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A Trial of Stratified Patient-Centered Treatment Regimens for Active TB (SPECTRA-TB)

17 août 2026 mis à jour par: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase 2C Trial of Stratified Patient-Centered Treatment Regimens for Active TB

The A5414 study will evaluate whether treatment for drug-susceptible pulmonary tuberculosis (TB) can be tailored according to a participant's risk of an unfavorable outcome. Participants will be assigned to lower-risk or higher-risk groups using baseline characteristics and then randomized within each group to receive either standard TB treatment or an investigational rifapentine- and moxifloxacin-containing regimen. The study will evaluate whether shorter treatment durations may be used in lower-risk participants and whether the investigational regimen may improve outcomes in higher-risk participants. Safety and tolerability will also be evaluated.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Description détaillée

SPECTRA-TB is a Phase 2C, randomized, open-label trial of stratified medicine principles in TB treatment to identify the optimal duration of the HP1500ZM regimen for participants in the lower-risk stratum and to demonstrate improved TB-related favorable outcomes of this regimen in the higher-risk stratum. The study risk stratification includes a higher-risk group (1 control arm and 1 experimental arm) and a lower-risk group (1 control and 5 experimental arms).

Eligible participants will be stratified as either lower- or higher-risk based on the risk stratification algorithm which is based on the following results obtained during the screening period: Xpert MTB/RIF Ultra CT value, extent of disease on chest X-ray, age, BMI, sex at birth, diabetes status, and HIV status using the SPECTRA-TB risk algorithm prior to randomization. Those classified into the lower-risk group (consisting of the low and moderate risk randomization strata to facilitate balancing of risk within each lower-risk treatment arm) will be randomized to SOC or one of five durations of the experimental regimens while those classified into the higher-risk group will be randomized to receive either SOC or a single fixed duration of the experimental regimen. The lower and higher-risk groups will have the following arms:

  • Lower-risk: 10, 12, 14, 16, 18, and 26 weeks (5 experimental arms [weeks 10-18] and one 26-week SOC arm with 100 participants in each arm).
  • Higher-risk: Two arms with 26 weeks duration (one SOC arm with 100 participants and one experimental arm with 200 participants).

All participants will be followed for 72 weeks from randomization for outcomes of efficacy, safety, and tolerability. Participants will be monitored closely for Possible Poor Treatment Response (PPTR), TB treatment failure or TB recurrence, safety, tolerability, and loss to follow-up.

Type d'étude

Interventionnel

Inscription (Estimé)

900

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • Argentine
  • Australie
  • Bostwana
      • Gaborone, Bostwana
        • Gaborone CRS (Site #: 12701)
        • Contact:
      • Gaborone, Bostwana
  • Brésil
      • Rio Grande, Brésil
        • Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS (Site # 12201)
        • Contact:
      • Rio de Janeiro, Brésil, 21040-360
        • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS (Site #: 12101)
        • Contact:
  • Haïti
      • Port-au-Prince, Haïti, HT-6110
        • GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS (Site #: 31730)
        • Contact:
      • Port-au-Prince, Haïti, HT-6110
        • Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS (Site #: 30022)
        • Contact:
  • Inde
      • Chennai, Inde
        • YRG CARE CRS (Site # 32075)
        • Contact:
    • Maharashtra
      • Pune, Maharashtra, Inde, 411001
        • Byramjee Jeejeebhoy Government Medical College (BJGMC) CRS (Site #: 31441)
        • Contact:
          • Nishi Suryavanshi, Ph.D.
          • Numéro de téléphone: 91-98-23248979
          • E-mail: nsuryav1@jhmi.edu
  • Kenya
    • Rift Valley
      • Eldoret, Rift Valley, Kenya, 30100
        • Moi University Clinical Research Center (MUCRC) CRS (Site #: 12601)
        • Contact:
      • Kericho, Rift Valley, Kenya, 20200
        • Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS (Site #: 12501)
        • Contact:
  • Malawi
      • Blantyre, Malawi
        • Blantyre CRS (Site #: 30301)
        • Contact:
          • Dumisile Huwa
          • Numéro de téléphone: 265-1811885
          • E-mail: dhuwa@jhp.mw
    • Central Region
      • Lilongwe, Central Region, Malawi
        • Malawi CRS (Site #: 12001)
        • Contact:
  • Mexique
      • Mexico City, Mexique, 14000
        • Nutrición-Mexico CRS (Site #: 32078)
        • Contact:
  • Ouganda
      • Kampala, Ouganda, 10005
        • Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site (Site #: 12401)
        • Contact:
          • Sandra Rwambuya, M.P.H.
          • Numéro de téléphone: 256-772-779283
          • E-mail: dxr23@case.edu
      • Kampala, Ouganda
        • MU-JHU Research Collaboration (MUJHU CARE LTD) CRS (Site # 30293)
        • Contact:
  • Philippines
    • Cavite
      • Dasmariñas, Cavite, Philippines, 4114
        • TB HIV Innovations and Clinical Research Foundation Corp. (Site #: 31981)
        • Contact:
  • Pérou
      • Callao, Pérou
        • Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC) (Site # 31970)
        • Contact:
      • Lima, Pérou
        • Barranco CRS (Site #: 11301)
        • Contact:
      • Lima, Pérou
      • Lima, Pérou
        • Socios en Salud Sucursal Peru CRS (Site # 31985)
        • Contact:
  • Tanzanie
      • Moshi, Tanzanie
        • Kilimanjaro Christian Medical Centre (KCMC) (Site # 5118)
        • Contact:
  • Thaïlande
      • Bangkok, Thaïlande
        • Siriraj Hospital, Mahidol University NICHD CRS (Site # 5115)
        • Contact:
      • Chiang Mai, Thaïlande, 50200
        • Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS (Site #: 31784)
        • Contact:
          • Daralak Tavornprasit, R.N., M.Sc.
          • Numéro de téléphone: 176 66-5-3936148
          • E-mail: daralak.t@cmu.ac.th
      • Chiang Rai, Thaïlande
        • Chiangrai Prachanukroh Hospital NICHD CRS (Site # 5116)
        • Contact:
    • Bangkok
      • Pathum Wan, Bangkok, Thaïlande, 10330
        • Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (Site #: 31802)
        • Contact:
  • Viêt Nam
      • Hanoi, Viêt Nam, 100000
        • National Lung Hospital (Site #: 32483)
        • Contact:
  • Zimbabwe
      • Harare, Zimbabwe, 263663
        • Milton Park CRS (Site #: 30313)
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Enfant
  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

