Asthma and Airway Centre, University Health Network, Toronto Western Hospital, Rm 7-451 East Wing, 399 Bathurst Street, Toronto, ON, Canada.
BMC Pulm Med. 2014 Jan 17;14:4. doi: 10.1186/1471-2466-14-4.
Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) - tiotropium and glycopyrronium. Previous studies have compared glycopyrronium with open-label tiotropium. In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.
In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily. The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: -50 mL). Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George's Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.
657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study. Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: -32, 31 mL). Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0-4 h post-dose versus tiotropium (all p < 0.001). FEV1 area under the curve from 0-4 h (AUC0-4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12. Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant). Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035). Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).
In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.
目前有两种每日一次的长效抗毒蕈碱药物（LAMA）可用于治疗慢性阻塞性肺疾病（COPD） - 噻托溴铵和格隆溴铵。以前的研究比较了格隆溴铵与开放标签的噻托溴铵。在 GLOW5 研究中，我们比较了格隆溴铵与盲法噻托溴铵。
在这项双盲、双模拟、平行组、12 周研究中，中重度 COPD 患者按 1:1 随机分配接受格隆溴铵 50μg 每日一次或噻托溴铵 18μg 每日一次。主要目的是证明格隆溴铵与盲法噻托溴铵在治疗 12 周后（非劣效性边界：-50mL）的谷值用力呼气量 1 秒（FEV1）方面具有非劣效性。次要目的是评估格隆溴铵与噻托溴铵在其他肺量计结果、呼吸困难（过渡呼吸困难指数；TDI）、健康状况（圣乔治呼吸问卷；SGRQ）、每日急救药物使用、COPD 加重和 COPD 症状方面的差异。
657 名患者被随机分配（格隆溴铵：327；噻托溴铵：330）；96%（630 名）患者完成了研究。格隆溴铵和噻托溴铵在第 12 周的谷值 FEV1 均为 1.405L，符合非劣效性标准（平均治疗差异：0mL，95%CI：-32，31mL）。格隆溴铵在第 1 天首次给药后表现出快速支气管扩张作用，与噻托溴铵相比，在 0-4 小时的所有时间点上，FEV1 均显著更高（所有 p<0.001）。格隆溴铵在 0-4 小时（AUC0-4h）的 FEV1 曲线下面积（AUC0-4h）在第 1 天显著优于噻托溴铵（p<0.001），与第 12 周的噻托溴铵相当。格隆溴铵在 TDI 焦点评分、SGRQ 总分、急救药物使用和 COPD 加重率方面与噻托溴铵具有可比性（所有 p=无统计学意义）。与噻托溴铵相比，接受格隆溴铵治疗的患者在 12 周后总 COPD 症状评分也显著降低（p=0.035）。接受格隆溴铵和噻托溴铵治疗的患者报告不良反应的比例相似（40.4%和 40.6%）。
在中重度 COPD 患者中，每日一次的格隆溴铵 50μg 或噻托溴铵 18μg 治疗 12 周，提供了相似的疗效和安全性，格隆溴铵在第 1 天的作用开始时间比噻托溴铵更快。
