Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
RECRUITING
Clinical Phase
PHASE3
Total Enrollment
860 participants
Study Classification
INTERVENTIONAL
Study Start Date
2025-01-15
Study Completion Date
2027-09-30
Brief Summary
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While drug-susceptible tuberculosis (TB) disease in children currently requires four to six months of treatment, most children may be able to be cured with a shorter treatment of more powerful drugs. Shorter treatment may be easier for children to tolerate and finish as well as ease caregiver strain from managing treatment side effects and supporting children over many months. The primary objective of this study is to evaluate if a 2-month regimen (including isoniazid (H), rifapentine (P), pyrazinamide (Z) and moxifloxacin (M)) is as safe and effective as a 4- to 6-month regimen (isoniazid, rifampicin (R), pyrazinamide, ethambutol (E)) in curing drug-susceptible TB disease in children under 10 years old. The study is also evaluating the safety of the HPZM in children with and without HIV.
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Detailed Description
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In previously untreated individuals with presumed drug-susceptible pulmonary and or peripheral lymph node TB treated with eight weeks of rifapentine, isoniazid, pyrazinamide and moxifloxacin (2HPZM), all given daily throughout, the proportion of participants who experience absence of cure (unsuccessful outcome) will not be inferior to that observed in participants who are treated with the standard regimen (eight weeks of rifampin, isoniazid, pyrazinamide, with or without ethambutol followed by 8 to 16 weeks of rifampin plus isoniazid depending on disease severity) all given daily throughout.
Conditions
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Tuberculosis
Tuberculosis, Pulmonary
Tuberculosis, Lymph Node
Mycobacterium Tuberculosis
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
International, multicenter, randomized, controlled, open-label, non-inferiority
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Regimen 1: Isoniazid (H), Rifampin (R), Pyrazinamide (Z), Ethambutol (E)
8 weeks of daily HRZ(E) followed by either 16 or 24 weeks of daily HR, per local standard of care
Group Type
ACTIVE_COMPARATOR
Isoniazid
Intervention Type
DRUG
Once daily weight-based dose
Rifampin
Intervention Type
DRUG
Once daily weight-based dose
Pyrazinamide
Intervention Type
DRUG
Once daily weight-based dose
Ethambutol
Intervention Type
DRUG
Once daily weight-based dose
Regimen 2: Isoniazid (H), Rifapentine (P), Pyrazinamide (Z), Moxifloxacin (M)
8 weeks of daily HPZM
Group Type
EXPERIMENTAL
Isoniazid
Intervention Type
DRUG
Once daily weight-based dose
Pyrazinamide
Intervention Type
DRUG
Once daily weight-based dose
Rifapentine
Intervention Type
DRUG
Once daily weight-based dose
Moxifloxacin
Intervention Type
DRUG
Once daily weight-based dose
Interventions
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Isoniazid
Once daily weight-based dose
Intervention Type
DRUG
Rifampin
Once daily weight-based dose
Intervention Type
DRUG
Pyrazinamide
Once daily weight-based dose
Intervention Type
DRUG
Ethambutol
Once daily weight-based dose
Intervention Type
DRUG
Rifapentine
Once daily weight-based dose
Intervention Type
DRUG
Moxifloxacin
Once daily weight-based dose
Intervention Type
DRUG
Other Intervention Names
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H
R
Z
E
P
Priftin
M
Avelox
Eligibility Criteria
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Inclusion Criteria
* Parent or guardian is willing and able to provide written informed consent for potential participant's study participation; in addition, when applicable per Ethics Committee/Institutional Review Board (EC/IRB) policies and procedures, potential participant is willing and able to provide assent for study participation.
* At Entry, age of less than 10 years.
* At Entry, weight 3 kilograms (kg) or greater.
* At Entry, diagnosed with TB disease, defined as:
* Pulmonary (including pleural effusion) and/or lymph node (extra-thoracic and/or intra-thoracic) TB with or without bacteriologic confirmation;
* Clinician has decided to treat with standard first-line drug-susceptible TB regimen.
* Known HIV status or HIV testing in progress based on meeting testing requirements.
* Has normal, Grade 1 or 2 test results for all of the following done at or within 14 days of Entry (including the most recent):
* Alanine aminotransferase (ALT) less than or equal to 5 times the upper limit of normal;
* Total bilirubin less than or equal to 2.5 times the upper limit of normal;
* Potassium level of 3.0 milliequivalent/L or greater;
* Hemoglobin level of 7.0 g/dL or greater;
* Platelet count of 100,000/mm3 or greater;
* Estimated glomerular filtration rate (eGFR; bedside Schwartz formula) 60 mL/min/1.73m2 or higher.
