Effect of Roast Radix Glycyrrhizae Decoction Granules on the prolongation of QT interval caused by bedaquiline in the treatment of multidrug-resistant pulmonary tuberculosis

doi:10.19982/j.issn.1000-6621.20210687

Abstract

Abstract:

Objective: To explore the effect of Roast Radix Glycyrrhizae Decoction Granules (RRGDG) on the prolongation of QT interval caused by the regimen containing bedaquiline in the treatment of multidrug-resistant pulmonary tuberculosis. Methods: From September 2018 to October 2020,45 patients with pulmonary tuberculosis who were treated with bedaquiline-containing regimen and met the inclusion criteria in Hangzhou Chest Hospital Affiliated to School of Medicine of Zhejiang University were selected as the research objects. They were randomly allocated into Traditional Chinese Medicine (TCM) group (23 cases) and control group (22 cases) using random number table. Patients in the TCM group were treated with RRGDG during the first month of the bedaquiline-containing anti-tuberculosis therapy, while the control group did not take RRGDG. ECGs were performed and recorded before the treatment and at 2,4,8,12,16,20 and 24 weeks after the treatment started, and QTcF values were calculated (the corrected QT intervals were calculated according to Fridericia formula). Results: During 24 weeks of bedaquiline administration, the adverse events were as follows: QTcF>450 ms in 8 patients (8/23,34.8%) and QTcF prolongation >30 ms comparing with baseline (ΔQTcF) in 16 patients (16/23,69.6%) in TCM group; QTcF value >450 ms in 16 patients (16/22,72.7%) and ΔQTcF value ≥30 ms in 20 patients (20/22,90.9%) in the control group. The serious adverse events were as follows: QTcF value ≥500 ms in 1 case (1/23,4.3%), which occurred at the 8th week of treatment, and ΔQTcF ≥60 ms in 4 cases (4/23,17.4%) in the TCM group; QTcF value ≥500 ms in 4 cases (4/22,18.2%), occurred at 4th (1 case), 8th (1 case), and 24th (2 cases) week of treatment, respectively, and ΔQTcF ≥60 ms in 11 cases (11/22,50.0%) in the control group. There were significant differences between the TCM group and the control group in adverse event (QTcF>450 ms) incidence and serious adverse event (ΔQTcF ≥60 ms) incidence (χ² values were 6.505 and 5.380, P values were 0.011 and 0.020, respectively). Conclusion: The regimen containing bedaquiline in the treatment of multidrug-resistant tuberculosis could induce prolongation of QT intervals of patients. Combined use of RRGDG could reduce the incidence of QTcF>450 ms and ΔQTcF≥60 ms.

Key words: Tuberculosis,pulmonary, Tuberculosis,multidrug resistance, Roast Radix Glycyrrhizae Decoction Granules, Bedaquiline, Drug evaluation, Observational study

CLC Number:

R521
R286

QI Qi, CAI Qing-shan, CUI Yan-fei, CHEN Yuan-yuan, BAO Zhi-jian, QIU Mei-hua, GUO Yi-nan, MA Xiao-qing. Effect of Roast Radix Glycyrrhizae Decoction Granules on the prolongation of QT interval caused by bedaquiline in the treatment of multidrug-resistant pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2022, 44(3): 246-251. doi: 10.19982/j.issn.1000-6621.20210687

Figures/Tables 4

References 24

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基线特征	中药组(23例)	对照组(22例)	统计学检验值	P值
年龄[岁, M(Q₁,Q₃)]	28(23,40)	32(29,48)	Z=-1.627	0.104
QTcF值(ms,$\bar{x} \pm s$)	406.43±18.25	402.77±21.96	t=0.610	0.545
性别[例,构成比(%)]			χ²=0.178	0.673
男性	16(69.6)	14(63.6)
女性	7(30.4)	8(36.4)
耐药类型[例,构成比(%)]			χ²=0.545	0.909
RR-TB	2(8.7)	1(4.5)
MDR-TB	5(21.7)	6(27.3)
pre-XDR-TB	12(52.2)	12(54.6)
XDR-TB	4(17.4)	3(13.6)
药物组合[例,构成比(%)]			χ²=1.299	0.729
Bdq+Lfx	3(13.0)	1(4.6)
Bdq+Cfz	11(47.8)	12(54.5)
Bdq+Lfx+Cfz	6(26.2)	7(31.8)
Bdq	3(13.0)	2(9.1)

