A Phase 2 interventional study of Isoniazid and Rifampin in Tuberculosis, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Not yet recruiting at 29 sites in 16 countries. Open to participants aged 13 Years and older. Per ClinicalTrials.gov, last updated 2026-08-19.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2, Interventional, and Treatment
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.
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:
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.
1,170 studies on the registry are indexed under Tuberculosis; 175 are open to participants now.
This study's planned enrollment of 900 is above the median of 150 across 820 interventional studies indexed under Tuberculosis.
Browse Tuberculosis studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Has laboratory test results within 7 days before study entry that meet all of the following:
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 method during study treatment and for 30 days after stopping study drugs. Acceptable methods include:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Isoniazid · Drug: Rifampin · Drug: Pyrazinamide · Drug: Ethambutol
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.
Drug: Isoniazid · Drug: Pyrazinamide · Drug: Rifapentine · Drug: Moxifloxacin
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.
Drug: Isoniazid · Drug: Rifampin · Drug: Pyrazinamide · Drug: Ethambutol
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.
Drug: Isoniazid · Drug: Pyrazinamide · Drug: Rifapentine · Drug: Moxifloxacin
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.
Drug: Isoniazid · Drug: Pyrazinamide · Drug: Rifapentine · Drug: Moxifloxacin
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.
Drug: Isoniazid · Drug: Pyrazinamide · Drug: Rifapentine · Drug: Moxifloxacin
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.
Drug: Isoniazid · Drug: Pyrazinamide · Drug: Rifapentine · Drug: Moxifloxacin
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.
Drug: Isoniazid · Drug: Pyrazinamide · Drug: Rifapentine · Drug: Moxifloxacin
Administered orally once daily
Administered orally once daily
Administered orally once daily
Administered orally once daily
Administered orally once daily
Administered orally once daily
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.
Time frame: 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.
Time frame: Baseline through 28 weeks after randomization
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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: Baseline through 26 weeks after randomization
Plan to share: Yes — Individual participant data that underlie results in the publication, after deidentification.
Supporting information: Study protocol, Statistical analysis plan
Time frame: 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.
Access criteria: 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.
No publications or documents are linked to this record.
Start is estimated for Oct 2026; primary completion for Jun 2029, 31 months later.
Of 43 non-industry phase 2 interventional studies under Tuberculosis, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 15 and three quarters within 37. This study's planned 31 months is above that.
Counting every sponsor, half of 63 studies reached it within 24 months; a quarter within 15 and three quarters within 36.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Rifapentine · Moxifloxacin
National Institute of Allergy and Infectious Diseases (NIAID) →