TuberculosisPhase 2NCT07595042
A Trial of Stratified Patient-Centered Treatment Regimens for Active TB (SPECTRA-TB)
A Phase 2 study testing Isoniazid, Rifampin and Pyrazinamide in people with Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 29 sites in 16 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Isoniazid, Rifampin and Pyrazinamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 900 participants
- Where
- 29 sitesin 16 countries
- Study dates
- 30 Oct 2026to 22 Oct 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
29 sites in 16 countries. Contact the study team or a site near you to ask about taking part.
29 sites in 16 countries
Peru4 sites
Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC) (Site # 31970)
Callao
Fanny Rosas, RN, frosas@citbm.pe
Barranco CRS (Site #: 11301)
Lima
Consuelo Ramirez, C.N.M., 51-1-2067800 ext. 210, ctristan@impactaperu.org
San Miguel CRS (Site # 11302)
Lima
Helen Chapa, RN, hchapa@impactaperu.org
Socios en Salud Sucursal Peru CRS (Site # 31985)
Lima
Bruno Martel, R.N., M.Sc., bmartel_ses@pih.org
Thailand4 sites
Siriraj Hospital, Mahidol University NICHD CRS (Site # 5115)
Bangkok
Watcharee Lermankul, Ph.D, watcharee.ler@sipid.org
Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS (Site #: 31784)
Chiang Mai, 50200
Daralak Tavornprasit, R.N., M.Sc., 66-5-3936148 ext. 176, daralak.t@cmu.ac.th
Chiangrai Prachanukroh Hospital NICHD CRS (Site # 5116)
Chiang Rai
Timothy Cressey, Ph. D, tim.cressey@cmu.ac.th
Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (Site #: 31802)
Pathum Wan, Bangkok, 10330
Parawee Thongpaeng, 662-6523040 ext. 106, parawee.t@hivnat.org
Botswana2 sites
Gaborone CRS (Site #: 12701)
Gaborone
Unoda Chakalisa, MBBCh, 267-3930388, uchakalisa@bhp.org.bw
Molepolole CRS (Site # 12702)
Gaborone
Mpho Raesi, BN, mraesi@bhp.org.bw
Brazil2 sites
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS (Site #: 12101)
Rio de Janeiro, 21040-360
Brenda Hoagland, M.D., 55-21-38659122, brenda.hoagland@ini.fiocruz.br
Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS (Site # 12201)
Rio Grande
Rita Cassia, MD, Lrita@ghc.com.br
Haiti2 sites
GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS (Site #: 31730)
Port-au-Prince, HT-6110
Yvetot Joseph, MD, 509-36832867, yvetotjoseph@gheskio.org
Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS (Site #: 30022)
Port-au-Prince, HT-6110
Jean Bernard Marc, 509-29426327, marcjeanbernard1@gheskio.org
India2 sites
YRG CARE CRS (Site # 32075)
Chennai
Rifa Khan, M.B.B.S., M.P.H., rifa@yrgcare.org
Byramjee Jeejeebhoy Government Medical College (BJGMC) CRS (Site #: 31441)
Pune, Maharashtra, 411001
Nishi Suryavanshi, Ph.D., 91-98-23248979, nsuryav1@jhmi.edu
Kenya2 sites
Moi University Clinical Research Center (MUCRC) CRS (Site #: 12601)
Eldoret, Rift Valley, 30100
Viola C. Kirui, 254-711729856, viola.kirui@gmail.com
Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS (Site #: 12501)
Kericho, Rift Valley, 20200
Samwel K. Chirchir, R.N., B.Sc., 254-52-2036100, Samwel.Chirchir@usamru-k.org
Malawi2 sites
Blantyre CRS (Site #: 30301)
Blantyre
Dumisile Huwa, 265-1811885, dhuwa@jhp.mw
Malawi CRS (Site #: 12001)
Lilongwe, Central Region
Thokozani Makuhunga, 1-265-1755056, tmakuhunga@unclilongwe.org
Uganda2 sites
Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site (Site #: 12401)
Kampala, 10005
Sandra Rwambuya, M.P.H., 256-772-779283, dxr23@case.edu
MU-JHU Research Collaboration (MUJHU CARE LTD) CRS (Site # 30293)
Kampala
Deo Wabwire, M.B.Ch.B., M.Med., dwabwire@mujhu.org
Argentina1 site
Fundacion Huesped CRS (Site # 31957)
Buenos Aires
Daniela Converso, daniela.converso@huesped.org.ar
Australia1 site
Vietnam-University of Sydney CRS (Site # 32495)
Sydney
Yen Pham, yen.phamngoc@sydneyvietnaminstitute.org
Mexico1 site
Nutrición-Mexico CRS (Site #: 32078)
Mexico City, 14000
Brenda Crabtree Ramirez, 52-5554870900 ext. 5504, brenda.crabtree@infecto.mx
Philippines1 site
TB HIV Innovations and Clinical Research Foundation Corp. (Site #: 31981)
Dasmariñas, Cavite, 4114
Maria Gler, MD, 63-9178230431, msgler@tbhivicr.org.ph
Tanzania1 site
Kilimanjaro Christian Medical Centre (KCMC) (Site # 5118)
Moshi
Boniface Njau, M. Sc., bnneneu@gmail.com
Vietnam1 site
National Lung Hospital (Site #: 32483)
Hanoi, 100000
Tran Viet Ha, 84-912-785886, vietha@live.unc.edu
Zimbabwe1 site
Milton Park CRS (Site #: 30313)
Harare, 263663
Patience N. Sibanda, 263-774-361790, psibanda@uz-ctrc.org
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Tuberculosis
