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

15. Juni 2026 aktualisiert von: 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.

Studienübersicht

Status

Noch keine Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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

Studientyp

Interventionell

Einschreibung (Geschätzt)

230

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Kind

Akzeptiert gesunde Freiwillige

Nein

Beschreibung

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)

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Arm 1: 8 week duration
N = 40, 8 weeks of odRHZE
Arzneimittel: 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
Andere Namen:
  • two optimized-doses (odR) rifampicin
Arzneimittel: Isoniazid
50 mg tablet, dosed by weight and age
Andere Namen:
  • Isoniazid (H)
Arzneimittel: Pyrazinamide
150 mg tablet, dosed by weight and age
Andere Namen:
  • Pyrazinamide (Z)
Arzneimittel: Ethambutol
100 mg tablet, dosed by weight and age
Andere Namen:
  • Ethambutol (E)
Arzneimittel: Rifampicin
standard of care and only the 75 mg tablet will be used
Andere Namen:
  • standard dose rifampicin (R)
Experimental: Arm 2: 11 week duration
N = 40, 8 weeks of odRHZE followed by 3 weeks of odRH
Arzneimittel: 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
Andere Namen:
  • two optimized-doses (odR) rifampicin
Arzneimittel: Isoniazid
50 mg tablet, dosed by weight and age
Andere Namen:
  • Isoniazid (H)
Arzneimittel: Pyrazinamide
150 mg tablet, dosed by weight and age
Andere Namen:
  • Pyrazinamide (Z)
Arzneimittel: Ethambutol
100 mg tablet, dosed by weight and age
Andere Namen:
  • Ethambutol (E)
Arzneimittel: Rifampicin
standard of care and only the 75 mg tablet will be used
Andere Namen:
  • standard dose rifampicin (R)
Experimental: Arm 3: 14 week duration
N = 40, 8 weeks of odRHZE followed by 6 weeks of odRH
Arzneimittel: 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
Andere Namen:
  • two optimized-doses (odR) rifampicin
Arzneimittel: Isoniazid
50 mg tablet, dosed by weight and age
Andere Namen:
  • Isoniazid (H)
Arzneimittel: Pyrazinamide
150 mg tablet, dosed by weight and age
Andere Namen:
  • Pyrazinamide (Z)
Arzneimittel: Ethambutol
100 mg tablet, dosed by weight and age
Andere Namen:
  • Ethambutol (E)
Arzneimittel: Rifampicin
standard of care and only the 75 mg tablet will be used
Andere Namen:
  • standard dose rifampicin (R)
Experimental: Arm 4: 17 week duration
N = 40, 8 weeks of odRHZE followed by 9 weeks of odRH
Arzneimittel: 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
Andere Namen:
  • two optimized-doses (odR) rifampicin
Arzneimittel: Isoniazid
50 mg tablet, dosed by weight and age
Andere Namen:
  • Isoniazid (H)
Arzneimittel: Pyrazinamide
150 mg tablet, dosed by weight and age
Andere Namen:
  • Pyrazinamide (Z)
Arzneimittel: Ethambutol
100 mg tablet, dosed by weight and age
Andere Namen:
  • Ethambutol (E)
Arzneimittel: Rifampicin
standard of care and only the 75 mg tablet will be used
Andere Namen:
  • standard dose rifampicin (R)
Aktiver 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
Arzneimittel: 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
Andere Namen:
  • two optimized-doses (odR) rifampicin
Arzneimittel: Isoniazid
50 mg tablet, dosed by weight and age
Andere Namen:
  • Isoniazid (H)
Arzneimittel: Pyrazinamide
150 mg tablet, dosed by weight and age
Andere Namen:
  • Pyrazinamide (Z)
Arzneimittel: Ethambutol
100 mg tablet, dosed by weight and age
Andere Namen:
  • Ethambutol (E)
Arzneimittel: Rifampicin
standard of care and only the 75 mg tablet will be used
Andere Namen:
  • standard dose rifampicin (R)
Experimental: 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)
Arzneimittel: 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
Andere Namen:
  • two optimized-doses (odR) rifampicin
Arzneimittel: Isoniazid
50 mg tablet, dosed by weight and age
Andere Namen:
  • Isoniazid (H)
Arzneimittel: Pyrazinamide
150 mg tablet, dosed by weight and age
Andere Namen:
  • Pyrazinamide (Z)
Arzneimittel: Ethambutol
100 mg tablet, dosed by weight and age
Andere Namen:
  • Ethambutol (E)
Arzneimittel: Rifampicin
standard of care and only the 75 mg tablet will be used
Andere Namen:
  • standard dose rifampicin (R)
Experimental: 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)
Arzneimittel: 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
Andere Namen:
  • two optimized-doses (odR) rifampicin
Arzneimittel: Isoniazid
50 mg tablet, dosed by weight and age
Andere Namen:
  • Isoniazid (H)
Arzneimittel: Pyrazinamide
150 mg tablet, dosed by weight and age
Andere Namen:
  • Pyrazinamide (Z)
Arzneimittel: Ethambutol
100 mg tablet, dosed by weight and age
Andere Namen:
  • Ethambutol (E)
Arzneimittel: Rifampicin
standard of care and only the 75 mg tablet will be used
Andere Namen:
  • standard dose rifampicin (R)

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Step 2: Unfavorable TB treatment outcome
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

University of Wisconsin, Madison

Mitarbeiter

National Institute of Allergy and Infectious Diseases (NIAID)

Ermittler

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

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Geschätzt)

1. September 2026

Primärer Abschluss (Geschätzt)

1. September 2030

Studienabschluss (Geschätzt)

1. September 2030

Studienanmeldedaten

Zuerst eingereicht

15. Mai 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

15. Juni 2026

Zuerst gepostet (Tatsächlich)

18. Juni 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

18. Juni 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

15. Juni 2026

Zuletzt verifiziert

1. Juni 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • 2026-0205
  • SMPH | Pediatrics - GPAM (Andere Kennung: UW Madison)
  • Protocol Version 2/10/26 (Andere Kennung: UW Madison)
  • 1U01AI192041-01 (US NIH Stipendium/Vertrag)

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

JA

Art der unterstützenden IPD-Freigabeinformationen

  • STUDIENPROTOKOLL
  • SAFT
  • ICF

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Produkt, das in den USA hergestellt und aus den USA exportiert wird

Nein

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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