英国研究人员开展了一项随机、双盲、安慰剂对照的3期临床试验,在非洲病人中,观察与传统的抗痨方案相比,两种用莫西沙星替代异烟肼或乙胺丁醇的4个月方案的效果。结果显示,两组包含莫西沙星的方案对细菌负荷在初始有更快的下降,但未显示出非劣效于标准6个月治疗方案。

20141023日《新英格兰医学杂志》

中文翻译


 

【题目】基于莫西沙星的4个月方案治疗药物敏感的肺结核

【译文】

背景:早期和临床前期的研究提示包含莫西沙星的方案可以在4个月有效治疗无并发症的痰涂片阳性的肺结核病人。

方法:我们开展了一项随机、双盲、安慰剂对照的3期临床试验,检测与对照方案相比,两种包含莫西沙星的方案的非劣效性。1组病人接受异烟肼+利福平+吡嗪酰胺+乙胺丁醇治疗8周,之后使用异烟肼+利福平18周(对照组)。在第2组,我们用莫西沙星替代乙胺丁醇治疗17周,之后安慰剂治疗9周(异烟肼组)。在第3组,我们用莫西沙星替代异烟肼治疗17周,之后安慰剂治疗9周(乙胺丁醇组)。主要终点是随机分组后18个月内治疗失败或复发。

结果:在参与随机分配的1931个病人中,按方案分析,获得良好结局的病人在异烟肼组(85%)和乙胺丁醇组(80%)均较对照组(92%)少,对照组与异烟肼组相比优势差异为6.195%CI1.710.5),与乙胺丁醇组相比为11.495%CI6.716.1)。进行修饰意向治疗分析和全部敏感性分析后结果均一致。与对照组相比,固体和液体基质痰培养转为阴性的时间的危险比在异烟肼组合乙胺丁醇组的范围是1.171.25,提示时间更短,所有病人中95%可信区间的低限均超过1.00。各组34级不良事件的发生率没有明显差别,异烟肼组有127个病人(19%)报告不良事件,乙胺丁醇组111人(17%),对照组123人(19%)。

结论:与对照组相比,两组包含莫西沙星的方案对细菌负荷在初始有更快的下降。但是,这两个方案没有显示出非劣效性,提示4个月的短期治疗在此情况下无效。

 

 英文原稿


 

[Title] Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis.

[Authors] Gillespie SH, Crook AM, McHugh TD, Mendel CM, Meredith SK, Murray SR, et al.

[Abstract]

BACKGROUND: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could
allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis.

METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the
noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group
of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks
of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin
for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced
isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The
primary end point was treatment failure or relapse within 18 months after randomization.

RESULTS: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable
outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%)
than in the control group (92%), for a difference favoring the control group of 6.1 percentage points
(97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points
(97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-
to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both
solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group,
ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence
intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or
4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the
ethambutol group, and 123 (19%) in the control group.

CONCLUSIONS: The two moxifloxacin-containing regimens produced a more rapid initial decline in
bacterial load, as compared with the control group. However, noninferiority for these regimens was
not shown, which indicates that shortening treatment to 4 months was not effective in this setting.

 

原文网址:

http://www.nejm.org/doi/full/10.1056/NEJMoa1407426

 

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