首次复治敏感肺结核治疗新方案疗效的验证性研究

Effect of a new treatment regimen on patients with initially retreated drug-sensitive pulmonary tuberculosis

目的:分析复治肺结核治疗新方案(简称“新方案”)与复治标准方案(简称“标准化方案”)治疗首次复治敏感肺结核的有效性及安全性。方法:采用多中心前瞻性队列研究方法,选取2019年1月至2021年12月期间在中国14个省及3个直辖市中的24家结核病定点医疗机构住院确诊的592例首次复治肺结核患者(包括敏感、单耐药、多耐药及部分菌阴复治肺结核),将患者随机纳入新方案组[4H-L_(2)-E-Z-Lfx/4H-L_(2)-E;H:异烟肼(体质量<50 kg,0.3 g/d;体质量≥50 kg,0.4~0.5 g/d),L:利福喷丁(0.6 g/次,2次/周),E:乙胺丁醇(体质量<50 kg,0.75 g/d;体质量≥50 kg,0.75~1.0 g/d),Z:吡嗪酰胺(1.5 g/d),Lfx:左氧氟沙星(0.5~0.6 g/d)]和标准化方案组(3H-R-E-Z/6H-R-E,常规剂量;R:利福平)。本研究参照纳排标准选取其中首次复治敏感肺结核患者(均为涂阳培阳)为研究对象,比较新方案组患者和标准化方案组的治疗成功率、失败率、不良反应发生率等,以评估新方案在复治敏感肺结核患者中的有效性及安全性。结果:共纳入首次复治敏感肺结核患者238例,其中新方案组172例(72.3%),标准化方案组66例(27.7%)。新方案组治疗成功率[77.3%(133/172)]高于标准化方案组[62.1%(41/66)],治疗失败率[4.7%(8/172)]低于标准化方案组[27.3%(18/66)],差异均有统计学意义(χ^(2)=5.609,P=0.018;χ^(2)=25.083,P=0.000),但两组患者不良反应发生率[4.7%(8/172)和3.0%(2/66)]差异无统计学意义(Fisher精确概率法,P=0.731)。结论:新方案可提高首次复治敏感肺结核的治疗成功率及降低治疗失败率,总体治疗效果及安全性均较好。

Objective:To evaluate the efficacy and safety of a new treatment regimen against a standardized regimen on patients with retreated drug-susceptible pulmonary tuberculosis(PTB).Methods:This multi-centered study adopted a prospective study design,592 patients with initially retreated PTB(including drug-susceptible,mono-drug resistance,poly-drug resistance and a few cases of smear negative retreated PTB)whom had been randomized into the new regimen arm(4H-L_(2)-E-Z-Lfx/4H-L_(2)-E;H:isoniazid,L:rifapentine,E:ethambutol,Z:pyrazinamide,Lfx:levofloxacin;body mass<50 kg,H for 0.3 g/d,E for 0.75 g/d;body mass≥50 kg,H for 0.4-0.5 g/d,E for 0.75-1.0 g/d;regardless of body weight,L was 0.6 g,twice a week;Z:1.5 g/d,Lfx:0.5-0.6 g/d),and the standardized regimen arm(3H-R-E-Z/6H-R-E using conventional doses;R:rifampicin),diagnosed and hospitalized in between Jan 2019 and Dec 2021 by 24 PTB designated hospitals across 14 provinces and 3 municipalities in China were screened at baseline.According to inclusion and exclusion criteria,only those with initially retreated drug-susceptible PTB were recruited as study subjects.The rates of treatment success,treatment failure as well as incidence of adverse events were compared,safety and efficacy of the new regimen derived.Results:The final analysis included 238 cases,of which 172 cases(72.3%)were randomized into the new regimen arm,66 cases(27.7%)into the standardized regimen arm.The success rate of the new regimen arm was higher than that of the standardized regimen arm(77.3%(133/172)vs.62.1%(41/66);χ^(2)=5.609,P=0.018),and the failure rate was lower than that of the standard regimen arm(4.7%(8/172)vs.27.3%(18/66);χ^(2)=25.083,P=0.000).There was no significant difference in the incidence of adverse reactions between the two arms(4.7%(8/172)vs.3.0%(2/66);Fisher test,P=0.731).Conclusion:Compare to the standardized regimen,the new retreatment regimen had improved the treatment success rate and lowered the rate of treatment failure among patients with retreated drug-sensitive PTB,demonstrated good overall safety and efficacy profile.