A Pragmatic Randomized Controlled Trial to Evaluate the Efficacy and Safety of an Oral Short-course Regimen Including Bedaquiline for the Treatment of Patients With Multidrug-resistant Tuberculosis in China
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 212
- 试验地点
- 17
- 主要终点
- Percentage of Participants with a Favorable Treatment Outcome at the End of Treatment
研究概览
简要总结
The purpose of this study is to evaluate efficacy and safety of an oral bedaquiline-containing multidrug-resistant tuberculosis (MDR-TB) short-course regimen (SCR) compared to an oral SCR not including bedaquiline at the end of treatment in participants with pulmonary MDR-TB in China.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a positive sputum Mycobacterium tuberculosis culture from a test performed at screening
- •Has microbiological confirmation of rifampicin resistance by GeneXpert and to isoniazid (INH) via molecular drug-susceptibility testing (DST) showing katG mutation
- •Has a chest imaging result compatible with a diagnosis of pulmonary Tuberculosis (TB)
- •Agrees to use effective contraception during the 40-week study treatment phase. A female participant must be: of nonchildbearing potential; of childbearing potential and practicing effective methods of contraception during the 40-week study treatment phase
- •Is willing to undergo human immunodeficiency virus (HIV) testing
排除标准
- •Has received prior treatment with bedaquiline
- •Has prior exposure to at least 1 second-line drug in the regimen for at least 4 weeks
- •Has any grade 3 or 4 laboratory abnormality as confirmed by a clinical expert
- •Has a known allergy or intolerance to bedaquiline or other drugs in the regimen
- •Is infected with a strain of nontuberculous mycobacteria
- •Is HIV-positive
研究组 & 干预措施
Bedaquiline-containing Short-course Regimen (SCR)
Participants will receive an oral dose of bedaquiline 400 milligrams (mg) once daily for first 2 weeks followed by bedaquiline 200 mg thrice a week for 22 weeks (with at least 48 hours between doses) in combination with oral doses of levofloxacin (LFX) up to 1000 mg (weight-based), cycloserine (CS) up to 750 mg (weight-based), clofazimine (CFZ) 100 mg daily for 40 weeks and linezolid [LZD] 600 mg daily for at least 24 weeks . If a participant is still sputum culture-positive for Mycobacterium tuberculosis by Week 16, bedaquiline treatment will be extended from Week 24 to Week 40.
干预措施: Bedaquiline (Drug)
Bedaquiline-containing Short-course Regimen (SCR)
Participants will receive an oral dose of bedaquiline 400 milligrams (mg) once daily for first 2 weeks followed by bedaquiline 200 mg thrice a week for 22 weeks (with at least 48 hours between doses) in combination with oral doses of levofloxacin (LFX) up to 1000 mg (weight-based), cycloserine (CS) up to 750 mg (weight-based), clofazimine (CFZ) 100 mg daily for 40 weeks and linezolid [LZD] 600 mg daily for at least 24 weeks . If a participant is still sputum culture-positive for Mycobacterium tuberculosis by Week 16, bedaquiline treatment will be extended from Week 24 to Week 40.
干预措施: Levofloxacin (Drug)
Bedaquiline-containing Short-course Regimen (SCR)
Participants will receive an oral dose of bedaquiline 400 milligrams (mg) once daily for first 2 weeks followed by bedaquiline 200 mg thrice a week for 22 weeks (with at least 48 hours between doses) in combination with oral doses of levofloxacin (LFX) up to 1000 mg (weight-based), cycloserine (CS) up to 750 mg (weight-based), clofazimine (CFZ) 100 mg daily for 40 weeks and linezolid [LZD] 600 mg daily for at least 24 weeks . If a participant is still sputum culture-positive for Mycobacterium tuberculosis by Week 16, bedaquiline treatment will be extended from Week 24 to Week 40.
干预措施: Linezolid (Drug)
Bedaquiline-containing Short-course Regimen (SCR)
Participants will receive an oral dose of bedaquiline 400 milligrams (mg) once daily for first 2 weeks followed by bedaquiline 200 mg thrice a week for 22 weeks (with at least 48 hours between doses) in combination with oral doses of levofloxacin (LFX) up to 1000 mg (weight-based), cycloserine (CS) up to 750 mg (weight-based), clofazimine (CFZ) 100 mg daily for 40 weeks and linezolid [LZD] 600 mg daily for at least 24 weeks . If a participant is still sputum culture-positive for Mycobacterium tuberculosis by Week 16, bedaquiline treatment will be extended from Week 24 to Week 40.
