Clinical Center On TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People's Republic of China.
Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China.
Trials. 2024 Apr 1;25(1):227. doi: 10.1186/s13063-024-07946-9.
The lack of safe, effective, and simple short-course regimens (SCRs) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment has significantly impeded TB control efforts in China.
This phase 4, randomized, open-label, controlled, non-inferiority trial aims to assess the efficacy and safety of a 9-month all-oral SCR containing bedaquiline (BDQ) versus an all-oral SCR without BDQ for adult MDR-TB patients (18-65 years) in China. The trial design mainly mirrors that of the "Evaluation of a Standardized Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB" (STREAM) stage 2 study, while also incorporating programmatic data from South Africa and the 2019 consensus recommendations of Chinese MDR/RR-TB treatment experts. Experimental arm participants will receive a modified STREAM regimen C that replaces three group C drugs, ethambutol (EMB), pyrazinamide (PZA), and prothionamide (PTO), with two group B drugs, linezolid (LZD) and cycloserine (CS), while omitting high-dose isoniazid (INH) for confirmed INH-resistant cases. BDQ duration will be extended from 6 to 9 months for participants with Mycobacterium tuberculosis-positive sputum cultures at week 16. The control arm will receive a modified STREAM regimen B without high-dose INH and injectable kanamycin (KM) that incorporates experimental arm LZD and CS dosages, treatment durations, and administration methods. LZD (600 mg) will be given daily for ≥ 24 weeks as guided by observed benefits and harm. The primary outcome measures the proportion of participants with favorable treatment outcomes at treatment completion (week 40), while the same measurement taken at 48 weeks post-treatment completion is the secondary outcome. Assuming an α = 0.025 significance level (one-sided test), 80% power, 15% non-inferiority margin, and 10% lost to follow-up rate, each arm requires 106 participants (212 total) to demonstrate non-inferiority.
PROSPECT aims to assess the safety and efficacy of a BDQ-containing SCR MDR-TB treatment at seventeen sites across China, while also providing high-quality data to guide SCRs administration under the direction of the China National Tuberculosis Program for MDR-TB. Additionally, PROSPECT will explore the potential benefits of extending the administration of the 9-month BDQ-containing SCR for participants without sputum conversion by week 16.
ClinicalTrials.gov NCT05306223. Prospectively registered on 16 March 2022 at https://clinicaltrials.gov/ct2/show/NCT05306223?term=NCT05306223&draw=1&rank=1 {2}.
缺乏安全、有效且简单的短程治疗方案（SCRs）来治疗耐多药/利福平耐药结核病（MDR/RR-TB），这极大地阻碍了中国的结核病控制工作。
本 4 期、随机、开放标签、对照、非劣效性试验旨在评估含有贝达喹啉（BDQ）的 9 个月全口服 SCR 与不含 BDQ 的全口服 SCR 治疗中国成年 MDR-TB 患者（18-65 岁）的疗效和安全性。试验设计主要模仿了“评估耐多药结核病患者标准化治疗方案”（STREAM）第 2 阶段研究，同时纳入了南非的项目数据和中国耐多药/利福平耐药结核病治疗专家 2019 年共识建议。实验组参与者将接受改良的 STREAM 方案 C，用两种 B 组药物（利福喷丁[LZD]和环丝氨酸[CS]）替代 C 组的三种药物（乙胺丁醇[EMB]、吡嗪酰胺[PZA]和丙硫异烟胺[PTO]），对于确认 INH 耐药的病例，不使用高剂量异烟肼（INH）。对于第 16 周痰培养阳性的患者，BDQ 疗程将从 6 个月延长至 9 个月。对照组将接受改良的 STREAM 方案 B，不使用高剂量 INH 和注射用卡那霉素（KM），该方案包含实验组的 LZD 和 CS 剂量、治疗持续时间和给药方法。LZD（600mg）将根据观察到的益处和危害，每日给药至少 24 周。主要终点是治疗结束时（第 40 周）参与者治疗结果良好的比例，次要终点是治疗结束后 48 周的相同测量结果。假设 α=0.025 显著性水平（单侧检验）、80%效力、15%非劣效性边界和 10%失访率，每个组需要 106 名参与者（共 212 名）来证明非劣效性。
PROSPECT 旨在评估含 BDQ 的 SCR MDR-TB 治疗在中国 17 个地点的安全性和疗效，同时提供高质量的数据，以指导国家结核病规划在 MDR-TB 下管理 SCR。此外，PROSPECT 将探索对于第 16 周痰培养未转阴性的患者，延长使用 9 个月含 BDQ 的 SCR 的潜在益处。
ClinicalTrials.gov NCT05306223。于 2022 年 3 月 16 日在 https://clinicaltrials.gov/ct2/show/NCT05306223？term=NCT05306223&draw=1&rank=1[2]前瞻性注册。