- Being tested
- Isoniazid, Rifampin, Pyrazinamide, Ethambutol, Rifapentine
- Keywords
- Tuberculosis, Pulmonary tuberculosis, Drug-susceptible tuberculosis, Rifampin-susceptible tuberculosis, Rifapentine, Moxifloxacin, HIV coinfection, Treatment shortening, Risk-stratified treatment
- Medical subject headings
- Tuberculosis, Tuberculosis, Pulmonary, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsoniazidDrug
Administered orally once daily
RifampinDrug
Administered orally once daily
PyrazinamideDrug
Administered orally once daily
EthambutolDrug
Administered orally once daily
RifapentineDrug
Administered orally once daily
MoxifloxacinDrug
Administered orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Arm 1A: Higher-risk control group | Active comparator | 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. Receives: Drug: Isoniazid; Drug: Rifampin; Drug: Pyrazinamide; Drug: Ethambutol |
| Arm 1B: Higher-risk experimental group | Experimental | 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. Receives: Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin |
| Arm 2A: Lower-risk control group | Active comparator | 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. Receives: Drug: Isoniazid; Drug: Rifampin; Drug: Pyrazinamide; Drug: Ethambutol |
| Arm 2B: Lower-risk experimental group (10 week duration) | Experimental | 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. Receives: Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin |
| Arm 2C: Lower-risk experimental group (12 week duration) | Experimental | 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. Receives: Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin |
| Arm 2D: Lower-risk experimental group (14 week duration) | Experimental | 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. Receives: Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin |
| Arm 2E: Lower-risk experimental group (16 week duration) | Experimental | 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. Receives: Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin |
| Arm 2F: Lower-risk experimental group (18 week duration) | Experimental | 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. Receives: Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lower-risk group: Proportion of participants with sustained cure at 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.
Measured: 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
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.
Measured: Baseline through 28 weeks after randomization
Secondary outcomes (6)
Higher-risk group: Proportion of participants with sustained cure at 52 week 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.
Measured: 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
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.
Measured: Baseline through 28 weeks after randomization
Proportion of participants with sustained cure at 72 weeks after randomization
Sustained cure defined as for the primary efficacy outcome measure, except assessed with respect to 72 weeks.
Measured: 72 weeks after randomization
Cumulative proportion of stable liquid mycobacterial culture conversion by 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).
Measured: Baseline through 26 weeks after randomization
Mean liquid mycobacterial culture log10 days to positivity slope during the first 10 weeks after randomization
Liquid mycobacterial culture days to positivity during the 10 weeks following randomization.
Measured: During the first 10 weeks after randomization
Proportion of participants who prematurely discontinue study treatment
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.
Measured: Baseline through 26 weeks after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2026
- Study start30 Oct 2026 (estimated)
- Primary completion5 Jun 2029 (estimated)
- Study completion22 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 900 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- ViiV Healthcare
- Responsible party
- Sponsor
- Investigators
- Gustavo Velásquez, MD, MPH, Study chair, University of California, San FranciscoPatrick Phillips, PhD, Study chair, San Francisco General HospitalSusan Dorman, MD, Study chair, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07595042
- Sponsor's protocol ID
- A5414
- Other IDs
- 38987
- Status last verified
- Aug 2026
- First submitted
- 6 May 2026
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.