Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Clinical Center On TB, Beijing Chest Hospital, Capital Medical University/ Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
BMC Med. 2024 Sep 19;22(1):401. doi: 10.1186/s12916-024-03633-3.
We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China.
This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012.
Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116).
The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.
我们同时开展了一项前瞻性研究，旨在评估接受 9 个月贝达喹啉（BDQ）方案治疗的患者的临床结局，为中国应用这种短程方案提供有价值的数据。
这是一项在 16 家医院开展的开放性、随机、对照、多中心、非劣效性试验，纳入了年龄在 18 岁及以上、患有肺部利福平/多种药物结核病的参与者。参与者按照 1:1 的比例随机分组。标准方案组接受 6 个月的 BDQ、利奈唑胺、左氧氟沙星、氯法齐明和环丝氨酸，以及 12 个月的左氧氟沙星，以及从氯法齐明、环丝氨酸、吡嗪酰胺、乙胺丁醇和丙硫异烟胺中任选三种有效的药物；短程方案组接受 9 个月的 BDQ、利奈唑胺、左氧氟沙星、氯法齐明和环丝氨酸。主要结局是在修改后的意向治疗人群中，随机分组后治疗结束时复合不良结局（治疗失败、死亡、治疗中断或失访）的参与者比例。非劣效性边界为 10%。这项试验在中国临床试验注册中心（www.chictr.org.cn）注册，注册号为 ChiCTR2000029012。
2020 年 1 月 1 日至 2023 年 12 月 31 日期间，共筛选了 264 名参与者，随机分配了 264 名参与者中的 132 名进入标准方案组，132 名进入短程方案组。264 名参与者中有 33 名（12.55%）被排除在修改后的意向治疗分析之外。因此，231 名参与者被纳入修改后的意向治疗分析（标准方案组 116 名，短程方案组 115 名）。在修改后的意向治疗人群中，短程方案组可评估的 115 名参与者中有 19 名（16.5%）出现不良结局，标准方案组 116 名参与者中有 26 名（22.4%）（风险差 5.9 个百分点（97.5%CI -5.8 至 17.5））。标准方案组有 1 例死亡。短程方案组（22.6%，26/115）QTcF 延长的发生率与标准方案组（24.1%，28/116）相似。
9 个月的全口服方案治疗肺部利福平/耐多药结核病安全有效。BDQ 相关的 QTc 延长发生率较高，这突显了在中国人群中应用 BDQ 方案时，常规心电图监测的迫切需要。
