A Phase 3 interventional study of rifapentine and rifapentine and moxifloxacin in Tuberculosis, sponsored by Centers for Disease Control and Prevention. Completed at 33 sites in 13 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2024-12-04.
Sponsored by Centers for Disease Control and Prevention · Phase 3, Interventional, and Treatment
The purpose of this study is to determine whether one or two four-month regimens of tuberculosis treatment are as effective as a standard six-month regimen for treatment of pulmonary tuberculosis (TB). All three regimens are administered daily, seven days each week, with direct observation of each dose by a health-care worker at least five of the seven days of each week.
The standard six-month regimen is two months of isoniazid, rifampin, ethambutol, and pyrazinamide followed by four months of isoniazid and rifampin.
The first short regimen is a single substitution of rifapentine for rifampin: two months of isoniazid, rifapentine, ethambutol, and pyrazinamide, followed by two months of isoniazid and rifapentine.
The second short regimen is a double substitution of rifapentine for rifampin and moxifloxacin for ethambutol: two months of isoniazid, rifapentine, moxifloxacin, and pyrazinamide, followed by two months of isoniazid, rifapentine, and moxifloxacin.
Target enrollment is 2500 participants. Each study participant will remain in the study for 18 months in order to include at least 12 months of evaluation of whether the participant's TB recurs.
Title:
Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis: a randomized, open-label, controlled, phase 3 clinical trial
Hypotheses:
A) Seventeen (17) week rifapentine-based regimen In previously untreated individuals with active drug-susceptible pulmonary tuberculosis treated with eight weeks of rifapentine (P), isoniazid (H), pyrazinamide (Z) and ethambutol (E) followed by nine weeks of rifapentine plus isoniazid, all given daily throughout, the proportion of participants who experience absence of cure (unfavorable outcome) will not be inferior to that observed in participants who are treated with a standard regimen (eight weeks of rifampin (R), isoniazid, pyrazinamide and ethambutol followed by eighteen weeks of rifampin plus isoniazid), all given daily throughout.
B) Seventeen (17) week rifapentine- plus moxifloxacin-containing regimen In previously untreated individuals with active drug-susceptible pulmonary tuberculosis treated with eight weeks of rifapentine, isoniazid, pyrazinamide and moxifloxacin (M), followed by nine weeks of rifapentine, isoniazid, and moxifloxacin, all given daily throughout, the proportion of participants who experience absence of cure (unfavorable outcome) will not be inferior to that observed in participants who are treated with a standard regimen (eight weeks of rifampin, isoniazid, pyrazinamide and ethambutol followed by eighteen weeks of rifampin plus isoniazid), all given daily throughout.
Phase: 3
Design: This will be an international, multicenter, randomized, controlled, open-label, 3-arm, phase 3 non-inferiority trial.
Population: Patients with newly diagnosed, previously untreated pulmonary tuberculosis.
Number of Sites: Multiple international sites, primarily sites of the Tuberculosis Trials Consortium and the AIDS Clinical Trials Group.
Study Duration: Duration per participant is approximately 18 months.
Description of Agent or Intervention: After written informed consent, participants will be randomly assigned to receive one of the following oral regimens:
Regimen 1 (control regimen): 2RHZE/4RH
Regimen 2 (investigational regimen): 2PHZE/2PH
Regimen 3 (investigational regimen): 2PHZM/2PHM
Objectives:
Primary:
Secondary:
Endpoints:
Primary Endpoints:
Secondary Endpoints:
1,170 studies on the registry are indexed under Tuberculosis; 175 are open to participants now.
This study's enrollment of 2,516 is above the median of 150 across 820 interventional studies indexed under Tuberculosis.
Browse Tuberculosis studies →Centers for Disease Control and Prevention is the lead sponsor of 275 studies on the registry; 2 are open to participants now.
Of its 11 completed or terminated interventional studies of FDA-regulated products, 8 (73%) 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.
