格隆溴铵每日一次与沙美特罗/氟替卡松联合使用时，可显著改善慢性阻塞性肺疾病（COPD）患者的肺功能和健康状况：GLISTEN研究，一项随机对照试验。
Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study, a randomised controlled trial.
作者信息
Frith Peter A, Thompson Philip J, Ratnavadivel Rajeev, Chang Catherina L, Bremner Peter, Day Peter, Frenzel Christina, Kurstjens Nicol
机构信息
Respiratory Clinical Research Unit, Repatriation General Hospital, Adelaide, South Australia, Australia.
The Lung Health Clinic, Centre for Asthma Allergy and Respiratory Research, University of Western Australia, and the Lung Institute of Western Australia, Perth, Western Australia, Australia.
出版信息
Thorax. 2015 Jun;70(6):519-27. doi: 10.1136/thoraxjnl-2014-206670. Epub 2015 Apr 3.
BACKGROUND
The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).
METHODS
This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.
RESULTS
773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) -7 mL (SE 17.4) with a lower limit for non-inferiority of -60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff -2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff -0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.
CONCLUSIONS
GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.
TRIAL REGISTRATION NUMBER
NCT01513460.
背景
对于中度/重度慢性阻塞性肺疾病（COPD），各种治疗组合的最佳使用方法尚不清楚。GLISTEN试验比较了两种长效抗毒蕈碱拮抗剂（LAMA）与吸入性糖皮质激素（ICS）和长效β2受体激动剂（LABA）联合使用时的疗效。
方法
这项针对中度/重度COPD患者的随机、双盲、安慰剂对照试验，比较了每日一次的50μg格隆溴铵（GLY）、每日一次的18μg噻托溴铵（TIO）或安慰剂（PLA）与每日两次的50/500μg沙美特罗/丙酸氟替卡松（SAL/FP）联合使用的情况。主要目的是确定12周后GLY+SAL/FP与TIO+SAL/FP在谷值FEV1上的非劣效性。一个重要的次要目的是，在SAL/FP中添加GLY是否比单独使用SAL/FP更好。
结果
773例患者（预测平均FEV1为57.2%）被随机分组；84.9%完成了试验。在第12周时，GLY+SAL/FP在谷值FEV1方面显示出与TIO+SAL/FP非劣效：最小二乘均数治疗差异（LSMdiff）为-7mL（标准误17.4），非劣效下限为-60mL。与PLA+SAL/FP相比，GLY+SAL/FP在第12周时谷值FEV1有显著增加（LSMdiff为101mL，p<0.001）。在12周时，与PLA+SAL/FP相比，GLY+SAL/FP在圣乔治呼吸问卷总分方面有显著改善（LSMdiff为-2.154，p=0.02）。与PLA+SAL/FP相比，GLY+SAL/FP在急救药物使用方面有显著减少（LSMdiff为-0.72吸/天，p<0.001）。GLY+SAL/FP、TIO+SAL/FP和PLA+SAL/FP的严重不良事件相似，发生率分别为5.8%、8.5%和5.8%。
结论
GLY+SAL/FP在肺功能、健康状况和急救药物使用方面显示出与TIO+SAL/FP相当的改善。重要的是，与SAL/FP相比，在SAL/FP中添加GLY在肺功能、健康状况和急救药物使用方面有显著改善。
试验注册号
NCT01513460。
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