Inclusion Criteria:

  • Has pulmonary tuberculosis (TB) that is likely to respond to standard TB medicines (drug-susceptible TB), based on sputum testing done within 7 days before entering the study. The test must show Mycobacterium tuberculosis is present, with no rifamycin resistance detected and no known resistance to isoniazid or fluoroquinolones.
  • Has a SPECTRA-TB risk score and risk group assigned during screening using the study-specific calculator.
  • Has a Karnofsky performance score of 50 or higher within 30 days before entering the study.
  • Has documented HIV-1 status (either with HIV or without HIV) based on acceptable testing.
  • If living with HIV, has a CD4+ cell count of at least 50 cells/mm3 within 60 days before study entry.
  • If living with HIV, is currently receiving or plans to start an efavirenz-based or dolutegravir-based antiretroviral therapy regimen by study week 8.

  • Has laboratory test results within 7 days before study entry that meet all of the following:

    • alanine aminotransferase (ALT) no more than 3 times the upper limit of normal
    • total bilirubin no more than 2.5 times the upper limit of normal
    • creatinine no more than 2 times the upper limit of normal
    • potassium between 3.5 and 5.5 mEq/L
    • absolute neutrophil count at least 1000/mm3
    • hemoglobin at least 7.0 g/dL
    • platelet count at least 100,000/mm3
  • If able to become pregnant, has a negative blood or urine pregnancy test within 7 days before study entry.

  • If able to become pregnant and sexually active in a way that could lead to pregnancy, agrees not to try to become pregnant and agrees to use at least 1 reliable non-hormonal birth control method during study treatment and for 30 days after stopping study drugs. Acceptable methods include:

    • condoms
    • intrauterine device (IUD) or intrauterine system (IUS)
    • cervical cap with spermicide
    • diaphragm with spermicide
  • If not able to become pregnant, has a history or documentation of menopause, hysterectomy, bilateral removal of the ovaries, or bilateral tubal ligation.
  • Has a verifiable address or place of residence and is willing to tell the study team about any change of address during treatment and follow-up.
  • Is willing and able to give informed consent, or assent with permission from a parent or legal guardian if required.

