首次复治肺结核患者短程化疗新方案的临床研究

A clinical study of short course chemotherapy for first retreatment pulmonary tuberculosis patients

目的观察首次复治肺结核患者采用短程化疗方案的疗效和安全性。方法于2009年7月至2012年6月，采用多中心、随机、对照、开放、前瞻性队列研究方法，对全国17家结核病防治机构的首次复治涂阳肺结核患者共542例进行治疗研究。患者被数字表法随机分为4个组，分别为标准复治方案组（A组，123例；2S-H—RE-Z／6H-R-E）、氧氟沙星组（B组，142例；20frPa-R-E-Z／60fx-Pa-R）、左氧氟沙星组（C组：137例；2Lfx-Pa-R-E-Z／6Lfx-Pa-R）和超短程组（D组：140例；5Pa-Rfb-E-Z-Mfx）。各组患者结束治疗后随访2年，比较新方案的疗效、依从性、不良反应发生率和复发率。结果治疗后4个组的治疗成功率分别为68．3％（84／123）、72．5Z（103／142）、71．5％（98／137）和81．4％（114／140），其中D组的治疗成功率明显高于A组，差异有统计学意义（χ2=6．07，P=0．014）。各组患者的脱落率分别为20．3％（25／123）、14．8Z（21／142）、20．4％（28／137）和11．4％（16／140），其中D组的脱落率明显低于A组，差异有统计学意义（χ2=3．94，P=0．047）。共有289例患者报道了药物不良反应，发生率为52．oH（289／556）；其中，患者发生34级药物不良反应者A组有14例（11．4％）、B组有7例（4．9％）、C组有12例（8．8％）、D组有7例（5．0％）；4个组之间差异无统计学意义（χ2=5．67，P=0．129）。4个组患者的复发率如下：A组21．4％（12／56）、B组23．3％（17／73）、C组2．9％（2／70）和D组9．7％（7／72），差异有统计学意义（χ2=10．87，P=0．001）。结论5个月Pa—Rfb-E-Z—Mfx短程化疗方案治疗首次复治肺结核患者有较好的疗效和安全性，并可缩短疗程。

Objective To evaluate the efficacy and safety of short course chemotherapy to treat first retreatment pulmonary tuberculosis. Methods A multi-center, randomized, controlled and open prospective clinical trial was coducted in 17 tuberculosis dispensaries from July, 2009 to June 2012. A total of 542 first retreatment pulmonary tuberculosis patients with positive smear were assigned into 4 different groups： Group A （n= 123）： WHO stan- dardized regime; Group B （n=142） ： started with 2 months of pasiniazide （Pa）, ofloxacin （Ofx）, rifampin （R）, ethanbutol （E） and pyrazinamide （Z）, followed by 6 months of Ofx-Pa-R Group C （n= 137）, started with 2 months of Pa, levofloxacin （Lfx）, R, E, and pyrazinamide （Z）, followed by 6 months of Lfx-Pa-R; Group D （n=140）： 5 months of moxifloxacin （Mfx）, Pa, Rifabutin （Rfb）, E, Z. All the patients were followed up for 2 years after treatment. The outcome, compliance, adverse effects and relapse rate were observed. Results Therapeutic success rates of the four groups were 68.3% （84/123）, 72.5% （103/142）, 71.5% （98/137） and 81.4% （114/140）, respectively; the rate of Group D was significantly higher than that of Group A （χ2= 6.07, P = 0. 014）. The drop-off rates of four groups were 20.3% （25/123）, 14.8% （21/142）,20.4% （28/137） and 11.4% （16/140）, respectively; the rate of Group D was significantly lower than that of Group A （χ2=3.94, P=0. 047）. There were totally 289 cases who had adverse events with the incidence of 52.0% （289/556）. The incidence of grade 3--4 adverse effects were 11.4% in Group A （n=14）, 4. 9% in Group B （n=7） 8.8% in Group C （n=12） and 5.0% in Group D （n=7）, differences were not statistically significant （χ2 =5.67, P=0. 129）. The rdapse ratea of 4 groups were 21, 4%（12/56）, 23.3% （17/73）, 2.9% （2/70） and 9.7% （7/72）, respectively, differences were not statistically significant （χ2=10.87,P=0. 001）. Conclusion The novel regimen of Pa Rfb-E-Z-Mfx had better efficacy than standardized regimen and could shorten the treatment duration to 5 months.