Velocity Clinical Research Grosshansdorf, Airway Research Center North (ARCN), Formerly Pulmonary Research Institute at Lung Clinic Grosshansdorf, Member of the German Center for Lung Research (DZL), Wöhrendamm 80, 22927, Grosshansdorf, Germany.
Velocity Clinical Research Lübeck, Formerly KLB Gesundheitsforschung Lübeck GmbH, Lübeck, Germany.
Respir Res. 2024 Oct 17;25(1):378. doi: 10.1186/s12931-024-02993-x.
The single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) is available for maintenance therapy of chronic obstructive pulmonary disease (COPD). Cardinal features of COPD are lung hyperinflation and reduced exercise capacity. TRIFORCE aimed to evaluate the effect of BDP/FF/G on lung hyperinflation and exercise capacity in patients with COPD.
This double-blind, randomised, active- and placebo-controlled, crossover study recruited adults with COPD aged ≥ 40 years, who were hyperinflated and symptomatic, and were receiving mono- or dual inhaled maintenance COPD therapy. In the three treatment periods, patients were randomised to receive BDP/FF/G, BDP/FF, or placebo, each for 3 weeks, with a 7-10-day washout between treatment periods. Assessments included slow inspiratory spirometry (for resting inspiratory capacity [IC]) and constant work-rate cycle ergometry (for dynamic IC and exercise endurance time). The primary objective was to compare BDP/FF/G and BDP/FF vs. placebo for resting IC at Week 3. Key secondary objectives were to compare BDP/FF/G and BDP/FF vs. placebo for dynamic IC and exercise endurance time during constant work rate cycle ergometry at Week 3.
Of 106 patients randomised, 95 completed the study. Resting IC adjusted mean differences vs. placebo were 315 and 223 mL for BDP/FF/G and BDP/FF, respectively (p < 0.001 for both). Adjusted mean differences vs. placebo for the key secondary endpoints were: 245 mL for dynamic IC (p < 0.001) and 69.2 s for exercise endurance time (nominal p < 0.001) with BDP/FF/G, and 96 mL (p = 0.053) and 70.1 s (nominal p < 0.001) with BDP/FF. Differences between BDP/FF/G and BDP/FF for resting and dynamic IC were 92 and 149 mL (p < 0.01 for both). All three treatments were generally well tolerated, with 27.3%, 25.3% and 19.0% of patients reporting adverse events with BDP/FF/G, BDP/FF and placebo, respectively, all mild or moderate.
In patients with COPD, BDP/FF/G provided significant and clinically relevant improvements vs. placebo and BDP/FF in static and dynamic hyperinflation, with an improvement vs. placebo in exercise endurance.
ClinicalTrials.gov (NCT05097014), registered 27th October 2021.
倍氯米松二丙酸酯、富马酸福莫特罗和格隆溴铵的单一吸入三联组合（BDP/FF/G）可用于慢性阻塞性肺疾病（COPD）的维持治疗。COPD 的主要特征是肺过度充气和运动能力下降。TRIFORCE 旨在评估 BDP/FF/G 对 COPD 患者肺过度充气和运动能力的影响。
这项双盲、随机、阳性和安慰剂对照、交叉研究招募了年龄≥40 岁、肺过度充气和有症状的 COPD 成年患者，他们正在接受单药或双联吸入性 COPD 维持治疗。在三个治疗期内，患者被随机分配接受 BDP/FF/G、BDP/FF 或安慰剂，每个治疗期为 3 周，每个治疗期之间有 7-10 天的洗脱期。评估包括缓慢吸气肺活量测定（用于静息吸气容量 [IC]）和恒功率踏车运动试验（用于动态 IC 和运动耐力时间）。主要目标是比较 BDP/FF/G 和 BDP/FF 与安慰剂在第 3 周时的静息 IC。主要次要目标是比较 BDP/FF/G 和 BDP/FF 与安慰剂在第 3 周时的恒功率踏车运动试验中的动态 IC 和运动耐力时间。
在 106 名随机患者中，95 名完成了研究。与安慰剂相比，BDP/FF/G 和 BDP/FF 的静息 IC 调整平均差异分别为 315 和 223 mL（均 p<0.001）。与安慰剂相比，关键次要终点的调整平均差异分别为：245 mL 用于动态 IC（p<0.001）和 69.2 s 用于运动耐力时间（名义 p<0.001），BDP/FF/G 为 96 mL（p=0.053）和 70.1 s（名义 p<0.001），BDP/FF。BDP/FF/G 和 BDP/FF 之间的静息和动态 IC 差异分别为 92 和 149 mL（均 p<0.01）。三种治疗均普遍耐受良好，BDP/FF/G、BDP/FF 和安慰剂组分别有 27.3%、25.3%和 19.0%的患者报告不良事件，均为轻度或中度。
在 COPD 患者中，BDP/FF/G 与安慰剂和 BDP/FF 相比，在静态和动态过度充气方面提供了显著和有临床意义的改善，与安慰剂相比，运动耐力也有所改善。
ClinicalTrials.gov（NCT05097014），2021 年 10 月 27 日注册。