不良事件	中药组(23例)	对照组(22例)	χ²值	P值
QTcF>450ms	8(34.8)	16(72.7)	6.505	0.011
ΔQTcF≥30ms	16(69.6)	20(90.9)	2.007	0.157
QTcF≥500ms	1(4.3)	4(18.2)	1.003	0.317
ΔQTcF≥60ms	4(17.4)	11(50.0)	5.380	0.020

治疗时间	ΔQTcF值[ms,M(Q₁,Q₃)]		差值中位数 (95%CI)	Z值	P值
治疗时间	中药组(23例)	对照组(22例)	差值中位数 (95%CI)	Z值	P值
第2周	18.0(-1.0,30.0)	33.0(11.8,44.5)	-14.0(-28.0,-2.0)	-2.238	0.025
第4周	24.0(7.0,43.0)	35.5(7.3,49.0)	-6.0(-15.0,10.0)	-0.784	0.433
第8周	14.0(-6.0,49.0)	19.0(3.3,60.3)	-11.0(-31.0,9.0)	-1.113	0.266
第12周	18.0(-11.0,31.0)	24.5(-4.5,55.8)	-15.0(-34.0,5.0)	-1.488	0.137
第16周	21.0(-6.0,40.0)	30.0(9.0,54.8)	-13.0(-31.0,3.0)	-1.499	0.134
第20周	14.0(-8.0,34.0)	35.0(10.8,45.0)	-14.0(-29.0,2.0)	-1.658	0.097
第24周	21.0(-4.0,41.0)	26.5(4.5,53.0)	-11.0(-36.0,10.0)	-0.897	0.370

患者编号	组别	性别	年龄 (岁)	BMI	严重不良事件类型	发生时间 (周)	耐药类型	药物组合
例1	中药组	女	26	17.3	QTcF≥500ms ΔQTcF≥60ms	8	XDR-TB	Bdq+Cfz
例2	中药组	男	20	23.1	ΔQTcF≥60ms	16	XDR-TB	Bdq+Cfz
例3	中药组	女	34	19.1	ΔQTcF≥60ms	24	MDR-TB	Bdq+Cfz+Lfx
例4	中药组	男	20	23.4	ΔQTcF≥60ms	20	MDR-TB	Bdq+Cfz+Lfx
例5	对照组	女	50	19.2	QTcF≥500ms ΔQTcF≥60ms	24	pre-XDR-TB	Bdq+Cfz
例6	对照组	男	49	22.0	QTcF≥500ms ΔQTcF≥60ms	24	MDR-TB	Bdq+Cfz+Lfx
例7	对照组	女	34	21.1	QTcF≥500ms ΔQTcF≥60ms	4	MDR-TB	Bdq+Cfz+Lfx
例8	对照组	男	49	17.3	QTcF≥500ms ΔQTcF≥60ms	8	pre-XDR-TB	Bdq+Cfz
例9	对照组	男	42	28.4	ΔQTcF≥60ms	24	XDR-TB	Bdq+Cfz
例10	对照组	女	31	19.5	ΔQTcF≥60ms	12	MDR-TB	Bdq+Cfz
例11	对照组	女	32	20.6	ΔQTcF≥60ms	2	XDR-TB	Bdq+Cfz
例12	对照组	男	24	19.9	ΔQTcF≥60ms	4	XDR-TB	Bdq+Cfz
例13	对照组	女	29	18.8	ΔQTcF≥60ms	12	MDR-TB	Bdq+Cfz+Lfx
例14	对照组	男	29	21.4	ΔQTcF≥60ms	8	pre-XDR-TB	Bdq+Cfz
例15	对照组	女	23	19.9	ΔQTcF≥60ms	2	pre-XDR-TB	Bdq+Cfz