Kerwin Edward, Siler Thomas M, Korenblat Phillip, White Alexander, Eckert Joerg H, Henley Michelle, Patalano Francesco, D'Andrea Peter
Clinical Research Institute of Southern Oregon, Medford.
Midwest Chest Consultants, St. Charles, Missouri.
Chronic Obstr Pulm Dis. 2016 Mar 28;3(2):549-559. doi: 10.15326/jcopdf.3.2.2015.0157.
Long-acting bronchodilators including muscarinic antagonists are central to the management of patients with COPD. The lycopyrrolate ffect on syptoms and lung function (GEM2) study assessed the efficacy and safety of twice-daily glycopyrrolate 15.6 μg in patients with moderate-to-severe airflow limitation. This 12-week multicenter, double-blind study randomized (1:1) patients to glycopyrrolate 15.6 μg twice daily (b.i.d.) or placebo both delivered via the Neohaler device. The primary objective was superiority of glycopyrrolate compared with placebo for forced expiratory volume in 1 second (FEV) standardized area under curve (AUC) between 0 and 12 hours post dosing (FEV AUC)at week 12. Other outcomes included additional spirometry parameters, health status using St George's Respiratory Questionnaire (SGRQ), dyspnea via Transition Dyspnea Index (TDI), rescue medication use and COPD symptoms reported by patients via the electronic diary. Safety was also assessed. Of the 432 patients randomized (glycopyrrolate, n=216; placebo, n=216), 96% completed the planned treatment phase. The study met its primary objective (superiority of glycopyrrolate compared with placebo for FEV AUC).Compared with placebo, glycopyrrolate showed significant improvements in lung function parameters (<0.001). Health status (SGRQ total score and COPD assessment test), rescue medication use and daily total COPD symptom scores were significantly improved with glycopyrrolate versus placebo over 12 weeks. Improvements in dyspnea were observed with glycopyrrolate and placebo although the treatment difference was not statistically significant. Overall, differences in the incidences of adverse events and serious adverse events between the groups were not considered clinically meaningful. No deaths were reported. Twice-daily glycopyrrolate 15.6 μg showed statistically significant and clinically meaningful improvements compared with placebo in lung function, COPD symptoms, health status, and rescue medication usage in COPD patients with moderate-to-severe airflow limitation.
NCT01715298.
包括毒蕈碱拮抗剂在内的长效支气管扩张剂是慢性阻塞性肺疾病（COPD）患者管理的核心。格隆溴铵对症状和肺功能的影响（GEM2）研究评估了每日两次吸入15.6μg格隆溴铵对中重度气流受限患者的疗效和安全性。这项为期12周的多中心、双盲研究将患者按1:1随机分为每日两次吸入15.6μg格隆溴铵组（bid）或安慰剂组，均通过Neohaler装置给药。主要目标是在第12周时，格隆溴铵组与安慰剂组相比，给药后0至12小时内1秒用力呼气容积（FEV）标准化曲线下面积（AUC）（FEV AUC）具有优越性。其他结局指标包括额外的肺量计参数、使用圣乔治呼吸问卷（SGRQ）评估的健康状况、通过过渡性呼吸困难指数（TDI）评估的呼吸困难、急救药物使用情况以及患者通过电子日记报告的COPD症状。同时也评估了安全性。在随机分组的432例患者中（格隆溴铵组，n = 216；安慰剂组，n = 216），96%完成了计划的治疗阶段。该研究达到了其主要目标（格隆溴铵组在FEV AUC方面优于安慰剂组）。与安慰剂相比，格隆溴铵在肺功能参数方面有显著改善（<0.001）。在12周内与安慰剂相比，格隆溴铵在健康状况（SGRQ总分和COPD评估测试）、急救药物使用和每日COPD总症状评分方面有显著改善。虽然格隆溴铵和安慰剂在改善呼吸困难方面均有效果，但治疗差异无统计学意义。总体而言，两组之间不良事件和严重不良事件发生率的差异不具有临床意义。未报告死亡病例。对于中重度气流受限的COPD患者，每日两次吸入15.6μg格隆溴铵与安慰剂相比，在肺功能、COPD症状、健康状况和急救药物使用方面显示出具有统计学意义和临床意义的改善。
NCT01715298。