Exclusion Criteria:

  • TB bacteria are known to be resistant to 1 or more of the following medicines: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.
  • Received more than 5 days of treatment for active TB within the 24 weeks before study entry.
  • Received more than 5 days of treatment within the 30 days before study entry with certain TB medicines or related antibiotics, including isoniazid, rifampin, rifapentine, ethambutol, moxifloxacin, pyrazinamide, aminoglycosides, fluoroquinolones, linezolid, bedaquiline, pretomanid, and other specified anti-TB drugs.
  • Has suspected or confirmed TB involving the brain or central nervous system, bones, joints, heart lining (pericardium), or miliary TB.
  • Has a past history of suspected or confirmed drug-resistant TB of any type.
  • Is currently pregnant or breastfeeding.
  • Cannot take medicines by mouth.
  • Has an HIV/AIDS-related opportunistic infection at study entry.
  • Has acute or chronic hepatitis B, unless the hepatitis B infection has cleared.
  • Has acute or chronic hepatitis C, unless the hepatitis C infection has cleared or has been successfully treated.
  • Has alcohol-related liver disease.
  • Has liver cirrhosis.
  • Has a history of aortic aneurysm or aortic dissection.
  • Has a known history of long QT syndrome, a first-degree relative with long QT syndrome, or a screening ECG showing QTcF greater than 470 ms that does not correct with treatment of contributing factors.
  • Is taking other medicines that can prolong the QT interval and cannot safely switch to an alternative medicine.
  • Has a known history of acute intermittent porphyria.
  • Weighs less than 30 kg.
  • Is currently using, or is expected to need within 24 weeks after enrollment, 1 or more medicines that are not allowed during the study.
  • Has a known allergy, sensitivity, or hypersensitivity to any of the study drugs or their ingredients.
  • Has active drug or alcohol use, dependence, mental illness, or another serious infection that, in the opinion of the site investigator, could make it hard to follow the study requirements.
  • Is currently taking part in another interventional clinical trial.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: Arm 1A: Higher-risk control group
Participants at higher risk of unfavorable outcome will receive 26 weeks of standard-of-care treatment consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by isoniazid and rifampin for 18 weeks.
Médicament: Isoniazid
Administered orally once daily
Médicament: Rifampin
Administered orally once daily
Médicament: Pyrazinamide
Administered orally once daily
Médicament: Ethambutol
Administered orally once daily
Expérimental: Arm 1B: Higher-risk experimental group
Participants at higher risk of unfavorable outcome will receive 26 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.
Médicament: Isoniazid
Administered orally once daily
Médicament: Pyrazinamide
Administered orally once daily
Médicament: Rifapentine
Administered orally once daily
Médicament: Moxifloxacin
Administered orally once daily
Comparateur actif: Arm 2A: Lower-risk control group
Participants at lower risk of unfavorable outcome will receive 26 weeks of standard-of-care treatment consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by isoniazid and rifampin for 18 weeks.
Médicament: Isoniazid
Administered orally once daily
Médicament: Rifampin
Administered orally once daily
Médicament: Pyrazinamide
Administered orally once daily
Médicament: Ethambutol
Administered orally once daily
Expérimental: Arm 2B: Lower-risk experimental group (10 week duration)
Participants at lower risk of unfavorable outcome will receive 10 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.
Médicament: Isoniazid
Administered orally once daily
Médicament: Pyrazinamide
Administered orally once daily
Médicament: Rifapentine
Administered orally once daily
Médicament: Moxifloxacin
Administered orally once daily
Expérimental: Arm 2C: Lower-risk experimental group (12 week duration)
Participants at lower risk of unfavorable outcome will receive 12 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.
Médicament: Isoniazid
Administered orally once daily
Médicament: Pyrazinamide
Administered orally once daily
Médicament: Rifapentine
Administered orally once daily
Médicament: Moxifloxacin
Administered orally once daily
Expérimental: Arm 2D: Lower-risk experimental group (14 week duration)
Participants at lower risk of unfavorable outcome will receive 14 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.
Médicament: Isoniazid
Administered orally once daily
Médicament: Pyrazinamide
Administered orally once daily
Médicament: Rifapentine
Administered orally once daily
Médicament: Moxifloxacin
Administered orally once daily
Expérimental: Arm 2E: Lower-risk experimental group (16 week duration)
Participants at lower risk of unfavorable outcome will receive 16 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.
Médicament: Isoniazid
Administered orally once daily
Médicament: Pyrazinamide
Administered orally once daily
Médicament: Rifapentine
Administered orally once daily
Médicament: Moxifloxacin
Administered orally once daily
Expérimental: Arm 2F: Lower-risk experimental group (18 week duration)
Participants at lower risk of unfavorable outcome will receive 18 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.
Médicament: Isoniazid
Administered orally once daily
Médicament: Pyrazinamide
Administered orally once daily
Médicament: Rifapentine
Administered orally once daily
Médicament: Moxifloxacin
Administered orally once daily

