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Re-evaluating the Duration in Children of TB Treatment (REDUCE TB)

15 juin 2026 mis à jour par: University of Wisconsin, Madison

Multi-arm, Open-label, Duration-randomized, Phase IIc Study of the Efficacy, Safety, Tolerability, and Pharmacokinetics of Optimized Rifampicin in Combination With Isoniazid, Pyrazinamide, and Ethambutol for the Treatment of Children With Drug-susceptible Tuberculosis

Current tuberculosis (TB) treatment is effective (works well), but it takes a long time to cure TB. This study will evaluate if TB treatment with a higher dose of rifampicin, one of the TB medicines, and shorter TB treatment duration is as effective and safe as the standard, TB treatment (with the usual rifampicin dose and usual duration). This study hopes to find a better shorter treatment that works as well as the current treatment (standard of care). This could benefit children worldwide who are getting TB treatment.

Children 3 months to less than 10 years of age who have drug-susceptible TB (can be successfully treated with standard TB medicines) are eligible for this study.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Description détaillée

This is a multi-arm open-label phase IIc trial with duration randomization, with a lead-in pharmacokinetics (PK) study. Children 3 months to less than 10 years of age with routinely diagnosed clinical or confirmed drug-susceptible TB will be screened and if eligible randomly assigned 1:1:1:1:1 to one of five arms (durations of TB treatment and control arm). Randomization will be stratified by age (3 months to less than 5 years of age vs 5 to less than 10 years of age).

A total of 200 participants will be enrolled in the main trial (Step 2), with 40 per study arm, with an additional 30 participants enrolled in a Lead-in PK study (Step 1).

Step 1 - Lead-in PK study participants will be on treatment for 8 weeks, complete their trial participation in up to 9 weeks, and will not contribute to the main trial endpoints.

Step 2 - Main trial participants will be on study for 48 weeks.

Primary Objective:

In children with drug-susceptible tuberculosis, with and without HIV:

• To characterize the relationship between treatment duration of the experimental regimen and the proportion of participants with unfavorable treatment outcome at 48 weeks after randomization (i.e., the duration-response curve)

Secondary Objectives:

The secondary objectives of the Lead-In PK study are to

  • Characterize the safety and tolerability of two optimized doses of rifampicin with standard doses of isoniazid, pyrazinamide and ethambutol
  • Characterize the pharmacokinetics of two optimized doses of rifampicin
  • Characterize the acceptability of two optimized doses of rifampicin

The secondary objectives of the Main Study are to:

  • Characterize the safety and tolerability of optimized-dose rifampicin with standard doses of isoniazid, pyrazinamide and ethambutol
  • Characterize the pharmacokinetics of optimized-dose rifampicin
  • Characterize lung health post-TB treatment at week 48 among children able to complete lung-health assessments
  • Characterize the acceptability of optimized-dose rifampicin

Type d'étude

Interventionnel

Inscription (Estimé)

230

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • Pérou
      • Lima, Pérou
        • Socios en Salud Sucursal Peru
        • Chercheur principal:
          • Leonid Lecca, MD

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Enfant

Accepte les volontaires sains

Non

La description

Inclusion Criteria:

  • 3 months to less than 10 years of age
  • Body weight greater than or equal to 3 kilograms (kg) and less than 45 kg at study entry

  • Confirmed or clinically diagnosed intrathoracic (pulmonary) and/or some forms of extrathoracic (extrapulmonary) drug-susceptible TB:

    • Confirmed intrathoracic (pulmonary) TB, based on chest radiograph and/or symptoms consistent with TB, and/or some forms of extrathoracic TB, with all of the following as determined by the site investigator:

      • Microbiological confirmation of M. tuberculosis from any clinical specimen by either culture or molecular methods
      • At least rifampicin-susceptibility demonstrated by genotypic (molecular) or phenotypic methods
      • Documented clinical decision to treat for drug-susceptible TB

    • Clinically diagnosed intrathoracic (pulmonary) TB, based on chest radiograph and/or symptoms consistent with TB, and/or some forms of extrathoracic TB, with all of the following as determined by the site investigator:

      • Documented clinical decision to treat for drug-susceptible TB
  • HIV positive or negative
  • For participants living with HIV, they must be on a dolutegravir-based antiretroviral therapy regimen at the time of study entry

