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

15 czerwca 2026 zaktualizowane przez: 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.

Przegląd badań

Status

Jeszcze nie rekrutacja

Warunki

Interwencja / Leczenie

Szczegółowy opis

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 studiów

Interwencyjne

Zapisy (Szacowany)

230

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Lokalizacje studiów

  • Peru
      • Lima, Peru
        • Socios en Salud Sucursal Peru
        • Główny śledczy:
          • Leonid Lecca, MD

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dziecko

Akceptuje zdrowych ochotników

Nie

Opis

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 studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Arm 1: 8 week duration
N = 40, 8 weeks of odRHZE
Lek: 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
Inne nazwy:
  • two optimized-doses (odR) rifampicin
Lek: Isoniazid
50 mg tablet, dosed by weight and age
Inne nazwy:
  • Isoniazid (H)
Lek: Pyrazinamide
150 mg tablet, dosed by weight and age
Inne nazwy:
  • Pyrazinamide (Z)
Lek: Ethambutol
100 mg tablet, dosed by weight and age
Inne nazwy:
  • Ethambutol (E)
Lek: Rifampicin
standard of care and only the 75 mg tablet will be used
Inne nazwy:
  • standard dose rifampicin (R)
Eksperymentalny: Arm 2: 11 week duration
N = 40, 8 weeks of odRHZE followed by 3 weeks of odRH
Lek: 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
Inne nazwy:
  • two optimized-doses (odR) rifampicin
Lek: Isoniazid
50 mg tablet, dosed by weight and age
Inne nazwy:
  • Isoniazid (H)
Lek: Pyrazinamide
150 mg tablet, dosed by weight and age
Inne nazwy:
  • Pyrazinamide (Z)
Lek: Ethambutol
100 mg tablet, dosed by weight and age
Inne nazwy:
  • Ethambutol (E)
Lek: Rifampicin
standard of care and only the 75 mg tablet will be used
Inne nazwy:
  • standard dose rifampicin (R)
Eksperymentalny: Arm 3: 14 week duration
N = 40, 8 weeks of odRHZE followed by 6 weeks of odRH
Lek: 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
Inne nazwy:
  • two optimized-doses (odR) rifampicin
Lek: Isoniazid
50 mg tablet, dosed by weight and age
Inne nazwy:
  • Isoniazid (H)
Lek: Pyrazinamide
150 mg tablet, dosed by weight and age
Inne nazwy:
  • Pyrazinamide (Z)
Lek: Ethambutol
100 mg tablet, dosed by weight and age
Inne nazwy:
  • Ethambutol (E)
Lek: Rifampicin
standard of care and only the 75 mg tablet will be used
Inne nazwy:
  • standard dose rifampicin (R)
Eksperymentalny: Arm 4: 17 week duration
N = 40, 8 weeks of odRHZE followed by 9 weeks of odRH
Lek: 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
Inne nazwy:
  • two optimized-doses (odR) rifampicin
Lek: Isoniazid
50 mg tablet, dosed by weight and age
Inne nazwy:
  • Isoniazid (H)
Lek: Pyrazinamide
150 mg tablet, dosed by weight and age
Inne nazwy:
  • Pyrazinamide (Z)
Lek: Ethambutol
100 mg tablet, dosed by weight and age
Inne nazwy:
  • Ethambutol (E)
Lek: Rifampicin
standard of care and only the 75 mg tablet will be used
Inne nazwy:
  • standard dose rifampicin (R)
Aktywny komparator: 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
Lek: 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
Inne nazwy:
  • two optimized-doses (odR) rifampicin
Lek: Isoniazid
50 mg tablet, dosed by weight and age
Inne nazwy:
  • Isoniazid (H)
Lek: Pyrazinamide
150 mg tablet, dosed by weight and age
Inne nazwy:
  • Pyrazinamide (Z)
Lek: Ethambutol
100 mg tablet, dosed by weight and age
Inne nazwy:
  • Ethambutol (E)
Lek: Rifampicin
standard of care and only the 75 mg tablet will be used
Inne nazwy:
  • standard dose rifampicin (R)
Eksperymentalny: 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)
Lek: 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
Inne nazwy:
  • two optimized-doses (odR) rifampicin
Lek: Isoniazid
50 mg tablet, dosed by weight and age
Inne nazwy:
  • Isoniazid (H)
Lek: Pyrazinamide
150 mg tablet, dosed by weight and age
Inne nazwy:
  • Pyrazinamide (Z)
Lek: Ethambutol
100 mg tablet, dosed by weight and age
Inne nazwy:
  • Ethambutol (E)
Lek: Rifampicin
standard of care and only the 75 mg tablet will be used
Inne nazwy:
  • standard dose rifampicin (R)
Eksperymentalny: 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)
Lek: 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
Inne nazwy:
  • two optimized-doses (odR) rifampicin
Lek: Isoniazid
50 mg tablet, dosed by weight and age
Inne nazwy:
  • Isoniazid (H)
Lek: Pyrazinamide
150 mg tablet, dosed by weight and age
Inne nazwy:
  • Pyrazinamide (Z)
Lek: Ethambutol
100 mg tablet, dosed by weight and age
Inne nazwy:
  • Ethambutol (E)
Lek: Rifampicin
standard of care and only the 75 mg tablet will be used
Inne nazwy:
  • standard dose rifampicin (R)

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Step 2: Unfavorable TB treatment outcome
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

University of Wisconsin, Madison

Współpracownicy

National Institute of Allergy and Infectious Diseases (NIAID)

Śledczy

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

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Szacowany)

1 września 2026

Zakończenie podstawowe (Szacowany)

1 września 2030

Ukończenie studiów (Szacowany)

1 września 2030

Daty rejestracji na studia

Pierwszy przesłany

15 maja 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

15 czerwca 2026

Pierwszy wysłany (Rzeczywisty)

18 czerwca 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

18 czerwca 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

15 czerwca 2026

Ostatnia weryfikacja

1 czerwca 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

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

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Typ informacji pomocniczych dotyczących udostępniania IPD

  • PROTOKÓŁ BADANIA
  • SOK ROŚLINNY
  • ICF

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

produkt wyprodukowany i wyeksportowany z USA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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