Laboratory parameters done at or within 14 days prior to screening:
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.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
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.
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 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.
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.
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 drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
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.
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.
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.
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.
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.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
Eight weeks of daily treatment with rifampin, isoniazid, pyrazinamide, and ethambutol, followed by Eighteen weeks of daily treatment with rifampin and isoniazid All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered with each study dose. study drug doses: rifampin, 600 mg; isoniazid, 300 mg; pyrazinamide, \< 55kg 1000 mg, \>= 55-75 kg 1500 mg, \>75 kg 2000 mg; ethambutol, \< 55kg 800 mg, \>= 55-75 kg 1200 mg, \>75 kg 1600 mg
Drug: control
Eight weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and ethambutol, followed by Nine weeks of daily treatment with rifapentine and isoniazid All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered with each study dose. study drug doses: rifapentine 1200 mg; isoniazid, 300 mg; pyrazinamide, \< 55kg 1000 mg, \>= 55-75 kg 1500 mg, \>75 kg 2000 mg; ethambutol, \< 55kg 800 mg, \>= 55-75 kg 1200 mg, \>75 kg 1600 mg
Drug: rifapentine
Eight weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and moxifloxacin, followed by Nine weeks of daily treatment with rifapentine, isoniazid, and moxifloxacin All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered with each study dose. study drug doses: rifapentine 1200 mg; isoniazid, 300 mg; pyrazinamide, \< 55kg 1000 mg, \>= 55-75 kg 1500 mg, \>75 kg 2000 mg; moxifloxacin, 400 mg
Drug: rifapentine and moxifloxacin
Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment
Also known as: Priftin
Drug pages: Rifapentine · Moxifloxacin
Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol.
Also known as: Priftin and Avelox
standard six-month treatment
TB Disease-free Survival at 12M After Study Treatment Assignment Among Participants in Control Regimen, Regimen1 (2HRZE/4HR) to Experimental Regimens, Regimen3 (2HPZM/2HPM) and Regimen2 (2HPZ/2HP) (Modified Intent to Treat [MITT] Population)
To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis A primary outcome status of "favorable", "unfavorable", or "not assessable" was assigned. For detailed definitions of outcomes please refer to: Dorman SE, at al. N Engl J Med. 2021 May 6;384(18):1705-1718.
Time frame: Twelve months after treatment assignment
TB Disease-free Survival at 12M After Study Treatment Assignment Among Participants in Control Regimen, Regimen1 (2HRZE/4HR) to Experimental Regimens, Regimen3 (2HPZM/2HPM) and Regimen2 (2HPZ/2HP) (Assessable Population)
* To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis * To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis A primary outcome status of "favorable", "unfavorable", or "not assessable" was assigned. For detailed definitions of outcomes please refer to: Dorman SE, at al. N Engl J Med. 2021 May 6;384(18):1705-1718.
Time frame: Twelve months after treatment assignment
Percentage Participants With Grade 3 or Higher Adverse Events During Study Drug Treatment in Control Regimen (Regimen 1 2HRZE/4HR) Compared to Experimental Regimens, Regimen 3 (2HPZM/2HPM) and Regimen 2 (2HPZ/2HP) (Safety Analysis Population)
* To evaluate the Safety of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis * To evaluate the Safety of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis Grade 3 or higher Adverse Events are collected by Clinical sites in systematic way through the laboratory tests and physical exam during regular study follow up visits and also in a non-systematic way when it was self-reported by participants during the study visits. The events are graded by site investigators per Common Terminology Criteria for Adverse Events (CTCAE V4.03
Time frame: Four months and up to 14 days after last does of after study treatment (Regimen 2 and 3) or Six months and up to 14 days after last does of after study treatment (Regimen 1)
Proportion of Participants Who Are Culture Negative at Eight Weeks
Proportion of participants who are culture negative at eight weeks, liquid media
Time frame: eight weeks
Time to Stable Sputum Culture Conversion
Time to stable sputum culture conversion, liquid media
Time frame: four or six months
Discontinuation of Assigned Treatment for a Reason Other Than Microbiological Ineligibility (Tolerability)
Tolerability of the regimen is evaluated using the outcome of discontinuation of assigned treatment for a reason other than microbiological ineligibility.
