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| Name | Class |
|---|---|
| Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections | NETWORK |
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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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Regimen 1 | Active Comparator | 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 |
|
| Regimen 2 | Experimental | 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 |
|
| Regimen 3 | Experimental | 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 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rifapentine | Drug | Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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) |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants Who Are Culture Negative at Eight Weeks | Proportion of participants who are culture negative at eight weeks, liquid media | eight weeks |
| Time to Stable Sputum Culture Conversion |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Inclusion Criteria:
Suspected pulmonary tuberculosis plus one or both of the following: a) at least one sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF testing, with semiquantitative result of 'medium' or 'high' and rifamycin resistance not detected.
Age twelve (12) years or older
A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period.
Women of child-bearing potential who are not surgically sterilized must agree to practice a barrier method of contraception or abstain from heterosexual intercourse during study drug treatment.
Documentation of HIV infection status.
For HIV-positive individuals, CD4 T cell count greater than or equal to 100 cells/mm3 based on testing performed at or within 30 days prior to screening.
Laboratory parameters done at or within 14 days prior to screening:
For women of childbearing potential, a negative pregnancy test at or within seven (7) days prior to screening
Karnofsky score greater than or equal to 60
Written informed consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Susan Dorman, MD | Medical University of South Carolina | Study Chair |
| Payam Nahid, MD, MPH | University of California at San Francisco | Study Chair |
| Susan Swindells, MBBS | University of Nebraska | Study Chair |
| Richard Chaisson, MD | Johns Hopkins University | Study Chair |
| Ekaterina V Kurbatova, MD, PhD, MPH | Centers for Disease Control and Prevention | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| TBTC Site 82/ ACTG Site 801 USCF AIDS CRS | San Francisco | California | 94110 | United States | ||
| TBTC Site 24 Columbia Unversity |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39477924 | Derived | Chang VK, Imperial MZ, Phillips PPJ, Velasquez GE, Nahid P, Vernon A, Kurbatova EV, Swindells S, Chaisson RE, Dorman SE, Johnson JL, Weiner M, Jindani A, Harrison T, Sizemore EE, Whitworth W, Carr W, Bryant KE, Burton D, Dooley KE, Engle M, Nsubuga P, Diacon AH, Nhung NV, Dawson R, Savic RM; AIDS Clinical Trial Group; Tuberculosis Trials Consortium. Risk-stratified treatment for drug-susceptible pulmonary tuberculosis. Nat Commun. 2024 Oct 30;15(1):9400. doi: 10.1038/s41467-024-53273-7. | |
| 39012226 |
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Data being collected in CDISC format.
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Of 5214 participants screened, 2049 did not meet the eligible criteria, 405 declined to participate and site decided not to enroll 145 participants. 2516 participants were randomized Participants were required to have at least one sputum specimen positive for acid-fast bacilli by smear microscopy or positive for M. tuberculosis by Xpert MTB/RIF testing with semiquantitative result of medium or highand susceptible to isoniazid, rifampin, and fluoroquinolones
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Regimen 1 (2HRZE/4HR) | 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 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 control: standard six-month treatment |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 22, 2020 |
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| rifapentine and moxifloxacin | Drug | Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
|
|
| control | Drug | standard six-month treatment |
|
|
| 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) |
Time to stable sputum culture conversion, liquid media
| 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. | 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. | four months |
| TB Disease-free Survival at Eighteen Months After Study Treatment Assignment |
| Eighteen months after study treatment assignment. |
| TB Disease-free Survival at Eighteen Months After Study Treatment Assignment |
| 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) | 12 months |
| 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. | 12 months |
| New York |
| New York |
| 10032 |
