A Phase 3 interventional study of Isoniazid and Rifampin in Tuberculosis, Tuberculosis, Pulmonary and Tuberculosis, Lymph Node, sponsored by Johns Hopkins University. Recruiting at 9 sites in 7 countries. Open to participants aged 0 Days to 9 Years. Per ClinicalTrials.gov, last updated 2026-07-24.
Sponsored by Johns Hopkins University · Phase 3, Interventional, and Treatment
While drug-susceptible tuberculosis (TB) disease in children currently requires four to six months of treatment, most children may be able to be cured with a shorter treatment of more powerful drugs. Shorter treatment may be easier for children to tolerate and finish as well as ease caregiver strain from managing treatment side effects and supporting children over many months. The primary objective of this study is to evaluate if a 2-month regimen (including isoniazid (H), rifapentine (P), pyrazinamide (Z) and moxifloxacin (M)) is as safe and effective as a 4- to 6-month regimen (isoniazid, rifampicin (R), pyrazinamide, ethambutol (E)) in curing drug-susceptible TB disease in children under 10 years old. The study is also evaluating the safety of the HPZM in children with and without HIV.
In previously untreated individuals with presumed drug-susceptible pulmonary and or peripheral lymph node TB treated with eight weeks of rifapentine, isoniazid, pyrazinamide and moxifloxacin (2HPZM), all given daily throughout, the proportion of participants who experience absence of cure (unsuccessful outcome) will not be inferior to that observed in participants who are treated with the standard regimen (eight weeks of rifampin, isoniazid, pyrazinamide, with or without ethambutol followed by 8 to 16 weeks of rifampin plus isoniazid depending on disease severity) all given daily throughout.
319 studies on the registry are indexed under Tuberculosis, Pulmonary; 71 are open to participants now.
This study's planned enrollment of 860 is above the median of 146 across 227 interventional studies indexed under Tuberculosis, Pulmonary.
Browse Tuberculosis, Pulmonary studies →Johns Hopkins University is the lead sponsor of 1,815 studies on the registry; 315 are open to participants now.
Of its 208 completed or terminated interventional studies of FDA-regulated products, 144 (69%) have results posted.
Compared within Tuberculosis, Pulmonary, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Tuberculosis. The counts are of registry records indexed under each term, refreshed daily. How we classify →
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.
At Entry, diagnosed with TB disease, defined as:
Has normal, Grade 1 or 2 test results for all of the following done at or within 14 days of Entry (including the most recent):
For children living with HIV:
For participants who are engaging in sexual activity that could lead to pregnancy (self-reported): agrees to practice at least one non-hormonal method of or abstain from heterosexual intercourse during study drug treatment and for 30 days after stopping study medications. Non-hormonal methods include:
Exclusion Criteria:
Any known to taking any study drug:
Late Exclusions:
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.
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.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
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.
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 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.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
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.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
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.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
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.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
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.
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.
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.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
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.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
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.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
8 weeks of daily HRZ(E) followed by either 16 or 24 weeks of daily HR, per local standard of care
Drug: Isoniazid · Drug: Rifampin · Drug: Pyrazinamide · Drug: Ethambutol
8 weeks of daily HPZM
Drug: Isoniazid · Drug: Pyrazinamide · Drug: Rifapentine · Drug: Moxifloxacin
Once daily weight-based dose
Also known as: H
Once daily weight-based dose
Also known as: R
Once daily weight-based dose
Also known as: Z
Once daily weight-based dose
Also known as: E
Once daily weight-based dose
Also known as: P, Priftin
Once daily weight-based dose
Also known as: M, Avelox
TB disease-free survival at 48-weeks
Non-inferiority will be assessed by comparing the upper bound of a 95%, 2-sided confidence interval for the difference between the proportion of participants who are classified as having an unsuccessful outcome on the control regimen (HRZ(E)) and the intervention regimen (HPZM) to the predefined non-inferiority margin of 6% at 48 weeks.
Time frame: Measured from study entry through week 48
Proportion of participants with grade 3 or higher adverse events over 28 weeks
The proportion of participants with a Grade 3 or higher adverse event and the corresponding 95% confidence intervals will be generated. An exact test for equality of proportions will be used to compare safety outcomes between the arms.
Time frame: Measured from study entry through Week 28
TB disease-free survival at 48-weeks
Non-inferiority will be assessed by comparing the upper bound of a 95%, 2-sided confidence interval for the difference between the proportion of participants who are classified as having an unsuccessful outcome on the control regimen (HRZ(E)) and the intervention regimen (HPZM) to the predefined non-inferiority margin of 6% at 48 weeks.
Time frame: Measured from study entry through Week 48
TB disease-free survival at 72-weeks
Non-inferiority will be assessed by comparing the upper bound of a 95%, 2-sided confidence interval for the difference between the proportion of participants who are classified as having an unsuccessful outcome on the control regimen (HRZ(E)) and the intervention regimen (HPZM) to the predefined non-inferiority margin of 6% at 72 weeks.
Time frame: Measured from study entry through Week 72
Adherence to treatment regimens
The per-protocol analysis will account for variations in adherence to the treatment regimens. Inverse probability of treatment weighting (IPTW) using propensity scores will be applied and the net difference in treatment failure rates between the two treatment regimens and the 95% confidence interval around this will be calculated to determine non-inferiority.
Time frame: Measured from study entry through Week 48
Tolerability as assessed by proportion of participants who discontinue treatment
Tolerability will be assessed as discontinuation of the assigned treatment for a reason other than microbiological ineligibility (AEs assessed as related to the study regimen that led to permanent discontinuation of the regimen, participant refusal, parent/guardian prematurely discontinues, etc.) among the modified intention-to-treat population. Proportion of participants who discontinue the assigned study regimen and the corresponding 95% confidence intervals will be generated. The control regimen (HRZ(E)) will be compared against the intervention regimen (HPZM) using an exact test for equality of proportions.