Time frame: four or six months
Estimated Steady State Efavirenz PK Parameters Including Mid-dosing Interval Concentration
Among participants with HIV infection receiving efavirenz-based antiretroviral therapy, number of participants who maintained plasma efavirenz concentrations ≥1 mg/L during TB treatment.
Time frame: four months
TB Disease-free Survival at Eighteen Months After Study Treatment Assignment
* To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis * To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis
Time frame: Eighteen months after study treatment assignment.
TB Disease-free Survival at Eighteen Months After Study Treatment Assignment
* To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis * To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis
Time frame: Eighteen months after treatment assignment
Speed of Decline of Sputum Viable Bacilli by Automated Liquid MGIT Culture Days to Detection
Parameter estimates of the nonlinear mixed effect models describing longitudinal time to positive (TTP)
Time frame: 12 months
Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculosis Deaths Have an Unfavorable Outcome
A sensitivity analysis used to supplement the primary efficacy results and provide further insight into whether the intervention regimens should be considered to have non-inferior efficacy. This analysis considers the difference in proportion of unfavorable outcomes between the control arm and each of the experimental arms. Measurement Description: The difference in proportion unfavorable was calculated using a stratified analysis using Cochran-Mantel-Haenszel weights. The analysis was stratified by HIV status and presence of cavitation only, and the stratified difference was considered primary.
Time frame: 12 months
Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculosis Deaths Have a Favorable Outcome
A sensitivity analysis used to supplement the primary efficacy results and provide further insight into whether the intervention regimens should be considered to have non-inferior efficacy. This analysis considers the difference in proportion of unfavorable outcomes between the control arm and each of the experimental arms. Measurement Description: The difference in proportion unfavorable was calculated using a stratified analysis using Cochran-Mantel-Haenszel weights. The analysis was stratified by HIV status and presence of cavitation only, and the stratified difference was considered primary.
Time frame: 12 months
Participants were enrolled at 34 clinical research sites in 13 countries between January 2016 and October 2018. First participant was enrolled on 25 January 2016. Last participant was enrolled on 30 October 2018.
| Milestone | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Started | 829 | 838 | 849 |
| Microbiologically eligible analysis population | 768 | 784 | 791 |
| Assessable population | 726 | 752 | 756 |
| Completed | 726 | 752 | 756 |
| Not completed | 103 | 86 | 93 |
| Withdrew: Death | 3 | 4 | 8 |
| Withdrew: Lost to follow-up | 31 | 23 | 22 |
| Withdrew: Pregnancy | 8 | 4 | 5 |
| Withdrew: Protocol violation | 8 | 8 | 4 |
| Withdrew: Baseline drug resistance | 49 | 40 | 51 |
| Withdrew: No positive mycobacterium tuberculosis culture | 4 | 6 | 3 |
| Withdrew: Reinfection with a new strain of mtb | 0 | 1 | 0 |
To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis A primary outcome status of "favorable", "unfavorable", or "not assessable" was assigned. For detailed definitions of outcomes please refer to: Dorman SE, at al. N Engl J Med. 2021 May 6;384(18):1705-1718.
| Participants | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Favorable Outcome | 656 | 645 | 668 |
| Unfavorable Outcome | 112 | 139 | 123 |
* To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis * To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis A primary outcome status of "favorable", "unfavorable", or "not assessable" was assigned. For detailed definitions of outcomes please refer to: Dorman SE, at al. N Engl J Med. 2021 May 6;384(18):1705-1718.
