Substitution of Ethambutol With Linezolid During the Intensive Phase of Treatment of Pulmonary Tuberculosis: A Prospective, Multicenter, Randomized, Open-label Phase II Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 429
- 试验地点
- 3
- 主要终点
- Sputum culture conversion rate on liquid media
研究概览
简要总结
The current standard short-course treatment for pulmonary TB requires 6 months to complete. This long duration of treatment increases the likelihood of side effects while decreasing patients' adherence to anti-TB drugs. Linezolid showed considerable efficacy against refractory multidrug-resistant TB. Considering the marked anti-TB effects of linezolid as well as the possible adverse effects of its long-term use, it is rational to use linezolid instead of ethambutol for the first 4 weeks of treatment for drug-susceptible pulmonary TB. Through randomized controlled trial, the investigators will evaluate the hypothesis that the use of linezolid instead of ethambutol will increase the sputum culture conversion rate by 15% after 2 months of treatment. Patients with TB without resistance to rifampicin will be randomized to the following three arms at a 1:1:1 ratio: Arma 1 (control arm), Arm 2 (linezolid for 2 weeks instead of ethambutol), Arm 3 (linezolid for 4 weeks instead of ethambutol)Primary outcome will be sputum culture conversion rate after 2 months of treatment (liquid media).
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
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females aged from 20 to 80 years (20- and 80-year-old patients can participate).
- •Documented sputum Xpert MTB/RIF assay-positive pulmonary TB at screening.
- •On current TB therapy (if any) for ≤14 days at the time of enrollment.
排除标准
- •Patients with HIV/AIDS.
- •Females of childbearing potential, who are pregnant, breastfeeding, or unwilling to avoid pregnancy.
- •Any of the following:
- •i.Absolute neutrophil count of <2000 cells/mL. ii.White blood cell count (WBC) of <3000/μL. iii.Hemoglobin concentration of <7.0 g/dL. iv.Serum creatinine level of >2.0 mg/dL. v.Aspartate aminotransferase (AST or SGOT) of >100 IU/L. vi.Alanine aminotransferase (ALT or SGPT) of >100 IU/L. vii.Total bilirubin level of >2.0 mg/dL. viii.History of optic neuritis or peripheral neuropathy. ix.Other significant laboratory abnormalities (i.e., absolute neutrophil count, creatinine level).
- •x.The need for ongoing therapy with SSRIs, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine, buspirone, monoamine oxidase inhibitors (MAOIs), sympathomimetic agents (e.g., pseudoephedrine), vasopressive agents (e.g., epinephrine, norepinephrine), or dopaminergic agents (e.g., dopamine, dobutamine).
研究组 & 干预措施
Arm 1 (control arm)
Standard treatment for drug-sensitive pulmonary TB using isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months)
干预措施: Ethambutol (Drug)
Arm 2 (experimental arm 1)
Isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 2 weeks)
干预措施: Linezolid (Drug)
Arm 3 (experimental arm 2)
Isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 4 weeks)
干预措施: Linezolid (Drug)
结局指标
主要结局
Sputum culture conversion rate on liquid media
时间窗: after 2 months of treatment
次要结局
- Sputum culture conversion rate on solid media(after 2 months of treatment)
- Time to sputum culture conversion (liquid and solid media)(During 6 months of treatment)
- Cure rate(After 6 months of treatment)
- Treatment success rate(after 6 months of treatment)
研究者
Jae-Joon Yim
Professor
Seoul National University Hospital