* For children living with HIV:
* On antiretroviral therapy (ART) at Entry: Must be on, or able to be switched to a dolutegravir-based regimen at or prior to Entry;
* Not on ART at Entry: Planned initiation of dolutegravir before or at study Week 4.
* For participants who have reached menarche or who are engaging in sexual activity (self-reported): negative serum or urine pregnancy test within 7 days of Entry.
* For participants who are engaging in sexual activity that could lead to pregnancy (self-reported): agrees to practice at least one non-hormonal method of contraception or abstain from heterosexual intercourse during study drug treatment and for 30 days after stopping study medications. Non-hormonal methods include:
* Male or female condoms
* Diaphragm or cervical cap (with spermicide, if available)
* Non-hormonal intrauterine device (IUD) or intrauterine system (IUS)
* At Entry, intends to remain in the catchment area of the study site for the duration of study follow-up or willingness to be followed up beyond the catchment area if/when applicable, as determined by the site investigator based on participant/parent/guardian report.
* At Entry, age of less than 10 years.
* At Entry, weight 3 kilograms (kg) or greater.
* At Entry, diagnosed with TB disease, defined as:
* Pulmonary (including pleural effusion) and/or lymph node (extra-thoracic and/or intra-thoracic) TB with or without bacteriologic confirmation;
* Clinician has decided to treat with standard first-line drug-susceptible TB regimen.
* Known HIV status or HIV testing in progress based on meeting testing requirements.
* Has normal, Grade 1 or 2 test results for all of the following done at or within 14 days of Entry (including the most recent):
* Alanine aminotransferase (ALT) less than or equal to 5 times the upper limit of normal;
* Total bilirubin less than or equal to 2.5 times the upper limit of normal;
* Potassium level of 3.0 milliequivalent/L or greater;
* Hemoglobin level of 7.0 g/dL or greater;
* Platelet count of 100,000/mm3 or greater;
* Estimated glomerular filtration rate (eGFR; bedside Schwartz formula) 60 mL/min/1.73m2 or higher.
* For children living with HIV:
* On antiretroviral therapy (ART) at Entry: Must be on, or able to be switched to a dolutegravir-based regimen at or prior to Entry;
* Not on ART at Entry: Planned initiation of dolutegravir before or at study Week 4.
* For participants who have reached menarche or who are engaging in sexual activity (self-reported): negative serum or urine pregnancy test within 7 days of Entry.
* For participants who are engaging in sexual activity that could lead to pregnancy (self-reported): agrees to practice at least one non-hormonal method of contraception or abstain from heterosexual intercourse during study drug treatment and for 30 days after stopping study medications. Non-hormonal methods include:
* Male or female condoms
* Diaphragm or cervical cap (with spermicide, if available)
* Non-hormonal intrauterine device (IUD) or intrauterine system (IUS)
* At Entry, intends to remain in the catchment area of the study site for the duration of study follow-up or willingness to be followed up beyond the catchment area if/when applicable, as determined by the site investigator based on participant/parent/guardian report.
Exclusion Criteria
* Presumed or documented extra-pulmonary TB involving the central nervous system and/or bones and/or joints, and/or miliary TB, and/or pericardial TB and/or TB of the gastrointestinal (GI) tract and/or renal TB.
* Premature infant (born less than 37-weeks gestation) who is less than 3 months of age at Entry.
* Any known contraindication to taking any study drug:
* Known allergy or intolerance to any of the study drugs or drugs in the same class as the study drugs;
* Any prohibited medications within three days prior to Entry or planned use within the following 6 months;
* Unable to take oral medications;
* Known history of prolonged QT syndrome not caused by electrolyte derangements.
* Received more than 10 days of treatment directed against TB disease within 6 months preceding initiation of study drugs.
* M. tuberculosis isolate known or suspected to be resistant to isoniazid, rifampin, pyrazinamide, ethambutol, and/or fluoroquinolones.
* Known exposure to an infectious adult with drug-resistant TB, including resistance to isoniazid, rifampin, pyrazinamide, ethambutol, and/or fluoroquinolones.
* Has any other documented or suspected clinically significant medical condition or any other condition that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
* Previously enrolled in this study.
