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Tuberculosis (TB) remains the most important infectious disease in the world. A major barrier to tuberculosis control is poor adherence to long-term and complex treatment regimens.
This is a multicenter prospective, non-inferiority randomized controlled study. The purpose of our study is a) to evaluate the tolerability, efficacy and pharmacokinetics/pharmacodynamics (PK/PD) of the high-dose rifapentine, b) to evaluate whether the high-dose rifapentine-containing regimen has the potential to treat the rifampicin-sensitive pulmonary tuberculosis and shorten the course of treatment to 17 weeks. This study is of great significance for shortening the course of treatment, reducing the adverse reactions and economic burden of patients' treatment in rifampicin-sensitive tuberculosis patient.
Tuberculosis (TB) remains the most important infectious disease in the world. A major barrier to tuberculosis control is poor adherence to long-term and complex treatment regimens. Incomplete TB treatment can lead to increased morbidity and mortality, prolonged infectivity and transmission, and the development of drug resistance. The development of new therapeutic strategies with stronger bactericidal activity could lead to shorter and better-tolerated regimens, thereby increasing cure rates, lowering costs, potentially reducing transmission and preventing the emergence of multidrug-resistant tuberculosis (MDR-TB).
This trial is a multicenter prospective, non-inferiority randomized controlled study. Rifampicin-sensitive pulmonary tuberculosis patients will be included in our study. Stage 1 of the study is designed to evaluate the tolerability, efficacy and PK/PD of the high-dose rifapentine in order to select two doses to carry forward into study Stage 2. Study Stage 2 will provide pivotal confirmation of efficacy, safety, and tolerability of the selected rifapentine doses in patients with rifampicin-sensitive pulmonary tuberculosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Short Regimen with Rifapentine 10mg/kg | Experimental | Intervention: Short Regimen with Rifapentine 10mg/kg consists of two periods of 17- 26 weeks. The first is an intensive phase of 8 weeks, and included rifapentine, isoniazid, pyrazinamide, and moxifloxacin. This is followed by a continuation phase of 9 weeks with the following agents: rifapentine, isoniazid and moxifloxacin (extended up a maximum of 18 weeks if no smear conversion at the end of 8 weeks or the tuberculosis cavity is not closed at the end of 17 weeks). |
|
| Short Regimen with Rifapentine 15mg/kg | Experimental | Intervention: Short Regimen with Rifapentine 15mg/kg consists of two periods of 17- 26 weeks. The first is an intensive phase of 8 weeks, and included rifapentine, isoniazid, pyrazinamide, and moxifloxacin. This is followed by a continuation phase of 9 weeks with the following agents: rifapentine, isoniazid and moxifloxacin (extended up a maximum of 18 weeks if no smear conversion at the end of 8 weeks or the tuberculosis cavity is not closed at the end of 17 weeks). |
|
| Standardized Regimen | Active Comparator | Intervention:World Health Organization (WHO) Standardized Regimen group consists of 26 weeks with two phases of treatment. The first is an intensive phase of 8 weeks, and included rifampicin, isoniazid, pyrazinamide, and ethambutol. This is followed by a continuation phase of 18 weeks with the following agents: rifampicin and isoniazid. |
|
| Short Regimen with Rifapentine 20mg/kg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Short Regimen with Rifapentine 10mg/kg | Other | rifapentine 10mg/kg daily; isoniazid 300mg daily; pyrazinamide ≤50kg 1000mg daily, 50-71kg 1200mg daily, >71kg 1000mg daily; moxifloxacin 400mg daily. All treatment is taken orally. |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment success rate of the short regimen during drug treatment and follow-up. | To compare the treatment success rate without relapse between the short regimen with rifapentine 10mg/kg, the short regimen with rifapentine 15mg/kg, the short regimen with rifapentine 20mg/kg and the WHO standardized regimen group. | 108 weeks after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| The frequency of grade 3 or greater adverse events among patients Over the 108 Week Treatment and Follow-up Period. | To compare the proportion of patients who experience grade 3 or greater adverse events between the short regimen with rifapentine 10mg/kg, the short regimen with rifapentine 15mg/kg, the short regimen with rifapentine 20mg/kg and the WHO standardized regimen group. | up to 108 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Feng Sun, Dr. | Contact | (086)15921403893 | 8123 | aaronsf1125@126.com |
