Innovating(IN) Shorter(S), All- Oral, Precised(P), Individualized(I) Treatment Regimen(RE) for Rifampicin Resistant Tuberculosis(INSPIRE-TB)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,050
- 试验地点
- 5
- 主要终点
- a favorable outcome at the end of study
研究概览
简要总结
The INSPIRE-TB study is a pragmatic, multicentre, randomised, controlled, non-inferiority open-label trial to evaluate the efficacy and safety of seven 9-month oral regimens compared to a 9-month standard of care (SOC) regimen in RR-TB participants susceptible to fluoroquinolones, and a bedaquiline-containing 9-month oral regimen compared to a 20-month conventional regimen in RR-TB participants resistant to fluoroquinolones
详细描述
RR-TB patients susceptible to fluoroquinolones are identified with the Xpert MTB/XDR assay (Cepheid; Sunnyvale, CA, USA). Experimental arms are seven oral regimens with a five-drug combination of the following: bedaquiline, linezolid, a fluoroquinolone (moxifloxacin or levofloxacin), cycloserine, clofazimine, and pyrazinamide.To minimize potential toxicity, each regimen includes no more than two major QT-prolonging drugs (bedaquiline, clofazimine, and moxifloxacin). Treatment duration of the experimental regimens is 9 months. A 2-month extension of treatment is allowed with the presence of cavities at month 9 or in case of a positive culture at month 2. Baseline molecular drug susceptibility test (DST) of pyrazinamide will be performed using whole gene sequencing (WGS) technique. The result of molecular DST of pyrazinamide will be interpreted by technical staff at central laboratory of Huashan Hospital, Fudan University. Once a participant is proved resistant to pyrazinamide by WGS results at baseline, pyrazinamide will be discontinued with no need for extra drug replacement. The control regimen for RR-TB patients susceptible to fluoroquinolones is the current SOC oral regimen recommended by the national guidelines.
Pre-XDR TB patients are identified with the Xpert MTB/XDR assay. The experimental arm is a 9-month regimen consisting of bedaquiline, cycloserine, clofazimine, linezolid, and pyrazinamide. Treatment extension to 11 months is allowed with the presence of cavities at month 9 or in case of a positive culture at month 2. Pyrazinamide will be discontinued from the study regimen if baseline molecular DST results reveal pyrazinamide resistance. The comparator is a conventional longer regimen (20 months) consistent with the national guidelines.
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
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients aged 16-75 years with weight over 30kg, regardless of HIV status;
- •Pulmonary TB with rifampicin resistance diagnosed with either WHO-approved rapid molecular diagnostic test or phenotype drug susceptibility test (within 60 days prior to randomisation) ;
- •Signed informed consent form (ICF).
排除标准
- •Known allergies, hypersensitivity, or contraindication to any of the study drugs as described in additional material;
- •Participants combined with central nervous system TB, tuberculous osteomyelitis or arthritis, hematogenous disseminated pulmonary TB;
- •Patients known to be pregnant or breastfeeding at the time of enrollment;
- •Patients who have received second-line MDR-TB treatment for 14 days or more prior to enrollment;
- •Patients in critical condition and expected survival is estimated by physician to be less than 12 weeks.
结局指标
主要结局
a favorable outcome at the end of study
时间窗: at 21 months after randomization
A favorable outcome is defined by the absence of previous unfavorable, and the last two culture results are negative. These two cultures must be taken from respiratory samples collected on separate visits at least 7 days apart. The latest culture sample should be collected between month 21 and 23.
次要结局
- The median time to sputum culture conversion(at 21 months after randomization)
- The proportion of participants with grade 3 or higher AEs, SAEs(at 21 months after randomization)
- All-cause mortality and treatment relevant mortality(at 21 months after randomization)
- The proportion of participants with treatment relevant SAEs(at 21 months post-randomization)
- The proportion of participants with grade 3 or higher QTc prolongation(at 21 months after randomization)
- The proportion of participants experiencing permanent drug discontinuation or replacement due to QTc prolongation(at 21 months after randomization)
研究者
Wen-hong Zhang
Director of Division of Infectious Diseases
Huashan Hospital