Late Exclusions:
* M. tuberculosis cultured or detected through World Health Organization (WHO) approved molecular assays (e.g., Cepheid Xpert MTB/RIF, Xpert XDR, sequencing or Hain MTB-DR plus assays) from sputum, swallowed sputum, nasopharyngeal aspirates, stool, or lymph node aspirate obtained around the time of study entry is determined to be resistant to isoniazid and/or rifampin and/or pyrazinamide and/or ethambutol and/or fluoroquinolones.
* Any child with a clinical TB diagnosis who is found to have a definitive alternative diagnosis for their presenting signs and symptoms whose TB treatment is discontinued prior to completion.
* Premature infant (born less than 37-weeks gestation) who is less than 3 months of age at Entry.
* Any known contraindication to taking any study drug:
* Known allergy or intolerance to any of the study drugs or drugs in the same class as the study drugs;
* Any prohibited medications within three days prior to Entry or planned use within the following 6 months;
* Unable to take oral medications;
* Known history of prolonged QT syndrome not caused by electrolyte derangements.
* Received more than 10 days of treatment directed against TB disease within 6 months preceding initiation of study drugs.
* M. tuberculosis isolate known or suspected to be resistant to isoniazid, rifampin, pyrazinamide, ethambutol, and/or fluoroquinolones.
* Known exposure to an infectious adult with drug-resistant TB, including resistance to isoniazid, rifampin, pyrazinamide, ethambutol, and/or fluoroquinolones.
* Has any other documented or suspected clinically significant medical condition or any other condition that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
* Previously enrolled in this study.
Late Exclusions:
* M. tuberculosis cultured or detected through World Health Organization (WHO) approved molecular assays (e.g., Cepheid Xpert MTB/RIF, Xpert XDR, sequencing or Hain MTB-DR plus assays) from sputum, swallowed sputum, nasopharyngeal aspirates, stool, or lymph node aspirate obtained around the time of study entry is determined to be resistant to isoniazid and/or rifampin and/or pyrazinamide and/or ethambutol and/or fluoroquinolones.
* Any child with a clinical TB diagnosis who is found to have a definitive alternative diagnosis for their presenting signs and symptoms whose TB treatment is discontinued prior to completion.
Minimum Eligible Age
0 Days
Maximum Eligible Age
9 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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United States Agency for International Development (USAID)
FED
Sponsor Role
collaborator
Johns Hopkins University
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Nicole Salazar-Austin, MD, ScM
Role: PRINCIPAL_INVESTIGATOR
Johns Hopkins University
Locations
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Indian Council of Medical Research - National Institute for Research in Tuberculosis
Chennai, , India
Site Status
NOT_YET_RECRUITING
Dr. D.Y. Patil Medical College, Hospital and Research Center
Pune, , India
Site Status
NOT_YET_RECRUITING
Faculty of Medicine, Universitas Padjadjaran
Bandung, , Indonesia
Site Status
RECRUITING
Instituto Nacional de Saúde (INS)
Maputo, , Mozambique
Site Status
NOT_YET_RECRUITING
Africa Health Research Institute (AHRI)
Durban, , South Africa
Site Status
NOT_YET_RECRUITING
MU-JHU Care Ltd
Kampala, , Uganda
Site Status
RECRUITING
University of Zambia, School of Medicine
Lusaka, , Zambia
Site Status
RECRUITING
Arthur Davison Children's Hospital
Ndola, , Zambia
Site Status
NOT_YET_RECRUITING
Harare Health and Research Consortium (HHRC)
Harare, , Zimbabwe
Site Status
NOT_YET_RECRUITING
Countries
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India
Indonesia
Mozambique
South Africa
Uganda
Zambia
Zimbabwe
Central Contacts
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Facility Contacts
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Aishwarya Venkataraman, MBBS, DCH, PgDip PID, MRCPCH
Role: primary
+44 2836 9500 ext. 9533
Role: backup
References
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Dorman SE, Goldberg S, Stout JE, Muzanyi G, Johnson JL, Weiner M, Bozeman L, Heilig CM, Feng PJ, Moro R, Narita M, Nahid P, Ray S, Bates E, Haile B, Nuermberger EL, Vernon A, Schluger NW; Tuberculosis Trials Consortium. Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: study 29 of the tuberculosis trials consortium. J Infect Dis. 2012 Oct 1;206(7):1030-40. doi: 10.1093/infdis/jis461. Epub 2012 Jul 30.
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Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
IRB00388853
Identifier Type: -
Identifier Source: org_study_id
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