| United States |
| TBTC Site 20 UNTHSC (University of North Texas Health Science Center) | Fort Worth | Texas | 76104 | United States |
| TBTC Site 62 Baylor College of Medicine & Affiliated Hospitals/VA | Houston | Texas | 77030 | United States |
| TBTC Site 63 San Antonio VA Medical Center (South Texas Group) | San Antonio | Texas | 78229-4404 | United States |
| TBTC Site 94/ ACTG Site 12201 Hospital Nossa Senhora da Conceicao | Porto Alegre | Rio Grande do Sul | 91350-200 | Brazil |
| TBTC Site 91/ ACTG Site 12101 Insituto Nacional de Pesquisa Clínica Evandro Chagas | Rio de Janeiro | 21040-360 | Brazil |
| TBTC Site 36 TB and Chest Service of Hong Kong, China | Hong Kong | China |
| TBTC Site 67/ ACTG Site 31730 GHESKIO centers IMIS | Port-au-Prince | Ouest | HT 6124 | Haiti |
| TBTC Site 45/ ACTG Site 30022: Les Centres Gheskio (INLR) | Port-au-Prince | Ouest | HT6110 | Haiti |
| TBTC Site 43/ ACTG Site 31441 BJ Medical College | Pune | Maharashtra | 4110011 | India |
| TBTC Site 44/ ACTG Site 11701 CART CRS, YRGCARE Medical Centre VHS | Chennai | Tamil Nadu | 600113 | India |
| TBTC Site 02/ ACTG 12501 Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS | Kericho | Kericho County | 20200 | Kenya |
| TBTC Site 39/ ACTG Site 31460 Kisumu CRS | Kisumu | Nyanza Province | 40100 | Kenya |
| TBTC Site 03/ ACTG Site 12601 Moi University Clinical Research Site | Eldoret | 30100 | Kenya |
| TBTC Site 04/ ACTG Site 30301 Blantyre CRS (or College of Medicine - Johns Hopkins Research Project, COM-JHP) | Blantyre | Malawi |
| TBTC Site 05/ ACTG Site 12001 UNC Project Tidziwe Centre | Lilongwe | Malawi |
| TBTC Site 90/ ACTG Site 11301 Asociacion Civil Impacta Salud y Educacion | Lima | Lima 04 | Peru |
| TBTC Site 93/ ACTG Site 11302 CRS San Miguel | Lima | Lima 32 | Peru |
| TBTC Site 10/ ACTG Site 31718 TASK Applied Science | Bellville | Cape Town | 7530 | South Africa |
| TBTC Site 09/ ACTG Site 31792 University of Cape Town Lung Institute (Pty) Ltd | Mowbray | Cape Town | 7700 | South Africa |
| TBTC Site 34 Wits Health Consortium Perinatal HIV Research Unit (PHRU) | Soweto | Gauteng | 1864 | South Africa |
| TBTC Site 49/ ACTG Site 12301 Soweto ACTG CRS | Soweto | Johannesburg | 2013 | South Africa |
| TBTC Site 06/ ACTG Site 11201 Durban International Clinical Research Site | Durban | KwaZulu-Natal | 4093 | South Africa |
| TBTC Site 01/ACTG Site 8950 FAM CRU | Parow Valley | Western Cape | 7505 | South Africa |
| TBTC Site 08/ ACTG Site 31793 South African Tuberculosis Vaccine Initiative (SATVI) | Cape Town | Western Province | 7705 | South Africa |
| TBTC Site 07/ ACTG Site 11101 Wits Helen Joseph CRS | Johannesburg | 2092 | South Africa |
| TBTC Site 42/ ACTG Site 31802 The Thai Red Cross AIDS Research Centre | Pathumwan | Bangkok | 10330 | Thailand |
| TBTC Site 69/ ACTG Site 31784 Thai-CTIU, CMU HIV Treatment CRS | Muang Chiang Mai | Chiang Mai | 50200 | Thailand |
| TBTC Site 11/ ACTG Site 12401 Joint Clinical Research Centre, Kampala Clinical Research Site | Kampala | Uganda |
| TBTC Site 30 Uganda-Case Western Reserve Research Collaboration | Kampala | Uganda |
| TBTC Site 37 Vietnam NTP/UCSF Research Collaboration | Hanoi | 10000 | Vietnam |
| TBTC Site 41/ ACTG Site 30313 Parirenyatwa Clinical Research Site | Harare | 263 | Zimbabwe |
| Derived |
| Xu AY, Velasquez GE, Zhang N, Chang VK, Phillips PPJ, Nahid P, Dorman SE, Kurbatova EV, Whitworth WC, Sizemore E, Bryant K, Carr W, Brown NE, Engle ML, Nhung NV, Nsubuga P, Diacon A, Dooley KE, Chaisson RE, Swindells S, Savic RM. Pyrazinamide Safety, Efficacy, and Dosing for Treating Drug-Susceptible Pulmonary Tuberculosis: A Phase 3, Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2024 Dec 1;210(11):1358-1369. doi: 10.1164/rccm.202401-0165OC. |
| 38462673 | Derived | Ngo HX, Xu AY, Velasquez GE, Zhang N, Chang VK, Kurbatova EV, Whitworth WC, Sizemore E, Bryant K, Carr W, Weiner M, Dooley KE, Engle M, Dorman SE, Nahid P, Swindells S, Chaisson RE, Nsubuga P, Lourens M, Dawson R, Savic RM. Pharmacokinetic-Pharmacodynamic Evidence From a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis. Clin Infect Dis. 2024 Jun 14;78(6):1680-1689. doi: 10.1093/cid/ciae119. |
| 36790881 | Derived | Kurbatova EV, Phillips PPJ, Dorman SE, Sizemore EE, Bryant KE, Purfield AE, Ricaldi J, Brown NE, Johnson JL, Wallis CL, Akol JP, Ocheretina O, Van Hung N, Mayanja-Kizza H, Lourens M, Dawson R, Nhung NV, Pierre S, Musodza Y, Shenje J, Badal-Faesen S, Vilbrun SC, Waja Z, Peddareddy L, Scott NA, Yuan Y, Goldberg SV, Swindells S, Chaisson RE, Nahid P. A Standardized Approach for Collection of Objective Data to Support Outcome Determination for Late-Phase Tuberculosis Clinical Trials. Am J Respir Crit Care Med. 2023 May 15;207(10):1376-1382. doi: 10.1164/rccm.202206-1118OC. |
