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

15 июня 2026 г. обновлено: 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.

Обзор исследования

Статус

Еще не набирают

Условия

Вмешательство/лечение

Подробное описание

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

Тип исследования

Интервенционный

Регистрация (Оцененный)

230

Фаза

  • Фаза 2

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Контакты исследования

  • Имя: UW Clinical Trials Institute
  • Номер телефона: 608.265.3132
  • Электронная почта: info@clinicaltrials.wisc.edu

Места учебы

  • Перу
      • Lima, Перу
        • Socios en Salud Sucursal Peru
        • Главный следователь:
          • Leonid Lecca, MD

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

  • Ребенок

Принимает здоровых добровольцев

Нет

Описание

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)

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Нет (открытая этикетка)

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: Arm 1: 8 week duration
N = 40, 8 weeks of odRHZE
Лекарство: 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
Другие имена:
  • two optimized-doses (odR) rifampicin
Лекарство: Isoniazid
50 mg tablet, dosed by weight and age
Другие имена:
  • Isoniazid (H)
Лекарство: Pyrazinamide
150 mg tablet, dosed by weight and age
Другие имена:
  • Pyrazinamide (Z)
Лекарство: Ethambutol
100 mg tablet, dosed by weight and age
Другие имена:
  • Ethambutol (E)
Лекарство: Rifampicin
standard of care and only the 75 mg tablet will be used
Другие имена:
  • standard dose rifampicin (R)
Экспериментальный: Arm 2: 11 week duration
N = 40, 8 weeks of odRHZE followed by 3 weeks of odRH
Лекарство: 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
Другие имена:
  • two optimized-doses (odR) rifampicin
Лекарство: Isoniazid
50 mg tablet, dosed by weight and age
Другие имена:
  • Isoniazid (H)
Лекарство: Pyrazinamide
150 mg tablet, dosed by weight and age
Другие имена:
  • Pyrazinamide (Z)
Лекарство: Ethambutol
100 mg tablet, dosed by weight and age
Другие имена:
  • Ethambutol (E)
Лекарство: Rifampicin
standard of care and only the 75 mg tablet will be used
Другие имена:
  • standard dose rifampicin (R)
Экспериментальный: Arm 3: 14 week duration
N = 40, 8 weeks of odRHZE followed by 6 weeks of odRH
Лекарство: 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
Другие имена:
  • two optimized-doses (odR) rifampicin
Лекарство: Isoniazid
50 mg tablet, dosed by weight and age
Другие имена:
  • Isoniazid (H)
Лекарство: Pyrazinamide
150 mg tablet, dosed by weight and age
Другие имена:
  • Pyrazinamide (Z)
Лекарство: Ethambutol
100 mg tablet, dosed by weight and age
Другие имена:
  • Ethambutol (E)
Лекарство: Rifampicin
standard of care and only the 75 mg tablet will be used
Другие имена:
  • standard dose rifampicin (R)
Экспериментальный: Arm 4: 17 week duration
N = 40, 8 weeks of odRHZE followed by 9 weeks of odRH
Лекарство: 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
Другие имена:
  • two optimized-doses (odR) rifampicin
Лекарство: Isoniazid
50 mg tablet, dosed by weight and age
Другие имена:
  • Isoniazid (H)
Лекарство: Pyrazinamide
150 mg tablet, dosed by weight and age
Другие имена:
  • Pyrazinamide (Z)
Лекарство: Ethambutol
100 mg tablet, dosed by weight and age
Другие имена:
  • Ethambutol (E)
Лекарство: Rifampicin
standard of care and only the 75 mg tablet will be used
Другие имена:
  • standard dose rifampicin (R)
Активный компаратор: 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
Лекарство: 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
Другие имена:
  • two optimized-doses (odR) rifampicin
Лекарство: Isoniazid
50 mg tablet, dosed by weight and age
Другие имена:
  • Isoniazid (H)
Лекарство: Pyrazinamide
150 mg tablet, dosed by weight and age
Другие имена:
  • Pyrazinamide (Z)
Лекарство: Ethambutol
100 mg tablet, dosed by weight and age
Другие имена:
  • Ethambutol (E)
Лекарство: Rifampicin
standard of care and only the 75 mg tablet will be used
Другие имена:
  • standard dose rifampicin (R)
Экспериментальный: 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)
Лекарство: 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
Другие имена:
  • two optimized-doses (odR) rifampicin
Лекарство: Isoniazid
50 mg tablet, dosed by weight and age
Другие имена:
  • Isoniazid (H)
Лекарство: Pyrazinamide
150 mg tablet, dosed by weight and age
Другие имена:
  • Pyrazinamide (Z)
Лекарство: Ethambutol
100 mg tablet, dosed by weight and age
Другие имена:
  • Ethambutol (E)
Лекарство: Rifampicin
standard of care and only the 75 mg tablet will be used
Другие имена:
  • standard dose rifampicin (R)
Экспериментальный: 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)
Лекарство: 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
Другие имена:
  • two optimized-doses (odR) rifampicin
Лекарство: Isoniazid
50 mg tablet, dosed by weight and age
Другие имена:
  • Isoniazid (H)
Лекарство: Pyrazinamide
150 mg tablet, dosed by weight and age
Другие имена:
  • Pyrazinamide (Z)
Лекарство: Ethambutol
100 mg tablet, dosed by weight and age
Другие имена:
  • Ethambutol (E)
Лекарство: Rifampicin
standard of care and only the 75 mg tablet will be used
Другие имена:
  • standard dose rifampicin (R)

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Step 2: Unfavorable TB treatment outcome
Временное ограничение: 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

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
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
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

University of Wisconsin, Madison

Соавторы

National Institute of Allergy and Infectious Diseases (NIAID)

Следователи

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

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Оцененный)

1 сентября 2026 г.

Первичное завершение (Оцененный)

1 сентября 2030 г.

Завершение исследования (Оцененный)

1 сентября 2030 г.

Даты регистрации исследования

Первый отправленный

15 мая 2026 г.

Впервые представлено, что соответствует критериям контроля качества

15 июня 2026 г.

Первый опубликованный (Действительный)

18 июня 2026 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

18 июня 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

15 июня 2026 г.

Последняя проверка

1 июня 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • 2026-0205
  • SMPH | Pediatrics - GPAM (Другой идентификатор: UW Madison)
  • Protocol Version 2/10/26 (Другой идентификатор: UW Madison)
  • 1U01AI192041-01 (Грант/контракт NIH США)

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

ДА

Совместное использование IPD Поддерживающий тип информации

  • STUDY_PROTOCOL
  • САП
  • МКФ

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Нет

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

продукт, произведенный в США и экспортированный из США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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