Exclusion Criteria:

  • Received routine treatment for TB disease for greater than 5 days at the time of enrollment
  • Exposure to a case of intrathoracic TB in the 12 months prior to enrollment with known or suspected resistance to any of the drugs in the treatment regimens OR confirmed resistance on molecular or phenotypic drug-susceptibility testing to any drugs in the treatment regimens
  • Has greater than or equal to grade 3 results of any of the following during screening: creatinine, serum ALT, AST, total bilirubin
  • Has hemoglobin less than 7.5 g/dL during screening
  • Has TB meningitis, osteoarticular TB, or miliary TB as determined by the site investigator
  • Severe renal, pulmonary, cardiac, gastrointestinal, neurologic or any other condition that in the judgement of the investigator would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives
  • Use of any prohibited drug within 3 days of enrollment
  • Severe acute malnutrition defined as weight-for-height/length z-score or BMI-for-age z-score less than -3
  • Hypersensitivity to any of the study drugs (rifampicin, isoniazid, pyrazinamide or ethambutol)
  • For Main Trial (Step 2) participants, previously enrolled in the Lead-in PK Study (Step 1)

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Arm 1: 8 week duration
N = 40, 8 weeks of odRHZE
Médicament: Rifampicin
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
Autres noms:
  • two optimized-doses (odR) rifampicin
Médicament: Isoniazid
50 mg tablet, dosed by weight and age
Autres noms:
  • Isoniazid (H)
Médicament: Pyrazinamide
150 mg tablet, dosed by weight and age
Autres noms:
  • Pyrazinamide (Z)
Médicament: Ethambutol
100 mg tablet, dosed by weight and age
Autres noms:
  • Ethambutol (E)
Médicament: Rifampicin
standard of care and only the 75 mg tablet will be used
Autres noms:
  • standard dose rifampicin (R)
Expérimental: Arm 2: 11 week duration
N = 40, 8 weeks of odRHZE followed by 3 weeks of odRH
Médicament: Rifampicin
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
Autres noms:
  • two optimized-doses (odR) rifampicin
Médicament: Isoniazid
50 mg tablet, dosed by weight and age
Autres noms:
  • Isoniazid (H)
Médicament: Pyrazinamide
150 mg tablet, dosed by weight and age
Autres noms:
  • Pyrazinamide (Z)
Médicament: Ethambutol
100 mg tablet, dosed by weight and age
Autres noms:
  • Ethambutol (E)
Médicament: Rifampicin
standard of care and only the 75 mg tablet will be used
Autres noms:
  • standard dose rifampicin (R)
Expérimental: Arm 3: 14 week duration
N = 40, 8 weeks of odRHZE followed by 6 weeks of odRH
Médicament: Rifampicin
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
Autres noms:
  • two optimized-doses (odR) rifampicin
Médicament: Isoniazid
50 mg tablet, dosed by weight and age
Autres noms:
  • Isoniazid (H)
Médicament: Pyrazinamide
150 mg tablet, dosed by weight and age
Autres noms:
  • Pyrazinamide (Z)
Médicament: Ethambutol
100 mg tablet, dosed by weight and age
Autres noms:
  • Ethambutol (E)
Médicament: Rifampicin
standard of care and only the 75 mg tablet will be used
Autres noms:
  • standard dose rifampicin (R)
Expérimental: Arm 4: 17 week duration
N = 40, 8 weeks of odRHZE followed by 9 weeks of odRH
Médicament: Rifampicin
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
Autres noms:
  • two optimized-doses (odR) rifampicin
Médicament: Isoniazid
50 mg tablet, dosed by weight and age
Autres noms:
  • Isoniazid (H)
Médicament: Pyrazinamide
150 mg tablet, dosed by weight and age
Autres noms:
  • Pyrazinamide (Z)
Médicament: Ethambutol
100 mg tablet, dosed by weight and age
Autres noms:
  • Ethambutol (E)
Médicament: Rifampicin
standard of care and only the 75 mg tablet will be used
Autres noms:
  • standard dose rifampicin (R)
Comparateur actif: Arm 5: Control (17 or 24 week duration)
N = 40, 8 week of RHZ(E) followed by 9 weeks (5a - non-severe TB) or 16 weeks (5b - severe TB) of RH
Médicament: Rifampicin
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
Autres noms:
  • two optimized-doses (odR) rifampicin
Médicament: Isoniazid
50 mg tablet, dosed by weight and age
Autres noms:
  • Isoniazid (H)
Médicament: Pyrazinamide
150 mg tablet, dosed by weight and age
Autres noms:
  • Pyrazinamide (Z)
Médicament: Ethambutol
100 mg tablet, dosed by weight and age
Autres noms:
  • Ethambutol (E)
Médicament: Rifampicin
standard of care and only the 75 mg tablet will be used
Autres noms:
  • standard dose rifampicin (R)
Expérimental: Step 1: PK - Dosing Schedule A > B