| 36041016 | Derived | Pettit AC, Phillips PPJ, Kurbatova E, Vernon A, Nahid P, Dawson R, Dooley KE, Sanne I, Waja Z, Mohapi L, Podany AT, Samaneka W, Savic RM, Johnson JL, Muzanyi G, Lalloo UG, Bryant K, Sizemore E, Scott N, Dorman SE, Chaisson RE, Swindells S; Tuberculosis Trials Consortium (TBTC) Study 31/AIDS Clinical Trials Group (ACTG) A5349 study team. Rifapentine With and Without Moxifloxacin for Pulmonary Tuberculosis in People With Human Immunodeficiency Virus (S31/A5349). Clin Infect Dis. 2023 Feb 8;76(3):e580-e589. doi: 10.1093/cid/ciac707. |
| 34918028 | Derived | Podany AT, Pham M, Sizemore E, Martinson N, Samaneka W, Mohapi L, Badal-Faesen S, Dawson R, Johnson JL, Mayanja H, Lalloo U, Whitworth WC, Pettit A, Campbell K, Phillips PPJ, Bryant K, Scott N, Vernon A, Kurbatova EV, Chaisson RE, Dorman SE, Nahid P, Swindells S, Dooley KE, Fletcher CV. Efavirenz Pharmacokinetics and Human Immunodeficiency Virus Type 1 (HIV-1) Viral Suppression Among Patients Receiving Tuberculosis Treatment Containing Daily High-Dose Rifapentine. Clin Infect Dis. 2022 Sep 10;75(4):560-566. doi: 10.1093/cid/ciab1037. |
| 33951360 | Derived | Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. N Engl J Med. 2021 May 6;384(18):1705-1718. doi: 10.1056/NEJMoa2033400. |
| 33794353 | Derived | Scott NA, Lee KK, Sadowski C, Kurbatova EV, Goldberg SV, Nsubuga P, Kitshoff R, Whitelaw C, Thuy HN, Batra K, Allen-Blige C, Davis H, Kim J, Phan M, Fedrick P, Chiu KW, Heilig CM, Sizemore E; AIDS Clinical Trials Group and The Tuberculosis Trials Consortium. Optimizing drug inventory management with a web-based information system: The TBTC Study 31/ACTG A5349 experience. Contemp Clin Trials. 2021 Jun;105:106377. doi: 10.1016/j.cct.2021.106377. Epub 2021 Mar 29. |
| 33713841 | Derived | Bryant KE, Yuan Y, Engle M, Kurbatova EV, Allen-Blige C, Batra K, Brown NE, Chiu KW, Davis H, Elskamp M, Fagley M, Fedrick P, Hedges KNC, Narunsky K, Nassali J, Phan M, Phan H, Purfield AE, Ricaldi JN, Robergeau-Hunt K, Whitworth WC, Sizemore EE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Central monitoring in a randomized, open-label, controlled phase 3 clinical trial for a treatment-shortening regimen for pulmonary tuberculosis. Contemp Clin Trials. 2021 May;104:106355. doi: 10.1016/j.cct.2021.106355. Epub 2021 Mar 10. |
| 31981713 | Derived | Dorman SE, Nahid P, Kurbatova EV, Goldberg SV, Bozeman L, Burman WJ, Chang KC, Chen M, Cotton M, Dooley KE, Engle M, Feng PJ, Fletcher CV, Ha P, Heilig CM, Johnson JL, Lessem E, Metchock B, Miro JM, Nhung NV, Pettit AC, Phillips PPJ, Podany AT, Purfield AE, Robergeau K, Samaneka W, Scott NA, Sizemore E, Vernon A, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group and the Tuberculosis Trials Consortium. High-dose rifapentine with or without moxifloxacin for shortening treatment of pulmonary tuberculosis: Study protocol for TBTC study 31/ACTG A5349 phase 3 clinical trial. Contemp Clin Trials. 2020 Mar;90:105938. doi: 10.1016/j.cct.2020.105938. Epub 2020 Jan 22. |
| FG001 | Regimen 2 (2HPZ/2HP) | 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 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 rifapentine: Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment |
| FG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
| Microbiologically Eligible Analysis Population | Microbiologically Eligible Population included all enrolled participants that received a treatment assignment but excluded the participants 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 |
|
| Assessable Population | Excluded the Microbiologically eligible participants without an assessable outcome (if they were not already classified as unfavorable and additionally did not attend12M visit but were culture negative when last seen, or had treatment changed due to pregnancy, or died during follow-up with cause unrelated to tuberculosis, or received additional treatment for tuberculosis following exogenous reinfection shown by whole genome sequencing, or died from a violent or accidental death during treatment |
|
| COMPLETED | Completed Population included all participants that are randomized and are microbiologically eligible with an Assessable outcome (Assessable Population) |
|
| NOT COMPLETED |
|
|
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
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Regimen 1 (2HRZE/4HR) | 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 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 control: standard six-month treatment |
| BG001 | Regimen 2 (2HPZ/2HP) | 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 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 rifapentine: Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment |
| BG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| HIV Status | Randomization was stratified by the presence of cavitation on chest radiograph at baseline (since cavitation is associated with a decreased rate of microbiological response to TB treatment) and by HIV status (HIV-uninfected vs. HIV-infected). | Count of Participants | Participants |
| |||||||||||||||