| Yang Li, Dr. | Contact | (086)18817583793 | 8123 | y_li11@fudan.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Wenhong Zhang, PhD. | Huashan Hospital of Fudan University,Shanghai,China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Guiyang Public Health Clinical Center | Not yet recruiting | Guiyang | Guizhou | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37158831 | Derived | Feng Z, Miao Y, Peng Y, Sun F, Zhang Y, Li R, Ge S, Chen X, Song L, Li Y, Wang X, Zhang W. Optimizing (O) rifapentine-based (RI) regimen and shortening (EN) the treatment of drug-susceptible tuberculosis (T) (ORIENT) using an adaptive seamless design: study protocol of a multicenter randomized controlled trial. BMC Infect Dis. 2023 May 8;23(1):300. doi: 10.1186/s12879-023-08264-2. |
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Intervention: Short Regimen with Rifapentine 20mg/kg consists of two periods of 17- 26 weeks. The first is an intensive phase of 8 weeks, and included rifapentine, isoniazid, pyrazinamide, and moxifloxacin. This is followed by a continuation phase of 9 weeks with the following agents: rifapentine, isoniazid and moxifloxacin (extended up a maximum of 18 weeks if no smear conversion at the end of 8 weeks or the tuberculosis cavity is not closed at the end of 17 weeks). |
|
| Standardized Regimen | Combination Product | During the intensive phase, rifampicin ≤55kg 450mg daily, 55-71kg 600mg daily, >71kg 750mg daily; isoniazid ≤55kg 225mg daily, 55-71kg 300mg daily, >71kg 375mg daily; pyrazinamide ≤55kg 900mg daily, 55-71kg 1200mg daily, >71kg 1600mg daily; ethambutol ≤55kg 825mg daily, 55-71kg 1100mg daily, >71kg 1375mg daily; All treatment is taken orally. During the continuation phase, rifampicin ≤50kg 450mg daily, >50kg 600mg daily; isoniazid 300mg daily; All treatment is taken orally. |
|
| Short Regimen with Rifapentine 15mg/kg | Other | rifapentine 15mg/kg daily; isoniazid 300mg daily; pyrazinamide ≤50kg 1000mg daily, 50-71kg 1200mg daily, >71kg 1000mg daily; moxifloxacin 400mg daily. All treatment is taken orally. |
|
| Short Regimen with Rifapentine 20mg/kg | Other | rifapentine 20mg/kg daily; isoniazid 300mg daily; pyrazinamide ≤50kg 1000mg daily, 50-71kg 1200mg daily, >71kg 1000mg daily; moxifloxacin 400mg daily. All treatment is taken orally. |
|
| Relapse rate during follow-up. | To compare the treatment success rate without relapse between the short regimen with rifapentine 10mg/kg, the short regimen with rifapentine 15mg/kg, the short regimen with rifapentine 20mg/kg and the WHO standardized regimen group. | 82-91 weeks after the end of drug treatment. |
| the percentage of participants found to be culture-negative at the end of intensive phase and the end of treatment phase | To compare the percentage of participants found to be culture-negative at the end of intensive phase and the end of treatment phase between the short regimen with rifapentine 10mg/kg, the short regimen with rifapentine 15mg/kg, the short regimen with rifapentine 20mg/kg and the WHO standardized regimen group. | 8 weeks, 17 weeks and 26 weeks after randomization |
| People's Hospital of Qiandongnan | Not yet recruiting | Kaili | Guizhou | China |
|
| The Third People's Hospital of Liupanshui | Not yet recruiting | Liupanshui | Guizhou | China |
|
| Affiliated Hospital of Zunyi Medical University | Not yet recruiting | Zunyi | Guizhou | China |
|
| Department of Infectious Disease, Huashan Hospital | Recruiting | Shanghai | Shanghai Municipality | 200040 | China |
|
| People's Hospital of Zhuji, Zhejiang Province | Not yet recruiting | Zhuji | Zhejiang | 311899 | China |
|
| ID | Term |
|---|---|
| D014397 | Tuberculosis, Pulmonary |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C018421 | rifapentine |
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