BACKGROUND:Indacaterol is the first once-daily, long-acting, inhaled β(2)-agonist bronchodilator for maintenance treatment of chronic obstructive pulmonary disease (COPD). Two studies (previously reported in a Congress abstract) were performed in 2010 to provide efficacy and tolerability data to support the application for approval in the United States of indacaterol 75 μg once daily, a dose lower than that previously investigated in most studies. OBJECTIVE:The primary objective was to evaluate the efficacy of indacaterol 75 μg once daily in terms of 24-hour post-dose ("trough") forced expiratory volume in the first second of respiration (FEV(1)) compared with placebo after 12 weeks of treatment. METHODS:Patients with moderate to severe COPD were randomized to receive double-blind treatment with indacaterol 75 μg once daily (n = 163 and 159) or placebo (n = 160 and 159) for 12 weeks. In addition to trough FEV(1) after 12 weeks, rescue albuterol use, health status (St. George's Respiratory Questionnaire [SGRQ]), and tolerability were evaluated. Clinically relevant differences between active and placebo treatments were defined as ≥120 mL for trough FEV(1) and a decrease of ≥4 units in SGRQ total score. RESULTS:Of patients enrolled in the 2 studies, 54% were men, and 90% and 94% were white, with mean age 64 and 61 years. Mean duration of COPD was 7 years; smoking history was 52 pack-years; and 45% and 37% of patients were receiving inhaled corticosteroid therapy. At week 12, indacaterol demonstrated clinically relevant bronchodilator efficacy, increasing trough FEV(1) by ≥120 mL versus placebo (P < 0.001), with significant bronchodilation maintained at all time points from 5 minutes to 24 hours post-dose. Over 12 weeks, relative to placebo, in patients receiving indacaterol therapy, rescue albuterol use was reduced by 1.2 and 0.7 puffs per day (P < 0.01), and the percentage of rescue-free days was increased by 13.7 and 8.4 (P < 0.01). At week 12, the SGRQ total score differed in the indacaterol group versus the placebo group by -3.8 and -3.6, respectively (P ≤ 0.01). Adverse events were reported for 49% and 45% of patients receiving indacaterol therapy, and for 46% and 41% receiving placebo. CONCLUSIONS:Compared with placebo, indacaterol 75 μg once daily provided statistically significant and clinically relevant 24-hour bronchodilation and was well tolerated. In patients receiving indacaterol, the reduction in rescue albuterol use was statistically significant. Changes in health status also were statistically significant compared with placebo, although the differences of 3.6 and 3.8 units were below the predefined 4-unit level of clinical relevance. The results of these studies suggest that indacaterol 75 μg once daily is an effective maintenance treatment in patients with moderate to severe COPD. ClinicalTrials.gov identifiers: NCT01072448 and NCT01068600.

译文

背景:茚达特罗是第一种每天一次,长效吸入的β(2)-激动剂支气管扩张药,用于维持治疗慢性阻塞性肺疾病(COPD)。 2010年进行了两项研究(以前在国会摘要中进行了报道),以提供功效和耐受性数据,以支持每天一次一次在美国批准茚达特罗75μg的申请,该剂量低于此前在大多数研究中所研究的剂量。
目的:主要目的是评估在呼吸的第一秒(FEV(1))与安慰剂治疗后的第十二个24小时给药后(“谷”)强制呼气量相比,每天一次茚达特罗75μg的疗效。数周的治疗。
方法:将中度至重度COPD患者随机接受每日两次(分别为n = 163和159)或安慰剂(分别为n = 163和159)或安慰剂(n = 160和159)接受双盲治疗,持续12周。除了在12周后进入低谷FEV(1)之外,还评估了沙丁胺醇的抢救使用,健康状况(圣乔治呼吸问卷[SGRQ])和耐受性。主动治疗和安慰剂治疗之间的临床相关差异被定义为低谷FEV(1)≥120 mL,SGRQ总得分降低≥4个单位。
结果:参与这两项研究的患者中,男性为54%,白人为90%和94%,平均年龄为64岁和61岁。 COPD的平均持续时间为7年;吸烟史为52包年。分别有45%和37%的患者接受吸入糖皮质激素治疗。在第12周时,茚达特罗证明了与临床相关的支气管扩张药功效,与安慰剂相比,谷量FEV(1)增加了≥120mL(P <0.001),并且在给药后5分钟至24小时的所有时间点均保持了显着的支气管扩张作用。在12周内,相对于安慰剂,接受茚达特罗治疗的患者每天使用沙丁胺醇的量减少了1.2和0.7帕夫斯(P <0.01),而无营救天数的百分比增加了13.7和8.4(P <0.01) )。在第12周时,茚达特罗组与安慰剂组的SGRQ总得分分别相差-3.8和-3.6(P≤0.01)。据报道,使用茚达特罗治疗的患者中有49%和45%的患者发生不良事件,接受安慰剂的患者中有46%和41%的患者发生了不良事件。
结论:与安慰剂相比,茚达特罗75μg每天一次可提供具有统计学意义和临床相关性的24小时支气管扩张,且耐受性良好。在接受茚达特罗的患者中,沙丁胺醇的抢救使用减少在统计学上是显着的。与安慰剂相比,健康状况的变化在统计学上也具有统计学意义,尽管3.6和3.8单位的差异低于临床相关性的预定4单位水平。这些研究的结果表明,对于中度至重度COPD患者,每天一次75 mg茚达特罗是一种有效的维持治疗方法。 ClinicalTrials.gov标识符:NCT01072448和NCT01068600。

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