干预措施: Cycloserine (Drug)
Bedaquiline-containing Short-course Regimen (SCR)
Participants will receive an oral dose of bedaquiline 400 milligrams (mg) once daily for first 2 weeks followed by bedaquiline 200 mg thrice a week for 22 weeks (with at least 48 hours between doses) in combination with oral doses of levofloxacin (LFX) up to 1000 mg (weight-based), cycloserine (CS) up to 750 mg (weight-based), clofazimine (CFZ) 100 mg daily for 40 weeks and linezolid [LZD] 600 mg daily for at least 24 weeks . If a participant is still sputum culture-positive for Mycobacterium tuberculosis by Week 16, bedaquiline treatment will be extended from Week 24 to Week 40.
干预措施: Clofazimine (Drug)
Non-bedaquiline-containing Short-course Regimen (SCR)
Participants will receive oral doses of LFX up to 1000 mg (weight-based), CS up to 750 mg (weight-based), CFZ 100 mg, Pyrazinamide (PZA) up to 2000 mg (weight-based), Protionamide (PTO) up to 800 mg (weight-based) daily for first 16 weeks and LZD 600 mg daily for at least 24 weeks.
干预措施: Levofloxacin (Drug)
Non-bedaquiline-containing Short-course Regimen (SCR)
Participants will receive oral doses of LFX up to 1000 mg (weight-based), CS up to 750 mg (weight-based), CFZ 100 mg, Pyrazinamide (PZA) up to 2000 mg (weight-based), Protionamide (PTO) up to 800 mg (weight-based) daily for first 16 weeks and LZD 600 mg daily for at least 24 weeks.
干预措施: Linezolid (Drug)
Non-bedaquiline-containing Short-course Regimen (SCR)
Participants will receive oral doses of LFX up to 1000 mg (weight-based), CS up to 750 mg (weight-based), CFZ 100 mg, Pyrazinamide (PZA) up to 2000 mg (weight-based), Protionamide (PTO) up to 800 mg (weight-based) daily for first 16 weeks and LZD 600 mg daily for at least 24 weeks.
干预措施: Cycloserine (Drug)
Non-bedaquiline-containing Short-course Regimen (SCR)
Participants will receive oral doses of LFX up to 1000 mg (weight-based), CS up to 750 mg (weight-based), CFZ 100 mg, Pyrazinamide (PZA) up to 2000 mg (weight-based), Protionamide (PTO) up to 800 mg (weight-based) daily for first 16 weeks and LZD 600 mg daily for at least 24 weeks.
干预措施: Clofazimine (Drug)
Non-bedaquiline-containing Short-course Regimen (SCR)
Participants will receive oral doses of LFX up to 1000 mg (weight-based), CS up to 750 mg (weight-based), CFZ 100 mg, Pyrazinamide (PZA) up to 2000 mg (weight-based), Protionamide (PTO) up to 800 mg (weight-based) daily for first 16 weeks and LZD 600 mg daily for at least 24 weeks.
干预措施: Pyrazinamide (Drug)
Non-bedaquiline-containing Short-course Regimen (SCR)
Participants will receive oral doses of LFX up to 1000 mg (weight-based), CS up to 750 mg (weight-based), CFZ 100 mg, Pyrazinamide (PZA) up to 2000 mg (weight-based), Protionamide (PTO) up to 800 mg (weight-based) daily for first 16 weeks and LZD 600 mg daily for at least 24 weeks.
干预措施: Protionamide (Drug)
结局指标
主要结局
Percentage of Participants with a Favorable Treatment Outcome at the End of Treatment
时间窗: At the end of treatment (Week 40)
Percentage of participants with a favorable treatment outcome at the end of treatment will be reported. A participant's outcome will be classified as favorable if their last 3 culture results by the end of treatment are negative unless they have previously been classified as unfavorable. These 3 cultures must be taken on separate visits; the latest of which being no more than 8 weeks prior to the end of treatment.
次要结局
- Percentage of Participants with a Favorable Treatment Outcome at 48 Weeks Post the End of Treatment(At 48 weeks post the end of treatment (Week 88))
- Percentage of Participants Achieving Treatment Success at the end of Treatment(At the end of treatment (Week 40))
- Percentage of Participants Whose Isolates Develop Resistance to Bedaquiline and Other Drugs Used in the Regimen(Up to Week 88)
- Percentage of Participants with a Modified Favorable Treatment Outcome at the end of Treatment and at 48 Weeks Post end of Treatment(At the end of treatment (Week 40) and at 48 weeks post end of treatment (Week 88))
- Percentage of Participants Experiencing TEAEs(From Week 1 up to Week 88)
- Percentage of Participants with TB Relapses and Re-infections During the Treatment-free Follow-up Phase(During the treatment-free follow-up phase (Up to 48 weeks))
- Percentage of Participants Experiencing All-cause Mortality(Up to Week 88)
- Percentage of Participants Experiencing Grade 3 or Greater Treatment-emergent Adverse Events (TEAEs) During Study Treatment and Follow-up(During study treatment and follow-up (From Week 1 up to Week 88))
研究者
Gao Mengqiu
Director of Department of Tuberculosis
Beijing Chest Hospital