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

15. června 2026 aktualizováno: 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.

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

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

Typ studie

Intervenční

Zápis (Odhadovaný)

230

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

Studijní místa

  • Peru
      • Lima, Peru
        • Socios en Salud Sucursal Peru
        • Vrchní vyšetřovatel:
          • Leonid Lecca, MD

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dítě

Přijímá zdravé dobrovolníky

Ne

Popis

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)

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Arm 1: 8 week duration
N = 40, 8 weeks of odRHZE
Lék: 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
Ostatní jména:
  • two optimized-doses (odR) rifampicin
Lék: Isoniazid
50 mg tablet, dosed by weight and age
Ostatní jména:
  • Isoniazid (H)
Lék: Pyrazinamide
150 mg tablet, dosed by weight and age
Ostatní jména:
  • Pyrazinamide (Z)
Lék: Ethambutol
100 mg tablet, dosed by weight and age
Ostatní jména:
  • Ethambutol (E)
Lék: Rifampicin
standard of care and only the 75 mg tablet will be used
Ostatní jména:
  • standard dose rifampicin (R)
Experimentální: Arm 2: 11 week duration
N = 40, 8 weeks of odRHZE followed by 3 weeks of odRH
Lék: 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
Ostatní jména:
  • two optimized-doses (odR) rifampicin
Lék: Isoniazid
50 mg tablet, dosed by weight and age
Ostatní jména:
  • Isoniazid (H)
Lék: Pyrazinamide
150 mg tablet, dosed by weight and age
Ostatní jména:
  • Pyrazinamide (Z)
Lék: Ethambutol
100 mg tablet, dosed by weight and age
Ostatní jména:
  • Ethambutol (E)
Lék: Rifampicin
standard of care and only the 75 mg tablet will be used
Ostatní jména:
  • standard dose rifampicin (R)
Experimentální: Arm 3: 14 week duration
N = 40, 8 weeks of odRHZE followed by 6 weeks of odRH
Lék: 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
Ostatní jména:
  • two optimized-doses (odR) rifampicin
Lék: Isoniazid
50 mg tablet, dosed by weight and age
Ostatní jména:
  • Isoniazid (H)
Lék: Pyrazinamide
150 mg tablet, dosed by weight and age
Ostatní jména:
  • Pyrazinamide (Z)
Lék: Ethambutol
100 mg tablet, dosed by weight and age
Ostatní jména:
  • Ethambutol (E)
Lék: Rifampicin
standard of care and only the 75 mg tablet will be used
Ostatní jména:
  • standard dose rifampicin (R)
Experimentální: Arm 4: 17 week duration
N = 40, 8 weeks of odRHZE followed by 9 weeks of odRH
Lék: 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
Ostatní jména:
  • two optimized-doses (odR) rifampicin
Lék: Isoniazid
50 mg tablet, dosed by weight and age
Ostatní jména:
  • Isoniazid (H)
Lék: Pyrazinamide
150 mg tablet, dosed by weight and age
Ostatní jména:
  • Pyrazinamide (Z)
Lék: Ethambutol
100 mg tablet, dosed by weight and age
Ostatní jména:
  • Ethambutol (E)
Lék: Rifampicin
standard of care and only the 75 mg tablet will be used
Ostatní jména:
  • standard dose rifampicin (R)
Aktivní komparátor: 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
Lék: 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
Ostatní jména:
  • two optimized-doses (odR) rifampicin
Lék: Isoniazid
50 mg tablet, dosed by weight and age
Ostatní jména:
  • Isoniazid (H)
Lék: Pyrazinamide
150 mg tablet, dosed by weight and age
Ostatní jména:
  • Pyrazinamide (Z)
Lék: Ethambutol
100 mg tablet, dosed by weight and age
Ostatní jména:
  • Ethambutol (E)
Lék: Rifampicin
standard of care and only the 75 mg tablet will be used
Ostatní jména:
  • standard dose rifampicin (R)
Experimentální: 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)
Lék: 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
Ostatní jména:
  • two optimized-doses (odR) rifampicin
Lék: Isoniazid
50 mg tablet, dosed by weight and age
Ostatní jména:
  • Isoniazid (H)
Lék: Pyrazinamide
150 mg tablet, dosed by weight and age
Ostatní jména:
  • Pyrazinamide (Z)
Lék: Ethambutol
100 mg tablet, dosed by weight and age
Ostatní jména:
  • Ethambutol (E)
Lék: Rifampicin
standard of care and only the 75 mg tablet will be used
Ostatní jména:
  • standard dose rifampicin (R)
Experimentální: 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)
Lék: 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
Ostatní jména:
  • two optimized-doses (odR) rifampicin
Lék: Isoniazid
50 mg tablet, dosed by weight and age
Ostatní jména:
  • Isoniazid (H)
Lék: Pyrazinamide
150 mg tablet, dosed by weight and age
Ostatní jména:
  • Pyrazinamide (Z)
Lék: Ethambutol
100 mg tablet, dosed by weight and age
Ostatní jména:
  • Ethambutol (E)
Lék: Rifampicin
standard of care and only the 75 mg tablet will be used
Ostatní jména:
  • standard dose rifampicin (R)

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Step 2: Unfavorable TB treatment outcome
Časové okno: 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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
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
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

University of Wisconsin, Madison

Spolupracovníci

National Institute of Allergy and Infectious Diseases (NIAID)

Vyšetřovatelé

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

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

1. září 2026

Primární dokončení (Odhadovaný)

1. září 2030

Dokončení studie (Odhadovaný)

1. září 2030

Termíny zápisu do studia

První předloženo

15. května 2026

První předloženo, které splnilo kritéria kontroly kvality

15. června 2026

První zveřejněno (Aktuální)

18. června 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

18. června 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

15. června 2026

Naposledy ověřeno

1. června 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • 2026-0205
  • SMPH | Pediatrics - GPAM (Jiný identifikátor: UW Madison)
  • Protocol Version 2/10/26 (Jiný identifikátor: UW Madison)
  • 1U01AI192041-01 (Grant/smlouva NIH USA)

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Typ podpůrných informací pro sdílení IPD

  • PROTOKOL STUDY
  • MÍZA
  • ICF

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

produkt vyrobený a vyvážený z USA

Ne

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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Podmínky

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Místa

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