Delamanid, Linezolid, Levofloxacin, and Pyrazinamide for the Treatment of Patients With Fluoroquinolone-sensitive MDR-TB: A Phase 2/3, Multicenter, Randomized, Open-label, Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 214
- 试验地点
- 1
- 主要终点
- Treatment Success Rate
研究概览
简要总结
The purpose of this study is to compare the efficacy of a 'new treatment regimen including delamanid, linezolid, levofloxacin, and pyrazinamide for nine or twelve months (investigational arm)' and 'the standard treatment regimen including injectables for 20 to 24 months (control arm)' for treating fluoroquinolone-sensitive multidrug-resistant tuberculosis.
详细描述
This study is a phase II/III, multicenter, randomized, open-label clinical trial of non-inferiority design comparing a new regimen to the World Health Organization-endorsed conventional regimen for fluoroquinolone-sensitive MDR-TB. The control arm uses a conventional treatment regimen with second-line drugs including injectables for 20-24 months. The investigational arm uses a new shorter regimen including delamanid, linezolid, levofloxacin, and pyrazinamide for 9 or 12 months depending on time to sputum culture conversion. The primary outcome is the treatment success rate at 24 months after treatment initiation. Secondary outcomes include time to sputum culture conversion on liquid and solid media, proportions of sputum culture conversion on liquid media after 2 and 6 months of treatment, treatment success rate according to pyrazinamide resistance, and occurrence of adverse events grade 3 and above as evaluated by the Common Terminology Criteria for Adverse Events. The population number is calculated as 102 per group (204 in total).
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
- 19 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females aged from 19 to 85 years
- •Confirmed MDR-TB or RR-TB
- •On current TB therapy for ≤14 days at the time of enrollment.
排除标准
- •Known any quinolone-resistant MDR-TB
- •Known XDR-TB
- •who are pregnant or who are unwilling to use proper contraceptives at childbearing age
- •Medical history of galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption
- •The need for ongoing use of prohibited drugs while on study drugs
- •History of optic neuropathy or peripheral neuropathy
- •With any of the following test results: i.Absolute neutrophil count < 2000 cells/mL, ii.White blood cell count (WBC) < 3.0 X 103/µL, iii.Hemoglobin < 7.0 g/dL, iv.Serum creatinine > 2.0 mg/dL, v.Aspartate aminotransferase (AST or SGOT) >100 IU/L, vi.Alanine aminotransferase (ALT or SGPT) >100 IU/L, vii.Total bilirubin > 2.0 mg/dL, viii.Albumin < 2.8g/dL, ix.QTcF > 500ms
- •History of hypersensitivity reaction to the study drugs
研究组 & 干预措施
Control Arm
Regimen is the locally-used WHO-approved MDR-TB regimen in Korea based on 2014 Korean guideline of TB management.
- Intensive phase regimen consists of four effective second-line anti-TB drugs (including injectables) and pyrazinamide.
- Treatment duration: for at least 20 months
干预措施: Locally-used WHO-approved MDR-TB regimen in Korea (Drug)
Experimental Arm
Regimen consists of only oral medication using delamanid, linezolid, levofloxacin, and pyrazinamide, for nine or twelve months depending on the time of sputum culture conversion to negative.
- Delamanid (100 mg bid for the entire treatment period)
- Linezolid (600mg/day for 2 months and 300mg/day afterwards until the end of treatment)
- Levofloxacin (750 ~1000 mg/day)
- Pyrazinamide (1000~ 2000 mg/day)
干预措施: Linezolid (Drug)
Experimental Arm
Regimen consists of only oral medication using delamanid, linezolid, levofloxacin, and pyrazinamide, for nine or twelve months depending on the time of sputum culture conversion to negative.
- Delamanid (100 mg bid for the entire treatment period)
- Linezolid (600mg/day for 2 months and 300mg/day afterwards until the end of treatment)
- Levofloxacin (750 ~1000 mg/day)
- Pyrazinamide (1000~ 2000 mg/day)
干预措施: Delamanid (Drug)
Experimental Arm
Regimen consists of only oral medication using delamanid, linezolid, levofloxacin, and pyrazinamide, for nine or twelve months depending on the time of sputum culture conversion to negative.
- Delamanid (100 mg bid for the entire treatment period)
- Linezolid (600mg/day for 2 months and 300mg/day afterwards until the end of treatment)
- Levofloxacin (750 ~1000 mg/day)
- Pyrazinamide (1000~ 2000 mg/day)
干预措施: Levofloxacin (Drug)
Experimental Arm
Regimen consists of only oral medication using delamanid, linezolid, levofloxacin, and pyrazinamide, for nine or twelve months depending on the time of sputum culture conversion to negative.
- Delamanid (100 mg bid for the entire treatment period)
- Linezolid (600mg/day for 2 months and 300mg/day afterwards until the end of treatment)
- Levofloxacin (750 ~1000 mg/day)
- Pyrazinamide (1000~ 2000 mg/day)
干预措施: Pyrazinamide (Drug)
结局指标
主要结局
Treatment Success Rate
时间窗: 24 months after treatment start
To test for non-inferiority of the investigational arm, when the lower limit of the one-sided 97.5% confidence interval of the difference (PT - PC) between investigational and control arms is larger than the non-inferiority margin of - 10%, it will be concluded that the treatment success rate of the investigational arm shows non-inferiority to the treatment success rate of the control arm. (primary consideration for the modified intention-to-treat results)
次要结局
- Time to Sputum Culture Conversion After Treatment Start(through study completion (24 months after treatment start))
- Sputum Culture Conversion Proportion(At 6 months of treatment start)
- Treatment Success at the End of Treatment(At the end of treatment)
- Proportion of Reverting to Positive Sputum Culture After the End of Treatment(At 24months after treatment start)
- Treatment Success According to Pyrazinamide Resistance (1)(At 24months after treatment start)
- Proportion of Death Between the Control and Investigational Arms(At 24months after treatment start)
- Treatment Success According to Pyrazinamide Resistance (2)(At 24 months after treatment start)
研究者
Jae-Joon Yim
Professor
Seoul National University Hospital