关键词: 结核,肺, 结核,抗多种药物性, 炙甘草汤颗粒剂, 贝达喹啉, 药物评价, 观察性研究

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