| Participants | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Favorable | 656 | 645 | 668 |
| Unfavorable | 70 | 107 | 88 |
* To evaluate the Safety of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis * To evaluate the Safety of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis Grade 3 or higher Adverse Events are collected by Clinical sites in systematic way through the laboratory tests and physical exam during regular study follow up visits and also in a non-systematic way when it was self-reported by participants during the study visits. The events are graded by site investigators per Common Terminology Criteria for Adverse Events (CTCAE V4.03
| Participants | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Participants with Grade 3 or higher Adverse events | 159 | 119 | 159 |
| Participants with less than Grade 3 Adverse Events or no adverse events | 666 | 716 | 687 |
Proportion of participants who are culture negative at eight weeks, liquid media
| Participants | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Proportion of Participants Who Are Culture Negative at Eight Weeks | 523 | 616 | 641 |
Time to stable sputum culture conversion, liquid media
| weeks | Regimen 1 | Regimen 2 | Regimen 3 |
|---|---|---|---|
| Time to Stable Sputum Culture Conversion | 8.14 (8.00 to 12.14) | 8.14 (4.14 to 12.00) | 8.14 (4.14 to 8.29) |
Tolerability of the regimen is evaluated using the outcome of discontinuation of assigned treatment for a reason other than microbiological ineligibility.
| Participants | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Discontinuation of Assigned Treatment for a Reason Other Than Microbiological Ineligibility (Tolerability) | 61 | 37 | 55 |
Among participants with HIV infection receiving efavirenz-based antiretroviral therapy, number of participants who maintained plasma efavirenz concentrations ≥1 mg/L during TB treatment.
| Participants | EFV1 |
|---|---|
| Estimated Steady State Efavirenz PK Parameters Including Mid-dosing Interval Concentration | 62 |
* To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis * To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis
| Participants | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Favorable | 656 | 636 | 667 |
| Unfavorable | 112 | 148 | 124 |
* To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis * To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis
| Participants | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Favorable | 656 | 636 | 667 |
| Unfavorable | 69 | 97 | 79 |
Parameter estimates of the nonlinear mixed effect models describing longitudinal time to positive (TTP)
| log10 DTP / day | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Speed of Decline of Sputum Viable Bacilli by Automated Liquid MGIT Culture Days to Detection | 0.14 | 0.20 | 0.24 |
A sensitivity analysis used to supplement the primary efficacy results and provide further insight into whether the intervention regimens should be considered to have non-inferior efficacy. This analysis considers the difference in proportion of unfavorable outcomes between the control arm and each of the experimental arms. Measurement Description: The difference in proportion unfavorable was calculated using a stratified analysis using Cochran-Mantel-Haenszel weights. The analysis was stratified by HIV status and presence of cavitation only, and the stratified difference was considered primary.
| Participants | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPEZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculosis Deaths Have an Unfavorable Outcome | 656 | 645 | 668 |
A sensitivity analysis used to supplement the primary efficacy results and provide further insight into whether the intervention regimens should be considered to have non-inferior efficacy. This analysis considers the difference in proportion of unfavorable outcomes between the control arm and each of the experimental arms. Measurement Description: The difference in proportion unfavorable was calculated using a stratified analysis using Cochran-Mantel-Haenszel weights. The analysis was stratified by HIV status and presence of cavitation only, and the stratified difference was considered primary.