| Cavitation status at Baseline | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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 | Posted | Count of Participants | Participants | Twelve months after treatment assignment |
|
|
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | 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) |
| Excluded Microbiologically eligible participants without an assessable outcomes, if they were not already classified as unfavorable and also did not attend 12M visit but were culture negative when last seen, or had treatment changed due to pregnancy, or died during follow-up with cause unrelated to tuberculosis, or received additional treatment for tuberculosis following exogenous reinfection demonstrated by whole genome sequencing, or died from a violent or accidental death during treatment | Posted | Count of Participants | Participants | Twelve months after treatment assignment |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | 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) |
| Safety analyses included all randomized participants who received at least one dose of study treatment | Posted | Count of Participants | Participants | 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) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Participants Who Are Culture Negative at Eight Weeks | Proportion of participants who are culture negative at eight weeks, liquid media | Microbiologically eligible analysis population, evaluable patients (positive or negative culture result) | Posted | Count of Participants | Participants | eight weeks |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Stable Sputum Culture Conversion | Time to stable sputum culture conversion, liquid media | Microbiologically Eligible Analysis Population | Posted | Median | Inter-Quartile Range | weeks | four or six months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety population | Posted | Count of Participants | Participants | four or six months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis Population Description: This analysis population includes participants in EFV group 1 who were already on an EFV-containing ART regimen when initiating RPT-based TB treatment (experimental arms only). That is, this analysis was pre-specified to report data by pooling participants from Regimen 2 (2HPZE/2HP) and Regimen 3 (2HPMZ/2HPM) who were on an EFV-containing ART regimen. | Posted | Count of Participants | Participants | four months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | TB Disease-free Survival at Eighteen Months After Study Treatment Assignment |
| 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 | Posted | Count of Participants | Participants | Eighteen months after study treatment assignment. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | TB Disease-free Survival at Eighteen Months After Study Treatment Assignment |
| Assessable Population: Excluded the Microbiologically eligible pts without an assessable outcomes as if they were not already classified as unfavorable and add did not attend mo12 visit but were culture negative when last seen, or had treatment changed due to pregnancy, or died during follow-up with cause unrelated to tuberculosis, or received additional treatment for tuberculosis following exogenous reinfection demonstrated by WGS, or died from a violent or accidental death during treatment | Posted | Count of Participants | Participants | Eighteen months after treatment assignment |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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) | 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. | Posted | Number | log10 DTP / day | 12 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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. | Microbiologically eligible analysis population. | Posted | Count of Participants | Participants | 12 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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. | Assessable analysis population. | Posted | Count of Participants | Participants | 12 months |
|
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)
The Safety analysis population included all the randomized patients and received at least 1 dose of trial medication. Grade 3 or higher Adverse Events per CTCAE V4.03 are collected in systematic way through the laboratory tests and physical exam at regular study visits and also non-systematic way when self-reported by participants. All Cause Mortality is adjusted to reflect the deaths occurred up to M18 study visit.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Regimen 1 (2HRZE/4HR) | 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 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 control: standard six-month treatment | 12 | 825 | 56 | 825 | 74 | 825 |
