Questa pagina è stata tradotta automaticamente e l'accuratezza della traduzione non è garantita. Si prega di fare riferimento al Versione inglese per un testo di partenza.

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

15 giugno 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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

Tipo di studio

Interventistico

Iscrizione (Stimato)

230

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Perù
      • Lima, Perù
        • Socios en Salud Sucursal Peru
        • Investigatore principale:
          • Leonid Lecca, MD

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Bambino

Accetta volontari sani

No

Descrizione

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)

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Arm 1: 8 week duration
N = 40, 8 weeks of odRHZE
Droga: 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
Altri nomi:
  • two optimized-doses (odR) rifampicin
Droga: Isoniazid
50 mg tablet, dosed by weight and age
Altri nomi:
  • Isoniazid (H)
Droga: Pyrazinamide
150 mg tablet, dosed by weight and age
Altri nomi:
  • Pyrazinamide (Z)
Droga: Ethambutol
100 mg tablet, dosed by weight and age
Altri nomi:
  • Ethambutol (E)
Droga: Rifampicin
standard of care and only the 75 mg tablet will be used
Altri nomi:
  • standard dose rifampicin (R)
Sperimentale: Arm 2: 11 week duration
N = 40, 8 weeks of odRHZE followed by 3 weeks of odRH
Droga: 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
Altri nomi:
  • two optimized-doses (odR) rifampicin
Droga: Isoniazid
50 mg tablet, dosed by weight and age
Altri nomi:
  • Isoniazid (H)
Droga: Pyrazinamide
150 mg tablet, dosed by weight and age
Altri nomi:
  • Pyrazinamide (Z)
Droga: Ethambutol
100 mg tablet, dosed by weight and age
Altri nomi:
  • Ethambutol (E)
Droga: Rifampicin
standard of care and only the 75 mg tablet will be used
Altri nomi:
  • standard dose rifampicin (R)
Sperimentale: Arm 3: 14 week duration
N = 40, 8 weeks of odRHZE followed by 6 weeks of odRH
Droga: 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
Altri nomi:
  • two optimized-doses (odR) rifampicin
Droga: Isoniazid
50 mg tablet, dosed by weight and age
Altri nomi:
  • Isoniazid (H)
Droga: Pyrazinamide
150 mg tablet, dosed by weight and age
Altri nomi:
  • Pyrazinamide (Z)
Droga: Ethambutol
100 mg tablet, dosed by weight and age
Altri nomi:
  • Ethambutol (E)
Droga: Rifampicin
standard of care and only the 75 mg tablet will be used
Altri nomi:
  • standard dose rifampicin (R)
Sperimentale: Arm 4: 17 week duration
N = 40, 8 weeks of odRHZE followed by 9 weeks of odRH
Droga: 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
Altri nomi:
  • two optimized-doses (odR) rifampicin
Droga: Isoniazid
50 mg tablet, dosed by weight and age
Altri nomi:
  • Isoniazid (H)
Droga: Pyrazinamide
150 mg tablet, dosed by weight and age
Altri nomi:
  • Pyrazinamide (Z)
Droga: Ethambutol
100 mg tablet, dosed by weight and age
Altri nomi:
  • Ethambutol (E)
Droga: Rifampicin
standard of care and only the 75 mg tablet will be used
Altri nomi:
  • standard dose rifampicin (R)
Comparatore attivo: 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
Droga: 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
Altri nomi:
  • two optimized-doses (odR) rifampicin
Droga: Isoniazid
50 mg tablet, dosed by weight and age
Altri nomi:
  • Isoniazid (H)
Droga: Pyrazinamide
150 mg tablet, dosed by weight and age
Altri nomi:
  • Pyrazinamide (Z)
Droga: Ethambutol
100 mg tablet, dosed by weight and age
Altri nomi:
  • Ethambutol (E)
Droga: Rifampicin
standard of care and only the 75 mg tablet will be used
Altri nomi:
  • standard dose rifampicin (R)
Sperimentale: 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)
Droga: 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
Altri nomi:
  • two optimized-doses (odR) rifampicin
Droga: Isoniazid
50 mg tablet, dosed by weight and age
Altri nomi:
  • Isoniazid (H)
Droga: Pyrazinamide
150 mg tablet, dosed by weight and age
Altri nomi:
  • Pyrazinamide (Z)
Droga: Ethambutol
100 mg tablet, dosed by weight and age
Altri nomi:
  • Ethambutol (E)
Droga: Rifampicin
standard of care and only the 75 mg tablet will be used
Altri nomi:
  • standard dose rifampicin (R)
Sperimentale: 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)
Droga: 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
Altri nomi:
  • two optimized-doses (odR) rifampicin
Droga: Isoniazid
50 mg tablet, dosed by weight and age
Altri nomi:
  • Isoniazid (H)
Droga: Pyrazinamide
150 mg tablet, dosed by weight and age
Altri nomi:
  • Pyrazinamide (Z)
Droga: Ethambutol
100 mg tablet, dosed by weight and age
Altri nomi:
  • Ethambutol (E)
Droga: Rifampicin
standard of care and only the 75 mg tablet will be used
Altri nomi:
  • standard dose rifampicin (R)

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Step 2: Unfavorable TB treatment outcome
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

University of Wisconsin, Madison

Collaboratori

National Institute of Allergy and Infectious Diseases (NIAID)

Investigatori

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

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 settembre 2026

Completamento primario (Stimato)

1 settembre 2030

Completamento dello studio (Stimato)

1 settembre 2030

Date di iscrizione allo studio

Primo inviato

15 maggio 2026

Primo inviato che soddisfa i criteri di controllo qualità

15 giugno 2026

Primo Inserito (Effettivo)

18 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

18 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

15 giugno 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 2026-0205
  • SMPH | Pediatrics - GPAM (Altro identificatore: UW Madison)
  • Protocol Version 2/10/26 (Altro identificatore: UW Madison)
  • 1U01AI192041-01 (Sovvenzione/contratto NIH degli Stati Uniti)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Tipo di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO
  • LINFA
  • ICF

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su Tubercolosi

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in Denmark

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

Sottoscrivi