N = 15

  • Period 1 - odRIF Dosing Schedule A with HZE, PK sampling after 4 weeks followed by
  • Period 2 - odRIF Dosing Schedule B with HZE, PK sampling after 4 weeks

Dosing schedules are by weight and age, with Schedule A a higher dose of RIF (totaling 250 - 1650mg) than Schedule B (totaling 200 - 1350mg)
Médicament: Rifampicin
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
Autres noms:
  • two optimized-doses (odR) rifampicin
Médicament: Isoniazid
50 mg tablet, dosed by weight and age
Autres noms:
  • Isoniazid (H)
Médicament: Pyrazinamide
150 mg tablet, dosed by weight and age
Autres noms:
  • Pyrazinamide (Z)
Médicament: Ethambutol
100 mg tablet, dosed by weight and age
Autres noms:
  • Ethambutol (E)
Médicament: Rifampicin
standard of care and only the 75 mg tablet will be used
Autres noms:
  • standard dose rifampicin (R)
Expérimental: Step 1: PK - Dosing Schedule B > A

N = 15

  • Period 1 - odRIF Dosing Schedule B with HZE, PK sampling after 4 weeks followed by
  • Period 2 - odRIF Dosing Schedule A with HZE, PK sampling after 4 weeks

Dosing schedules are by weight and age, with Schedule A a higher dose of RIF (totaling 250 - 1650mg) than Schedule B (totaling 200 - 1350mg)
Médicament: Rifampicin
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
Autres noms:
  • two optimized-doses (odR) rifampicin
Médicament: Isoniazid
50 mg tablet, dosed by weight and age
Autres noms:
  • Isoniazid (H)
Médicament: Pyrazinamide
150 mg tablet, dosed by weight and age
Autres noms:
  • Pyrazinamide (Z)
Médicament: Ethambutol
100 mg tablet, dosed by weight and age
Autres noms:
  • Ethambutol (E)
Médicament: Rifampicin
standard of care and only the 75 mg tablet will be used
Autres noms:
  • standard dose rifampicin (R)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Step 2: Unfavorable TB treatment outcome
Délai: 48 weeks

A participant has unfavorable treatment outcomes if they fail to meet either of the following criteria:

  • No treatment extension or re-treatment for TB at any time up through 48 weeks after randomization.
  • TB recurrence-free cure or Probable TB recurrence-free cure
48 weeks

