conversion) for the treatment of drug-sensitive pulmonary tuberculosis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of unfavorable treatment outcomes between two arms
time frame: Within 18 months of randomization
measure: Time to unfavorable treatment outcomes
time frame: Within 18 months of randomization
measure: Time to culture conversion on liquid media
time frame: Censored at 2 months of treatment
measure: Proportion of participants with treatment success
time frame: At the end of treatment
measure: Proportion of participants with relapse of same strain
time frame: At the end of study
measure: Time to relapse with same strain
time frame: through study completion, 18months after randomization
measure: Occurrence of AEs grade 3 and above
time frame: through study completion, 18months after randomization
arm group label: Arm 1 (Conventional treatment group)
arm group type: Active Comparator
description: Will be treated as recommended by Korean Guidelines For Tuberculosis as well as WHO guidelines (e.g. isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months followed by isoniazid, rifampicin, (and ethambutol)) Duration of the treatment
- 6 months in total
arm group label: Arm 2 (High-dose rifampicin group)
arm group type: Experimental
description: High-dose rifampicin, isoniazid, and pyrazinamide
Rifampicin: 30mg/kg
Isoniazid: 300mg/day
Pyrazinamide: 1000mg/day (<50kg), 1500mg/day (50-70kg), 2000mg /day (>70kg), till culture conversion Duration of the treatment
Till 12 weeks after culture conversion on liquid media
intervention type: Drug
intervention name: High-dose rifampicin
description: 30mg/kg
arm group label: Arm 2 (High-dose rifampicin group)
intervention type: Drug
intervention name: Isoniazid
description: 300mg
arm group label: Arm 1 (Conventional treatment group)
arm group label: Arm 2 (High-dose rifampicin group)
intervention type: Drug
intervention name: Pyrazinamide
description: 20-30mg/kg
arm group label: Arm 1 (Conventional treatment group)
arm group label: Arm 2 (High-dose rifampicin group)
intervention type: Drug
intervention name: Ethambutol
description: 15-20mg/kg
arm group label: Arm 1 (Conventional treatment group)
intervention type: Drug
intervention name: Rifampicin
description: 10mg/kg
arm group label: Arm 1 (Conventional treatment group)
criteria: 
gender: All
minimum age: 19 Years
maximum age: 85 Years
healthy volunteers: No
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Tuberculosis, Pulmonary
mesh term: Rifampin
mesh term: Isoniazid
mesh term: Pyrazinamide
mesh term: Ethambutol
sharing ipd: Undecided