含贝达喹啉方案治疗耐多药肺结核对患者心电图QT间期的影响  

Effect of bedaquiline-containing regimen on QT interval in patients with multidrug-resistant tuberculosis

作　　者：谢莉[1] 高静韬[2] 马丽萍[1] 张立群[1] 孔忠顺[1] 吴晓光[1] 刘荣梅[1] 陈红梅[1] 宋艳华[1] 李雪莲[1] 黄麦玲[1] 李强[1] 吕子征 刘宇红[2] 高孟秋[1] XIE Li;GAO Jing-tao;MA Li-ping;ZHANG Li-qun;KONG Zhong-shun;WU Xiao-guang;LIU Rong-mei;CHEN Hong-mei;SONG Yan-hua;LI Xue-lian;HUANG Mai-ling;LI Qiang;LYU Zi-zheng;LIU Yu-hong;GAO Meng-qiu(Department of Tuberculosis,Beijing Chest Hospital,Capital Medical University,Beijing 101149,China)

机构地区：[1]首都医科大学附属北京胸科医院结核二科,101149 [2]首都医科大学附属北京胸科医院临床中心办公室,101149

出　　处：《中国防痨杂志》2020年第7期687-694,共8页Chinese Journal of Antituberculosis

基　　金：北京市科技计划课题(Z191100006619077);首都卫生发展科研专项(首发2020-2-2162);“十三五”国家科技重大专项(2018ZX10722301-001)。

摘　　要：目的探索含贝达喹啉方案对耐多药肺结核患者心电图QT间期(简称"QT")的影响,为贝达喹啉临床安全使用与监测提供依据。方法北京胸科医院在2018年2月至2019年10月依据纳入和排除标准入选符合条件的患者120例,给予含贝达喹啉的耐药结核病治疗方案,监测并记录患者治疗前基线及治疗后的第2、4、8、12、16、20、24周末及完成贝达喹啉用药疗程后12个月每12周检测1次心电图。按心率校正、采用Fridericia公式计算的QT值(QTcF值)。首先采用t检验、ANOVA检验及秩和检验分析患者基线QTcF值在不同年龄、性别、体质量指数和耐药类型组间的差异性;其次,采用独立样本t检验比较治疗期间不同时点QTcF值与其基线的差异;最后采用多因素logistic回归分析QT延长的影响因素。结果120例患者基线QTcF平均值为(404.90±19.27)ms,使用含贝达喹啉方案治疗过程中23例(19.2%)患者出现QTcF值较基线延长≥60 ms,10例(8.3%)患者同时出现QTcF≥500 ms。患者QTcF平均值随着贝达喹啉使用疗程时间增加逐渐增大,至20周末达峰值,且此前各时点QTcF值均与基线差异具有统计学意义:治疗2周末,QTcF值为(413.51±22.69)ms(t=4.064,P=0.000);治疗4周末,QTcF值为(413.38±17.81)ms(t=4.022,P=0.000);治疗8周末,QTcF值为(414.78±23.71)ms(t=3.796,P=0.000);治疗12周末,QTcF值为(416.23±25.06)ms(t=3.752,P=0.000);治疗16周末,QTcF值为(419.23±29.18)ms(t=4.584,P=0.000);治疗20周末,QTcF值为(425.45±30.84)ms(t=5.865,P=0.000)。完成贝达喹啉疗程后的6个月期间,QTcF平均值在第36周末、48周末分别为(419.10±31.38)ms和(419.60±27.74)ms,与基线比较差异均有统计学意义(治疗36周末,t=3.698,P=0.000;治疗48周末,t=2.790,P=0.007)。QTcF平均值在完成贝达喹啉疗程后的6-12个月期间与基线比较差异无统计学意义[治疗60周末,QTcF值为(409.70±19.60)ms(t=0.759,P=0.453);治疗72周末,QTcF值为(412.77±15.96)ms(t=2.051,P=0.051)]。在上述Objective To explore the effect of bedaquiline-containing regimen on QT interval in patients with multidrug-resistant tuberculosis(MDR-TB),with the purpose to provide evidence for clinical safe use and monitoring of the drug.Methods One hundred and twenty eligible patients were enrolled from Feb.2018 to Oct.2019 according to the inclusion and exclusion criteria in Beijing Chest Hospital,provided with bedaqulinecontaining treatment regimen.The QTcF values of electrocardiograph(ECG)were monitored and recorded at baseline before treatment and then serial follow-up ECG were done at the end of week 2,4,8,12,16,20,24 after treatment initiation.Thereafter once per 12 week for 1 year after bedaquiline duration was completed.Firstly,t-test,ANOVA test and Mann-Whitney U test were applied to analyze the distribution of baseline QTcF values among groups with age,gender,body mass index and drug resistance type.Secondly,independent sample t-test was used to compare the QTcF values at different time points during the treatment with that at baseline.Finally,multi-variate logistic regression analysis was performed to analyze the risk factors associated with QT interval prolongation.Results The mean value of QTcF of 120 patients at baseline was(404.90±19.27)ms.During exposure of bedaquiline-containing regimen,QTcF prolongation from baseline value≥60 ms occurred in 23 cases(19.2%)while QTcF≥500 ms occurred in 10 patients(8.3%).The mean value of QTcF increased gradually with the increase of bedaquiline administration duration and hit the peak at the end of week 20,and the QTcF monitored at each time point before it presented significant difference compared with that at baseline:at the end of week 2,QTcF was(413.51±22.69)ms(t=4.064,P=0.000);at the end of week 4,QTcF was(413.38±17.81)ms(t=4.022,P=0.000);at the end of week 8,QTcF was(414.78±23.71)ms(t=3.796,P=0.000);at the end of week 12,QTcF was(416.23±25.06)ms(t=3.752,P=0.000);at the end of week 16,QTcF was(419.23±29.18)ms(t=4.584,P=0.000);at the end of week 20,QTcF was(425

关 键 词：结核 肺 结核 抗多种药物性 药物疗法 心电描记术 药物毒性 贝达喹啉 

分 类 号：R521[医药卫生—内科学] R540.41[医药卫生—临床医学]