| EG001 | Regimen 2 (2HPZ/2HP) | 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 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 rifapentine: Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment | 11 | 835 | 39 | 835 | 61 | 835 |
| EG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. | 13 | 846 | 37 | 846 | 94 | 846 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Thrombotic Thrombocytopenic Purpura | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cardiac Failure Congestive | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Myocardial Ischemia | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Right Ventricular Failure | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Diabetic Retinopathy | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Acute Pancreatitis | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pneumatosis Intestinalis | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Small Intestinal Obstruction | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Upper Gastrointestinal Hemorrhage | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Death | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Drug Intolerance | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Bone Tuberculosis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Dengue Fever | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Extrapulmonary Tuberculosis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Hepatitis C | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Orchitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Paracoccidioidal Infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Pneumonia Bacterial | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Pulmonary Tuberculosis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Tuberculosis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Alcohol Poisoning | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Chest Injury | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Craniocerebral Injury | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Documented Hypersensitivity To Administered Product | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Hand Fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Humerus Fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Limb Injury | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Road Traffic Accident | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Stab Wound | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Thermal Burn | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Tibia Fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Traumatic Hemothorax | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
| |
| Electrocardiogram QT Prolonged | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Diabetes Mellitus, Inadequate Control | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Diabetic Ketoacidosis | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Sacroilitis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Anogenital Warts | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Neoplasm, Malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Esophageal Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Papillary Thyroid Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Squamous Cell Carcinoma of Tongue | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Central Nervous System Lesion | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cerebral Infarction | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cerebrovascular Accident | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Guillian-Barre Syndrome | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Seizure | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
| |
| Temporal Lobe Epilepsy | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Complication of Pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (20.0) | Systematic Assessment |
| |
| Pre-Eclampsia | Pregnancy, puerperium and perinatal conditions | MedDRA (20.0) | Systematic Assessment |
| |
| Pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (20.0) | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Suicide Attempt | Psychiatric disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Renal Impairment | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Renal Tubular Necrosis | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Bronchiectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Drug Reaction with Eosinophilia and Systemic Symptoms | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Rash Generalized | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Rash, Maculopapular | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Aortic Thrombosis | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Deep Vein Thrombosis | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
|
A study limitation is that placebos were not used, and therefore neither participants nor site staff were blinded to treatment assignment. Another limitation is that only 8% of participants were HIV-coinfected, limiting the power to compare regimens in this important population
