Re-evaluating the Duration in Children of TB Treatment (REDUCE TB)
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.
調査の概要
詳細な説明
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
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：UW Clinical Trials Institute
- 電話番号：608.265.3132
- メール：info@clinicaltrials.wisc.edu
研究場所
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Lima、ペルー
- Socios en Salud Sucursal Peru
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主任研究者：
- Leonid Lecca, MD
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参加基準
適格基準
就学可能な年齢
- 子
健康ボランティアの受け入れ
説明
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)
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Arm 1: 8 week duration
N = 40, 8 weeks of odRHZE
|
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
他の名前：
50 mg tablet, dosed by weight and age
他の名前：
150 mg tablet, dosed by weight and age
他の名前：
100 mg tablet, dosed by weight and age
他の名前：
standard of care and only the 75 mg tablet will be used
他の名前：
|
|
実験的：Arm 2: 11 week duration
N = 40, 8 weeks of odRHZE followed by 3 weeks of odRH
|
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
他の名前：
50 mg tablet, dosed by weight and age
他の名前：
150 mg tablet, dosed by weight and age
他の名前：
100 mg tablet, dosed by weight and age
他の名前：
standard of care and only the 75 mg tablet will be used
他の名前：
|
|
実験的：Arm 3: 14 week duration
N = 40, 8 weeks of odRHZE followed by 6 weeks of odRH
|
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
他の名前：
50 mg tablet, dosed by weight and age
他の名前：
150 mg tablet, dosed by weight and age
他の名前：
100 mg tablet, dosed by weight and age
他の名前：
standard of care and only the 75 mg tablet will be used
他の名前：
|
|
実験的：Arm 4: 17 week duration
N = 40, 8 weeks of odRHZE followed by 9 weeks of odRH
|
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
他の名前：
50 mg tablet, dosed by weight and age
他の名前：
150 mg tablet, dosed by weight and age
他の名前：
100 mg tablet, dosed by weight and age
他の名前：
standard of care and only the 75 mg tablet will be used
他の名前：
|
|
アクティブコンパレータ：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
|
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
他の名前：
50 mg tablet, dosed by weight and age
他の名前：
150 mg tablet, dosed by weight and age
他の名前：
100 mg tablet, dosed by weight and age
他の名前：
standard of care and only the 75 mg tablet will be used
他の名前：
|
|
実験的：Step 1: PK - Dosing Schedule A > B
N = 15
Dosing schedules are by weight and age, with Schedule A a higher dose of RIF (totaling 250 - 1650mg) than Schedule B (totaling 200 - 1350mg) |
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
他の名前：
50 mg tablet, dosed by weight and age
他の名前：
150 mg tablet, dosed by weight and age
他の名前：
100 mg tablet, dosed by weight and age
他の名前：
standard of care and only the 75 mg tablet will be used
他の名前：
|
|
実験的：Step 1: PK - Dosing Schedule B > A
N = 15
Dosing schedules are by weight and age, with Schedule A a higher dose of RIF (totaling 250 - 1650mg) than Schedule B (totaling 200 - 1350mg) |
odR for main trial determined from Lead-in PK study 75 mg tablet, and 150 or 300 mg capsule, dosed by weight and age
他の名前：
50 mg tablet, dosed by weight and age
他の名前：
150 mg tablet, dosed by weight and age
他の名前：
100 mg tablet, dosed by weight and age
他の名前：
standard of care and only the 75 mg tablet will be used
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Step 2: Unfavorable TB treatment outcome
時間枠：48 weeks
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A participant has unfavorable treatment outcomes if they fail to meet either of the following criteria:
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48 weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
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
時間枠：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.
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data collected from individual participants for 2 regimens of 4 weeks each, up to 8 weeks total
|
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Step 1: Tolerability Measured by discontinuation of at least one drug in Lead-in PK study
時間枠：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
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Step 1: Pharmacokinetics of optimized-dose rifampicin: (AUC0-24)
時間枠：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)
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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)
時間枠：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
|
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Step 1: Acceptability of optimized-dose rifampicin summarized by participant count
時間枠：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.
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baseline (at dose 1), week 4, week 8
|
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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
時間枠：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
時間枠：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.
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up to 24 weeks
|
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Step 2: Lung function post-TB treatment
時間枠：week 48
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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):
|
week 48
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Step 2: Acceptability of optimized-dose rifampicin summarized by participant count
時間枠：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
|
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Step 2: Acceptability of overall TB treatment regimen summarized by participant count
時間枠：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
|
協力者と研究者
捜査官
- 主任研究者：Anthony Garcia-Prats, MD, MSc, PhD、UW School of Medicine and Public Health
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 2026-0205
- SMPH | Pediatrics - GPAM (その他の識別子：UW Madison)
- Protocol Version 2/10/26 (その他の識別子：UW Madison)
- 1U01AI192041-01 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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Rifampicinの臨床試験
-
Bin CaoMicuRx; Beijing Chest Hospital, Capital Medical University; Jiangxi Provincial Chest Hospital募集