Effects of inhaled beclometasone dipropionate/formoterol fumarate/glycopyrronium vs. beclometasone dipropionate/formoterol fumarate and placebo on lung hyperinflation and exercise endurance in chronic obstructive pulmonary disease: a randomised controlled trial

Respir Res. 2024 Oct 17;25(1):378. doi: 10.1186/s12931-024-02993-x.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov (NCT05097014), registered 27th October 2021.

Keywords: Cycle ergometry; Dual bronchodilation; Fixed-dose combination; Hyperinflation; Triple therapy.

Publication types

  • Randomized Controlled Trial
  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Aged
  • Beclomethasone* / administration & dosage
  • Bronchodilator Agents / administration & dosage
  • Cross-Over Studies*
  • Double-Blind Method
  • Drug Combinations*
  • Exercise Tolerance* / drug effects
  • Exercise Tolerance* / physiology
  • Female
  • Formoterol Fumarate* / administration & dosage
  • Glycopyrrolate* / administration & dosage
  • Humans
  • Lung / drug effects
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / physiopathology
  • Treatment Outcome

Substances

  • Beclomethasone
  • Glycopyrrolate
  • Formoterol Fumarate
  • Drug Combinations
  • Bronchodilator Agents

Associated data

  • ClinicalTrials.gov/NCT05097014