| Participants | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPEZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculosis Deaths Have a Favorable Outcome | 671 | 650 | 673 |
Collected over Adverse Events were reported from randomization to up to 14 days after last dose of study treatment Regimen (4 months and up to 14 days or 6 months and up to 14 days); All cause Mortality is reported during study treatment and up to M18 study follow up visit (18 months). Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Regimen 1 (2HRZE/4HR) | 12/825 (1.5%) | 56/825 (6.8%) | 74/825 (9%) |
| Regimen 2 (2HPZ/2HP) | 11/835 (1.3%) | 39/835 (4.7%) | 61/835 (7.3%) |
| Regimen 3 (2HPMZ/2HPM) | 13/846 (1.5%) | 37/846 (4.4%) | 94/846 (11.1%) |
| Event | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| HepatitisHepatobiliary disorders | 10/825 | 5/835 | 7/846 |
| HemoptysisRespiratory, thoracic and mediastinal disorders | 5/825 | 4/835 | 1/846 |
| NeutropeniaBlood and lymphatic system disorders | 3/825 | 1/835 | 2/846 |
| Deep Vein ThrombosisVascular disorders | 3/825 | 2/835 | 1/846 |
| PregnancyPregnancy, puerperium and perinatal conditions | 2/825 | 3/835 | 2/846 |
| PneumoniaInfections and infestations | 1/825 | 1/835 | 3/846 |
| UrticariaSkin and subcutaneous tissue disorders | 0/825 | 1/835 | 3/846 |
| Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders | 2/825 | 1/835 | 0/846 |
| Stab WoundInjury, poisoning and procedural complications | 1/825 | 2/835 | 0/846 |
| Diabetic RetinopathyEye disorders | 1/825 | 0/835 | 0/846 |
| Event | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) |
|---|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 48/825 | 34/835 | 56/846 |
| HepatitisHepatobiliary disorders | 26/825 | 27/835 | 38/846 |
Baseline Population Description: The population is the Microbiologically eligible population that included the randomized participants excluding the ones with no evidence of cultures positive for M. tuberculosis, or with resistance to one or more of isoniazid, rifampin or fluoroquinolones, or are enrolled in violation of eligibility criteria
| Age, Categorical(Participants) | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) | Total |
|---|---|---|---|---|
| <=18 years | 19 | 19 | 25 | 63 |
| Between 18 and 65 years | 743 | 755 | 755 | 2253 |
| >=65 years | 6 | 10 | 11 | 27 |
| Age, Continuous(years) | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) | Total |
|---|---|---|---|---|
| Median | 30.9 (24.9 to 41.0) | 31.0 (24.6 to 41.1) | 31.0 (24.6 to 41.5) | 31.0 (24.6 to 41.3) |
| Sex: Female, Male(Participants) | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) | Total |
|---|---|---|---|---|
| Female | 224 | 221 | 228 | 673 |
| Male | 544 | 563 | 563 | 1670 |
| Ethnicity (NIH/OMB)(Participants) | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 27 | 20 | 27 | 74 |
| Not Hispanic or Latino | 287 | 283 | 297 | 867 |
| Unknown or Not Reported | 454 | 481 | 467 | 1402 |
| Race (NIH/OMB)(Participants) | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 86 | 93 | 89 | 268 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 553 | 571 | 552 | 1676 |
| White | 15 | 8 | 13 | 36 |
| More than one race | 111 | 111 | 135 | 357 |
| Unknown or Not Reported | 3 | 1 | 2 | 6 |
| Region of Enrollment(Participants) | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) | Total |
|---|---|---|---|---|
| United States | 8 | 7 | 10 | 25 |
| Africa | 565 | 573 | 578 | 1716 |
| South Asia | 86 | 89 | 88 | 263 |
| South America | 109 | 115 | 115 | 339 |
| HIV Status(Participants) | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) | Total |
|---|---|---|---|---|
| HIV Negative | 704 | 716 | 729 | 2149 |
| HIV Positive | 64 | 68 | 62 | 194 |
| Cavitation status at Baseline(Participants) | Regimen 1 (2HRZE/4HR) | Regimen 2 (2HPZ/2HP) | Regimen 3 (2HPMZ/2HPM) | Total |
|---|---|---|---|---|
| Cavitation on chest radiograph | 558 | 573 | 572 | 1703 |
| No cavitation on chest radiograph | 204 | 205 | 210 | 619 |
| Unknown | 6 | 6 | 9 | 21 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Data being collected in CDISC format.
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Studies of the drugs tested here: Rifapentine · Moxifloxacin
Centers for Disease Control and Prevention →