State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Global Clinical Development, Chiesi Farmaceutici SpA, Largo Belloli, 11\a, 43122, Parma, Italy.
Respir Res. 2021 Mar 23;22(1):90. doi: 10.1186/s12931-021-01683-2.
A single-inhaler extrafine triple combination of beclometasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) has been developed for maintenance therapy of chronic obstructive pulmonary disease (COPD). This study evaluated the efficacy and safety of BDP/FF/G in patients in three eastern Asian areas: China, Republic of Korea and Taiwan.
TRIVERSYTI was a double-blind, randomised, active-controlled, parallel-group study in patients with COPD, post-bronchodilator forced expiratory volume in 1 s (FEV) < 50% predicted, ≥ 1 exacerbation in the previous 12 months, and receiving inhaled maintenance medication. Patients received either extrafine BDP/FF/G 100/6/10 µg via pressurised metered-dose inhaler, or non-extrafine budesonide/formoterol (BUD/FF) 160/4.5 µg via dry-powder inhaler, both administered as two puffs twice-daily for 24 weeks. The co-primary objectives (analysed in the overall population) were to demonstrate superiority of BDP/FF/G over BUD/FF for change from baseline in pre-dose morning and 2-h post-dose FEV at Week 24 (these were analysed as key secondary objectives in the China subgroup). The rate of moderate/severe COPD exacerbations was a secondary endpoint.
Of 708 patients randomised, 88.8% completed. BDP/FF/G was superior to BUD/FF for pre-dose and 2-h post-dose FEV at Week 24 [adjusted mean differences 62 (95% CI 38, 85) mL and 113 (87, 140) mL; both p < 0.001]. The annualised moderate/severe exacerbation rate was 43% lower with BDP/FF/G [rate ratio 0.57 (95% CI 0.42, 0.77); p < 0.001]. Adverse events were reported by 61.1% and 67.0% patients with BDP/FF/G and BUD/FF. Results were similar in the China subgroup.
In patients with COPD, FEV < 50% and an exacerbation history despite maintenance therapy, treatment with extrafine BDP/FF/G improved bronchodilation, and was more effective at preventing moderate/severe COPD exacerbations than BUD/FF. Trial registration CFDA CTR20160507 (registered 7 Nov 2016, http://www.chinadrugtrials.org.cn/index.html ).
布地奈德双丙酸酯（BDP）、富马酸福莫特罗（FF）和格隆溴铵（G）三联精细干粉吸入剂已被开发用于慢性阻塞性肺疾病（COPD）的维持治疗。这项研究评估了 BDP/FF/G 在东亚三个地区（中国、韩国和中国台湾）的 COPD 患者中的疗效和安全性。
TRIVERSYTI 是一项在 COPD 患者中进行的双盲、随机、活性对照、平行分组研究，这些患者在支气管扩张剂后用力呼气量（FEV）<预测值的 50%、过去 12 个月中有≥1 次加重且接受吸入性维持治疗。患者接受布地奈德双丙酸酯/福莫特罗（BDP/FF）精细干粉 100/6/10μg（通过压力定量气雾剂）或非精细干粉布地奈德/福莫特罗（BUD/FF）160/4.5μg（通过干粉吸入器），均每日两次各两喷，持续 24 周。主要共同终点（在总体人群中进行分析）是证明 BDP/FF/G 优于 BUD/FF，在第 24 周时的清晨预剂量和 2 小时后剂量的 FEV 变化（这些在亚组中国患者中被分析为关键次要终点）。中度/重度 COPD 加重的发生率是次要终点。
在 708 名随机患者中，88.8%完成了研究。BDP/FF/G 优于 BUD/FF，在第 24 周时的清晨预剂量和 2 小时后剂量的 FEV 有显著改善[调整后的平均差异分别为 62（95%CI 38，85）mL 和 113（87，140）mL；均 P<0.001]。BDP/FF/G 使中度/重度 COPD 加重的年化发生率降低了 43%[发生率比 0.57（95%CI 0.42，0.77）；P<0.001]。BDP/FF/G 和 BUD/FF 组分别有 61.1%和 67.0%的患者报告了不良事件。在中国亚组中也观察到了类似的结果。
在 COPD 患者中，FEV<50%且尽管维持治疗仍有加重史，使用精细 BDP/FF/G 可改善支气管扩张，并比 BUD/FF 更有效地预防中度/重度 COPD 加重。试验注册 CFDA CTR20160507（于 2016 年 11 月 7 日注册，http://www.chinadrugtrials.org.cn/index.html）。