Time frame: Week 8 (intervention/HPZM) or Week 16 or Week 24 (control/HRZ(E))
Rifapentine Area under the curve (AUC0-24)
Area under the curve from start of dose to 24 hours post-dose. Measured at Week 4 or Week 8. Blood samples drawn at 0, 1 minute, 2 minutes, 4 hours and 6 hours post dose.
Time frame: Measured from study entry through Week 8
Rifapentine minimal concentration (Cmin)
Minimal concentration from start of dose to 24 hours post-dose. Measured at Week 4 or Week 8. Blood samples drawn at 0, 1 minute, 2 minutes, 4 hours and 6 hours post dose.
Time frame: Measured from study entry through Week 8
Rifapentine peak concentration (Cmax)
Peak concentration from start of dose to 24 hours post-dose. Measured at Week 4 or Week 8. Blood samples drawn at 0, 1 minute, 2 minutes, 4 hours and 6 hours post dose.
Time frame: Measured from study entry through Week 8
Moxifloxacin AUC0-24
Area under the curve from start of dose to 24 hours post-dose. Measured at Week 4 or Week 8. Blood samples drawn at 0, 1 minute, 2 minutes, 4 hours and 6 hours post dose.
Time frame: Measured from study entry through Week 8
Moxifloxacin Cmin
Minimal concentration from start of dose to 24 hours post-dose. Measured at Week 4 or Week 8. Blood samples drawn at 0, 1 minute, 2 minutes, 4 hours and 6 hours post dose.
Time frame: Measured from study entry through Week 8
Moxifloxacin Cmax
Peak concentration from start of dose to 24 hours post-dose. Measured at Week 4 or Week 8. Blood samples drawn at 0, 1 minute, 2 minutes, 4 hours and 6 hours post dose.
Time frame: Measured from study entry through Week 8
Parent/guardian and/or participant reported palatability and acceptability of study regimen
Based on questionnaire developed by study team, data will be aggregated to measure acceptability at Entry, Week 4, and Week 8 (all participants), and Weeks 16 and 24 (for those who continue on HRZ(E) only). Scoring based on a likert or likert-like scale for each question. Each question is scored 1 to 5 with higher scores reflecting increased acceptability.
Time frame: Baseline, Week 4, Week 8 (Regimens 1 and 2) and at Weeks 16 and 24 (Regimen 1 only)
Adherence as assessed by proportion of participants who have taken at least 90% of their doses
Adherence measures will be documented by a treatment supporter on a TB treatment card (as per local practice), by pill count and by an adherence questionnaire and descriptively summarized for all participants. Participants are considered adherent who have taken at least 90% of their doses within the 8 week, 16 week or 24-week time frame of their regimen.
Time frame: Baseline through Week 8 for HPZM, Week 16 for HRZ(E) with non-severe disease, or Week 24 for HRZ(E) with severe disease
Risk Stratification Algorithm
If the study outcome is not non-inferior, pragmatic, programmatically available data will be considered for inclusion in a risk stratification algorithm that would aim to identify children at high risk of unsuccessful TB treatment outcome who may benefit from a longer duration of therapy. The efficacy endpoint will be analyzed using mixed-effects logistic regression models to identify predictors. The models will be adjusted for World Bank country income categories and by site using random intercepts. Univariable and multivariable analysis will be performed. The association between baseline clinical predictors and unsuccessful treatment outcomes will be analyzed, Treatment characteristics will then be added to the models to determine if treatment helped in the description of the primary efficacy endpoint.
Time frame: Measured from study entry through Week 48
Cost effectiveness as assessed by the incremental cost-effective ratio (ICER)
ICER: Total costs of HPZM minus the total costs 16 or 24 week HRZE, divided by the total number of disability-adjusted life-year (DALY) averted for HPZM minus the total DALYs averted for 16- or 24-week HRZE.
Time frame: Measured from study entry through Week 24
Dolutegravir AUC0-24
Area under the curve from start of dose to 24 hours post-dose. Measured at Week 4 or 8 and at between Weeks 12-28. Blood samples drawn at 0, 1 hour, 4 hours and 6 hours post dose.
Time frame: Measured from study entry through Week 28
Dolutegravir Cmin
Minimal concentration from start of dose to 24 hours post-dose. Measured at Week 4 or 8 and at between Weeks 12-28. Blood samples drawn at 0, 1 hour, 4 hours and 6 hours post dose.
Time frame: Measured from study entry through Week 28
Dolutegravir Cmax
Peak concentration from start of dose to 24 hours post-dose. Measured at Week 4 or 8 and at between Weeks 12-28. Blood samples drawn at 0, 1 hour, 4 hours and 6 hours post dose.
Time frame: Measured from study entry through Week 28
Proportion of children living with HIV
Among participants living with HIV, the proportions of participants in each study arm who achieve or maintain virologic control (\< 200 copies/mL) at Weeks 24 and 48 will be presented in aggregate, as well as broken down by weight bands (if the sample sizes are sufficient) bounded by 95% confidence intervals.
Time frame: Week 24 and Week 48
Plan to share: Yes — Make individual participant data, after de-identification, publicly available in accordance with USAID's policy on data sharing.
Time frame: After study completion, de-identified data that can be legally released to the public may be released.
Access criteria: With whom: Researchers who provide a methodologically sound proposal for the use of the data per USAID's policy on data sharing and in accordance with in-country data sharing agreements. For what types of analysis: To achieve aims specified in the researcher's approved proposal. By what mechanisms will data be available: To be determined.
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Studies of the drugs tested here: Rifapentine · Moxifloxacin