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ekaterina Kurbatova, MD, PhD, MPH | Centers for Disease Control and Prevention | 4046392017 | ies3@cdc.gov |
| Jul 29, 2021 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C018421 | rifapentine |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Africa |
|
| South Asia |
|
| South America |
|
| HIV Positive |
|
| No cavitation on chest radiograph |
|
| Unknown |
|
| Non-Inferiority |
Non-inferiority was assessed using the upper bound of the two-sided 95% CI for the difference between the percentage of patients who are classified as having an unfavorable status on the control regimen (2HRZE/ 4 HR) and the investigational regimens, Regimen 2 (2HPZ/2HP) and Regimen 3 (2HPZM/2HPM). If the upper bound of the confidence interval is less than , then the non-inferiority of Arm 2 or Arm 3 to Arm 1 with a significance level of 0.05 is established (equivalent to one-sided α=0.025). |
| For primary efficacy endpoint, unfavorable outcomes for Arm1(control) vs Arm3(2PHZM/2PHM) will be considered first, if non-inferiority criteria are met, then Arm 1 vs Arm 2(2PHZE/2PH) will be compared. The proportion of participants with unfavorable outcome can be estimated as: if r_a and r_b are the proportions of unfavorable outcome for the two study arms (a=Arm1 and b = Arm2 or Arm3) and if δ is the non-inferiority margin (=6.6%), statistical hypothesis is H_0:r_b-r_a≥δ vs.H_1:r_b-r_a<δ | Cochran-Mantel-Haenszel | For a significance level of 0.05, the statistical test is equivalent to obtaining the two-sided 95% confidence interval for the difference of r_b-r_a. | 0.05 | Risk Difference (RD) | 3 | 2-Sided | 95 | -0.6 | 6.6 | Non-Inferiority | Non-inferiority was assessed using the upper bound of the two-sided 95% CI for the difference between the percentage of patients who are classified as having an unfavorable status on the control regimen (2HRZE/ 4 HR) and the investigational regimens, Regimen 2 (2HPZ/2HP) and Regimen 3 (2HPZM/2HPM). If the upper bound of the confidence interval is less than , then the non-inferiority of Arm 2 or Arm 3 to Arm 1 with a significance level of 0.05 is established (equivalent to one-sided α=0.025). |
| OG001 | Regimen 2 (2HPZ/2HP) | 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 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 rifapentine: Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment |
| OG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
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| OG001 | Regimen 2 (2HPZ/2HP) | 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 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 rifapentine: Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment |
| OG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
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| OG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
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| OG002 | Regimen 3 | 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
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| OG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
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| OG001 | Regimen 2 (2HPZ/2HP) | 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 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 rifapentine: Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment |
| OG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
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| OG001 | Regimen 2 (2HPZ/2HP) | 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 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 rifapentine: Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment |
| OG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
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| OG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
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| OG001 | Regimen 2 (2HPEZ/2HP) | 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 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 rifapentine: Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment |
| OG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
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| OG001 | Regimen 2 (2HPEZ/2HP) | 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 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 rifapentine: Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment |
| OG002 | Regimen 3 (2HPMZ/2HPM) | 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; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg 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 rifapentine and moxifloxacin: Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol. |
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