Department of Respiratory Diseases, Atrium Medisch Centrum, Heerlen, The Netherlands.
Thorax. 2010 Dec;65(12):1086-91. doi: 10.1136/thx.2010.139113. Epub 2010 Oct 26.
This randomised, double-blind, placebo controlled, four-period crossover study assessed the efficacy and safety of once-daily QVA149, a dual bronchodilator consisting of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237), in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
Patients (N=154) were randomly assigned to receive QVA149 (indacaterol/NVA237) 300/50 μg, indacaterol 300 μg, indacaterol 600 μg, or placebo, once daily for 7 days with a 7-day washout period between each treatment. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) (mean of 23 h 15 min and 23 h 45 min post-dose values) on day 7. Other endpoints included trough FEV1 on day 1, individual time point FEV1 and monitoring and recording of all adverse events.
A total of 135 (87.7%) patients completed the study (all randomly assigned patients: mean age 61.7 years, 61.4% male, post-bronchodilator FEV1 52.2% predicted, FEV1/forced vital capacity 47.6%). The estimated treatment difference (95% CI) for trough FEV1 on day 7 between QVA149 and placebo was 226 ml (192 to 260; p<0.001). The estimated treatment difference between QVA149 and indacaterol 300 and 600 μg was 123 ml (89 to 157; p<0.001) and 117 ml (83 to 150; p<0.001), respectively. The improvements in mean trough FEV1 exceeded the predefined minimal clinically important differences of 100–140 ml for QVA149 versus placebo and indacaterol. Similar results were observed on day 1. All treatments were well tolerated.
QVA149 demonstrated rapid and sustained bronchodilation with significant improvements compared with indacaterol monotherapy and placebo in patients with COPD.
NCT00570778.
这项随机、双盲、安慰剂对照、四周期交叉研究评估了每日一次 QVA149（由长效β2-激动剂茚达特罗和长效毒蕈碱拮抗剂格隆溴铵组成的双重支气管扩张剂）在中重度慢性阻塞性肺疾病（COPD）患者中的疗效和安全性。
患者（N=154）随机分为接受 QVA149（茚达特罗/NVA237）300/50μg、茚达特罗 300μg、茚达特罗 600μg 或安慰剂，每天一次，共 7 天，每个治疗周期之间有 7 天洗脱期。主要终点是第 7 天的谷值用力呼气量 1 秒（FEV1）（给药后 23 小时 15 分钟和 23 小时 45 分钟的平均值）。其他终点包括第 1 天的谷值 FEV1、各个时间点的 FEV1 以及所有不良事件的监测和记录。
共有 135 名（87.7%）患者完成了研究（所有随机分配的患者：平均年龄 61.7 岁，61.4%为男性，支气管扩张剂后 FEV1 为预计值的 52.2%，FEV1/用力肺活量为 47.6%）。QVA149 与安慰剂相比，第 7 天谷值 FEV1 的估计治疗差异（95%CI）为 226ml（192 至 260；p<0.001）。QVA149 与茚达特罗 300μg 和 600μg 的估计治疗差异分别为 123ml（89 至 157；p<0.001）和 117ml（83 至 150；p<0.001）。QVA149 与安慰剂和茚达特罗相比，平均谷值 FEV1 的改善均超过了 100-140ml 的预设最小临床重要差异。在第 1 天也观察到了类似的结果。所有治疗均耐受良好。
与茚达特罗单药治疗和安慰剂相比，QVA149 可快速且持续地扩张支气管，在 COPD 患者中可显著改善。
NCT00570778。