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Lower-risk group: Proportion of participants with sustained cure at 52 weeks after randomization
Délai: 52 weeks after randomization
Sustained cure is defined as: participant known to be alive at or after 52 weeks after randomization; sustained culture negativity at 52 weeks after randomization, defined as the last 2 liquid cultures collected at different visits being Mtb-negative without an intervening Mtb-positive result, with the last collected no earlier than 48 weeks after randomization; no treatment failure or relapse through 52 weeks after randomization; and no retreatment or additional TB treatment beyond assigned study treatment through 52 weeks after randomization. Participants will be classified as having presence of sustained cure, absence of sustained cure, or not assessable.
52 weeks after randomization
Lower-risk group: Proportion of participants with at least 1 new Grade 3 to 5 adverse event through 28 weeks after randomization
Délai: Baseline through 28 weeks after randomization
Occurrence of at least 1 new Grade 3 to 5 adverse event during the 28 weeks following randomization among participants in the lower-risk group, where 28 weeks is 2 weeks beyond the longest scheduled treatment duration of 26 weeks.
Baseline through 28 weeks after randomization

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Higher-risk group: Proportion of participants with sustained cure at 52 week after randomization
Délai: 52 weeks after randomization
Sustained cure is defined as: participant known to be alive at or after 52 weeks after randomization; sustained culture negativity at 52 weeks after randomization, defined as the last 2 liquid cultures collected at different visits being Mtb-negative without an intervening Mtb-positive result, with the last collected no earlier than 48 weeks after randomization; no treatment failure or relapse through 52 weeks after randomization; and no retreatment or additional TB treatment beyond assigned study treatment through 52 weeks after randomization. Participants will be classified as having presence of sustained cure, absence of sustained cure, or not assessable.
52 weeks after randomization
Higher-risk group: Proportion of participants with at least 1 new Grade 3 to 5 adverse event through 28 weeks after randomization
Délai: Baseline through 28 weeks after randomization
Occurrence of at least 1 new Grade 3 to 5 adverse event during the 28 weeks following randomization among participants in the higher-risk group, where 28 weeks is 2 weeks beyond the longest scheduled treatment duration of 26 weeks.
Baseline through 28 weeks after randomization
Proportion of participants with sustained cure at 72 weeks after randomization
Délai: 72 weeks after randomization
Sustained cure defined as for the primary efficacy outcome measure, except assessed with respect to 72 weeks.
72 weeks after randomization
Cumulative proportion of stable liquid mycobacterial culture conversion by 26 weeks after randomization
Délai: Baseline through 26 weeks after randomization
Stable culture conversion is defined as two negative cultures on two different days without an intervening positive culture (irrespective of positive cultures subsequent to stable culture conversion).
Baseline through 26 weeks after randomization
Mean liquid mycobacterial culture log10 days to positivity slope during the first 10 weeks after randomization
Délai: During the first 10 weeks after randomization
Liquid mycobacterial culture days to positivity during the 10 weeks following randomization.
During the first 10 weeks after randomization
Proportion of participants who prematurely discontinue study treatment
Délai: Baseline through 26 weeks after randomization
Occurrence of premature study treatment discontinuation for any reason other than when the participant has tuberculosis subsequently determined to be resistant to isoniazid, rifampicin, or fluoroquinolones.
Baseline through 26 weeks after randomization

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborateurs

ViiV Healthcare

Les enquêteurs

  • Chaise d'étude: Susan Dorman, MD, Medical University of South Carolina
  • Chaise d'étude: Gustavo Velásquez, MD, MPH, University of California, San Francisco
  • Chaise d'étude: Patrick Phillips, PhD, San Francisco General Hospital

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

30 octobre 2026

Achèvement primaire (Estimé)

5 juin 2029

Achèvement de l'étude (Estimé)

22 octobre 2029

Dates d'inscription aux études

Première soumission

6 mai 2026

Première soumission répondant aux critères de contrôle qualité

12 mai 2026

Première publication (Réel)

19 mai 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

19 août 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

17 août 2026

Dernière vérification

1 août 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • A5414
  • 38987 (Autre identifiant: DAIDS-ES ID)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

Individual participant data that underlie results in the publication, after deidentification.

Délai de partage IPD

Beginning 3 months following publication and available throughout period of funding of the ACTG (Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections) by NIH.

Critères d'accès au partage IPD

  • With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG.
  • For what types of analyses? To achieve aims in the proposal approved by the ACTG.
  • By what mechanism will data be made available? Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data.

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE
  • SÈVE

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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