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Step 1: Safety measured by occurrence of Grade 3 to 5 Adverse Events after the first dose of study treatment by period in Lead-in PK study
Délai: data collected from individual participants for 2 regimens of 4 weeks each, up to 8 weeks total
Occurrence of at least one new or worsened Grade 3-5 Adverse Event (AE) after the first dose of study treatment by period.
data collected from individual participants for 2 regimens of 4 weeks each, up to 8 weeks total
Step 1: Tolerability Measured by discontinuation of at least one drug in Lead-in PK study
Délai: data collected from individual participants for 2 regimens of 4 weeks each, up to 8 weeks total
Permanent discontinuation of at least one drug in the study regimen during each treatment period due to an AE of any grade that is either safety- or tolerability-related, death due to toxicity (probably/possibly/certainly) related to one or more of the study drugs, or participant/parent/guardian request.
data collected from individual participants for 2 regimens of 4 weeks each, up to 8 weeks total
Step 1: Pharmacokinetics of optimized-dose rifampicin: (AUC0-24)
Délai: data collected at week 4 (and week 8) visit lead-in PK study; pre-dose (0 hour), 1, 2, 4, 8 and 24 hour post dose
Area under the concentration time curve over 24 hours (AUC0-24)
data collected at week 4 (and week 8) visit lead-in PK study; pre-dose (0 hour), 1, 2, 4, 8 and 24 hour post dose
Step 1: Pharmacokinetics of optimized-dose rifampicin: (Cmax)
Délai: data collected at week 4 (and week 8) visit lead-in PK study; pre-dose (0 hour), 1, 2, 4, 8 and 24 hour post dose
Maximum concentration (Cmax)
data collected at week 4 (and week 8) visit lead-in PK study; pre-dose (0 hour), 1, 2, 4, 8 and 24 hour post dose
Step 1: Acceptability of optimized-dose rifampicin summarized by participant count
Délai: baseline (at dose 1), week 4, week 8
Participant and/or parent/guardian responses to rifampicin acceptability question of "Overall, how did you/your child feel about taking this medicine?", scored on a likert scale from 1-5 with higher scores being more acceptable. Summarized by number of responses per score.
baseline (at dose 1), week 4, week 8
Step 2: Safety Measured by Occurrence of at least one new or worsened Grade 3-5 adverse event after the first dose of study treatment in Main Trial
Délai: up to 28 weeks
Occurrence of at least one new or worsened Grade 3-5 adverse event after the first dose of study treatment and during the 28 weeks following randomization, where 28 weeks is 4 weeks beyond the longest scheduled treatment duration of 24 weeks.
up to 28 weeks
Step 2: Tolerability Measured by discontinuation of at least one drug in Main Trial
Délai: up to 24 weeks
Permanent discontinuation of at least one drug in the study regimen prior to the end of the assigned treatment period due to an AE of any grade that is either safety- or tolerability-related, death due to toxicity (probably/possibly/certainly) related to one or more of the study drugs, or participant/parent/guardian request.
up to 24 weeks
Step 2: Lung function post-TB treatment
Délai: week 48

The outcome of interest is abnormal lung function classified as having at least one of the following physiological findings based on results of spirometry and oscillometry (FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity):

  • Obstructive lung disease: defined as FEV1, or FEV1/FVC of <-1.64 z-score (z-score<-1.64 = lower limit of normal, LLN) with normal FVC
  • Restrictive lung disease: defined as FVC <-1.64 z-score with normal FEV1
  • Mixed lung disease: defined as FEV1/FVC <LLN;
  • Isolated small airway dysfunction: defined as oscillometry Area of reactance (AX) >1.64 z-score and/or oscillometry peripheral airway resistance (R5-20) >1.64 z-score with normal FEV1 on spirometry
week 48
Step 2: Acceptability of optimized-dose rifampicin summarized by participant count
Délai: baseline (at dose 1), week 4, week 8
Participant and/or parent/guardian responses to rifampicin acceptability question of "Overall, how did you/your child feel about taking this medicine?", scored on a likert scale from 1-5 with higher scores being more acceptable. Summarized by number of responses per score.
baseline (at dose 1), week 4, week 8
Step 2: Acceptability of overall TB treatment regimen summarized by participant count
Délai: week 4, week 8
Participant and/or parent/guardian responses to overall TB treatment regimen acceptability question of "In the last 4 weeks, how did you/your child feel about taking this TB treatment regimen, considering all of the TB medicines in the regimen together?", scored on a likert scale from 1-5 with higher scores being more acceptable. Summarized by number of responses per score.
week 4, week 8

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

University of Wisconsin, Madison

Collaborateurs

National Institute of Allergy and Infectious Diseases (NIAID)

Les enquêteurs

  • Chercheur principal: Anthony Garcia-Prats, MD, MSc, PhD, UW School of Medicine and Public Health

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 septembre 2026

Achèvement primaire (Estimé)

1 septembre 2030

Achèvement de l'étude (Estimé)

1 septembre 2030

Dates d'inscription aux études

Première soumission

15 mai 2026

Première soumission répondant aux critères de contrôle qualité

15 juin 2026

Première publication (Réel)

18 juin 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

18 juin 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

15 juin 2026

Dernière vérification

1 juin 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 2026-0205
  • SMPH | Pediatrics - GPAM (Autre identifiant: UW Madison)
  • Protocol Version 2/10/26 (Autre identifiant: UW Madison)
  • 1U01AI192041-01 (Subvention/contrat des NIH des États-Unis)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE
  • SÈVE
  • CIF

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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