Nine months of bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine chemotherapy for rifampicin/multidrug-resistant tuberculosis: a multicenter, randomized, open-label non-inferiority trial in China (vol 22, 401, 2024)

被引：0

作者：

Song, Yanhua ^{[1
]}

Shu, Wei ^{[2
]}

Pei, Yi ^{[3
]}

Du, Juan ^{[4
]}

Wu, Guihui ^{[5
]}

Wang, Hua ^{[6
]}

Mi, Fengling ^{[7
]}

Liu, Fangchao ^{[7
]}

Ma, Liping ^{[1
]}

Xie, Li ^{[1
]}

Kong, Zhongshun ^{[1
]}

Wu, Xiaoguang ^{[1
]}

Liu, Rongmei ^{[1
]}

Chen, Hongmei ^{[1
]}

Li, Hua ^{[1
]}

Ge, Qiping ^{[1
]}

Nie, Lihui ^{[1
]}

Lv, Zizheng ^{[1
]}

Huang, Xuerui ^{[1
]}

Li, Mingwu ^{[8
]}

Jiang, Mingying ^{[9
]}

Chen, Xiaohong ^{[10
]}

Cai, Qingshan ^{[11
]}

Chen, Wei ^{[12
]}

Liu, Yanmei ^{[13
]}

Miao, Yanfang ^{[14
]}

Tang, Yan ^{[15
]}

Chen, Yu ^{[16
]}

Geng, Shujun ^{[17
]}

Zhou, Quanying ^{[18
]}

Liu, Yuhong ^{[2
]}

Pang, Yu ^{[19
]}

Gao, Mengqiu ^{[1
]}

机构：

[1] Capital Med Univ, Beijing Chest Hosp, Beijing TB & Thorac Tumor Res Inst, Dept TB, Beijing, Peoples R China

[2] Capital Med Univ, Beijing Chest Hosp, Beijing TB & Thorac Tumor Res Inst, Clin Ctr TB, Beijing, Peoples R China

[3] Changsha Cent Hosp, Dept TB, Changsha, Peoples R China

[4] Wuhan Pulm Hosp, Dept TB, Wuhan, Peoples R China

[5] Chengdu Publ Hlth Clin Ctr, Dept TB, Chengdu, Peoples R China

[6] Anhui Chest Hosp, Dept TB, Hefei, Peoples R China

[7] Capital Med Univ, Beijing Chest Hosp, Beijing TB & Thorac Tumor Inst, Sci & Technol Off, Beijing, Peoples R China

[8] Third Peoples Hosp Kunming, Dept TB, Kunming, Peoples R China

[9] Chongqing Publ Hlth Med Ctr, Dept TB, Chongqing, Peoples R China

[10] Fuzhou Pulm Hosp, Dept TB, Fuzhou, Peoples R China

[11] Hangzhou Red Cross Hosp, Dept TB, Hangzhou, Peoples R China

[12] Shenyang Tenth Peoples Hosp, Dept TB, Shenyang, Peoples R China

[13] TB Hosp Jilin Prov, Dept TB, Changchun, Peoples R China

[14] Forth Peoples Hosp Taiyuan, Dept TB, Taiyuan, Peoples R China

[15] Shaanxi Prov TB Prevent & Control Hosp, Dept TB, Xian, Peoples R China

[16] Henan Prov Infect Dis Hosp, Dept TB, Zhengzhou, Peoples R China

[17] Hebei Chest Hosp, Dept TB, Shijiazhuang, Peoples R China

[18] Lanzhou Pulm Hosp, Dept TB, Lanzhou, Peoples R China

[19] Capital Med Univ, Beijing Chest Hosp, Beijing TB & Thorac Tumor Res Inst, Dept Bacteriol & Immunol,Beijing Key Lab Drug Resi, Beijing, Peoples R China

来源：

BMC MEDICINE | 2024年 / 22卷 / 01期

关键词：

Efficacy; Multidrug-resistant; RCT trial; Safety; Tuberculosis;

D O I：

10.1186/s12916-024-03694-4

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundWe 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.MethodsThis 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.ResultsBetween 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).ConclusionsThe 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.

引用

页数：2