研究人员进行了一项3期试验,评价了用加替沙星替代乙胺丁醇的4个月方案对治疗利福平敏感的肺结核病人的有效性和安全性。结果发现该方案与6个月标准治疗方案相比,在治疗失败、复发、在治疗期间死亡或退出等方面,没有显示出非劣效性。

20141023日《新英格兰医学杂志》

中文翻译


 

【题目】包含加替沙星的4个月方案治疗肺结核

【译文】

背景:缩短肺结核治疗的疗程是对病人管理和疾病控制的巨大进步。本3期试验评价了包含加替沙星的4个月方案对治疗利福平敏感的肺结核病人的有效性和安全性。

方法:我们开展了一项非劣效性、随机、开放标签的对照试验,包括来自撒哈拉沙漠以南的5个非洲国家的新诊断肺结核的病人,年龄在18-65岁的,痰涂片阳性,对利福平敏感。标准的6个月治疗方案包括在2个月的强化期使用乙胺丁醇,而4个月方案是在强化期用加替沙星(400mg/天)代替乙胺丁醇,并在之后与利福平和异烟肼一起在维持期使用。主要的有效性终点是在治疗结束24个月后测量不良结局(治疗失败、复发、在治疗期间死亡或退出),非劣效性边界为6个百分点,校正国家因素。

结果:总共1836个病人被分配到4个月方案组(试验组)和标准方案组(对照组)。两组之间病人的基本特征匹配良好。在结束治疗24个月后,不良结局风险的校正差异(试验组[21.0%]减对照组[17.2%])在修饰意向治疗人群中为3.5个百分点(95CI-0.77.7)。国家之间存在异质性(相互作用P=0.02,不良结局率存在差异,范围从塞内加尔的-5.4%到几内亚12.3%),基本资料中的空洞状态(相互作用P=0.04)和身体质量指数(相互作用P=0.10)也存在异质性。与4个月方案相比,标准方案与治疗期间病人更高的脱落率有关(5.0% vs 2.7%),治疗失败率更高(2.4% vs 1.7%),但是复发更少(7.1% vs 14.6%)。没有证据表明4个月方案有更多的危险导致QT间期延长或血糖异常。

结论:4个月方案与标准方案相比,在主要疗效终点方面没有显示出非劣效性。

 

英文原稿


 

[Title] A four-month gatifloxacin-containing regimen for treating tuberculosis.
[Authors] Merle CS, Fielding K, Sow OB, Gninafon M, Lo MB, Mthiyane T, et al.
[Abstract]
BACKGROUND: Shortening the course of treatment for tuberculosis would be a major improvement for
case management and disease control. This phase 3 trial assessed the efficacy and safety of a 4-month
gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis.

METHODS: We conducted a noninferiority, randomized, open-label, controlled trial involving patients 18
to 65 years of age with smear-positive, rifampin-sensitive, newly diagnosed pulmonary tuberculosis in five
sub-Saharan African countries. A standard 6-month regimen that included ethambutol during the 2-month
intensive phase was compared with a 4-month regimen in which gatifloxacin (400 mg per day) was
substituted for ethambutol during the intensive phase and was continued, along with rifampin and
isoniazid, during the continuation phase. The primary efficacy end point was an unfavorable outcome
(treatment failure, recurrence, or death or study dropout during treatment) measured 24 months after the
end of treatment, with a noninferiority margin of 6 percentage points, adjusted for country.
RESULTS: A total of 1836 patients were assigned to the 4-month regimen (experimental group) or the
standard regimen (control group). Baseline characteristics were well balanced between the groups. At 24
months after the end of treatment, the adjusted difference in the risk of an unfavorable outcome
(experimental group [21.0%] minus control group [17.2%]) in the modified intention-to-treat population
(1356 patients) was 3.5 percentage points (95% confidence interval, -0.7 to 7.7). There was heterogeneity
across countries (P=0.02 for interaction, with differences in the rate of an unfavorable outcome ranging
from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal) and in baseline cavitary
status (P=0.04 for interaction) and body-mass index (P=0.10 for interaction). The standard regimen, as
compared with the 4-month regimen, was associated with a higher dropout rate during treatment
(5.0% vs. 2.7%) and more treatment failures (2.4% vs. 1.7%) but fewer recurrences (7.1% vs.
14.6%). There was no evidence of increased risks of prolongation of the QT interval or dysglycemia
with the 4-month regimen.
CONCLUSIONS: Noninferiority of the 4-month regimen to the standard regimen with respect to the
primary efficacy end point was not shown.

 

 

原文网址:

http://www.nejm.org/doi/full/10.1056/NEJMoa1315817

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