Section of Pulmonary and Critical Care Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
Division of Respiratory Medicine, University Hospital, Katholieke Universiteit, Leuven, Belgium.
Eur Respir J. 2014 Jun;43(6):1599-609. doi: 10.1183/09031936.00124013. Epub 2013 Oct 31.
We evaluated the effect of QVA149, a dual bronchodilator combining indacaterol and glycopyrronium, on direct patient-reported dyspnoea in patients with moderate-to-severe chronic obstructive pulmonary disease. In this multicentre, blinded, double-dummy, three-period crossover study, 247 patients were randomised to once-daily QVA149 110/50 μg, placebo or tiotropium 18 μg. Superiority of QVA149 versus placebo (primary objective) and tiotropium (secondary objective) was assessed for improvement in dyspnoea via the self-administered computerised (SAC) version of the Baseline and Transition Dyspnoea Index after 6 weeks. Secondary end-points included lung function, rescue medication use and safety. After 6 weeks, the SAC Transition Dyspnoea Index total score was significantly higher with QVA149 versus placebo (least squares mean (LSM) treatment difference 1.37, p<0.001) and tiotropium (LSM treatment difference 0.49, p=0.021). QVA149 provided significant improvements in lung function, with higher forced expiratory volume in 1 s area under the curve from 0-4 h post-dose versus placebo and tiotropium at day 1 and week 6 (all p<0.001). Rescue medication use was significantly lower with QVA149 versus placebo (p<0.001) and tiotropium (p=0.002). All treatments were well tolerated. Once-daily QVA149 provided superior improvements in patient-reported dyspnoea and lung function versus placebo and tiotropium. These benefits were associated with improvements in other symptoms and reduced use of rescue medication.
我们评估了双支气管扩张剂茚达特罗/格隆溴铵(QVA149)对中重度慢性阻塞性肺疾病患者直接报告的呼吸困难的影响。在这项多中心、盲法、双盲、三周期交叉研究中,247 名患者随机接受每日一次 QVA149 110/50μg、安慰剂或噻托溴铵 18μg 治疗。通过 6 周后使用自我管理计算机化(SAC)版基础和过渡呼吸困难指数评估 QVA149 相对于安慰剂(主要终点)和噻托溴铵(次要终点)改善呼吸困难的优越性。次要终点包括肺功能、急救药物使用和安全性。6 周后,与安慰剂相比,QVA149 治疗的 SAC 过渡呼吸困难指数总分显著升高(最小二乘均数[LSMean]治疗差异 1.37,p<0.001)和噻托溴铵(LSMean 治疗差异 0.49,p=0.021)。QVA149 可显著改善肺功能,与安慰剂和噻托溴铵相比,第 1 天和第 6 周 0-4 小时后 1 秒用力呼气量曲线下面积更高(均 p<0.001)。与安慰剂相比,QVA149 组急救药物使用率显著降低(p<0.001)和噻托溴铵(p=0.002)。所有治疗均耐受良好。每日一次 QVA149 与安慰剂和噻托溴铵相比,可显著改善患者报告的呼吸困难和肺功能。这些益处与其他症状的改善和急救药物使用的减少相关。