Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial

Respir Res. 2022 Feb 10;23(1):26. doi: 10.1186/s12931-022-01949-3.

Abstract

Rationale: The long-acting β2-agonist/long-acting muscarinic antagonist combination indacaterol/glycopyrronium (IND/GLY) elicits bronchodilation, improves symptoms, and reduces exacerbations in COPD. Magnetic resonance imaging (MRI) of the lung with hyperpolarized gas and gadolinium contrast enhancement enables assessment of whole lung functional responses to IND/GLY.

Objectives: The primary objective was assessment of effect of IND/GLY on global ventilated lung volume (%VV) versus placebo in COPD. Lung function, regional ventilation and perfusion in response to IND/GLY were also measured.

Methods: This double-blind, randomized, placebo-controlled, crossover study assessed %VV and pulmonary perfusion in patients with moderate-to-severe COPD after 8 days of once-daily IND/GLY treatment (110/50 µg) followed by 8 days of placebo, or vice versa, using inhaled hyperpolarized 3He gas and gadolinium contrast-enhanced MRI, respectively. Lung function measures including spirometry were performed for each treatment after 8 days.

Measurements and main results: Of 31 patients randomized, 29 completed both treatment periods. IND/GLY increased global %VV versus placebo (61.73% vs. 56.73%, respectively, least squares means treatment difference: 5.00% [90% CI 1.40 to 8.60]; P = 0.025). IND/GLY improved whole lung index of ventilation volume to perfusion volume (V/Q) ratio versus placebo; 94% (90% CI 83 to 105) versus 86% (90% CI 75 to 97; P = 0.047), respectively. IND/GLY showed a trend to improve diffusing capacity for carbon monoxide (DLCO) (+ 0.66 mL/min/mmHg; P = 0.082). By Day 8, forced expiratory volume in 1 s (FEV1) was increased by 0.32 L versus placebo (90% CI 0.26 to 0.38; P < 0.0001), substantiating earlier findings and providing evidence of assay sensitivity for this trial.

Conclusions: IND/GLY improved lung ventilation assessed by 3He MRI after 1 week of treatment. This observation may provide mechanistic support for the symptomatic clinical benefit shown with IND/GLY in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT02634983).

Keywords: Chronic obstructive pulmonary disease; Hyperpolarized 3He gas magnetic resonance imaging; Indacaterol/glycopyrronium; V/Q index; Ventilation volume and perfusion volume; Ventilation/perfusion ratio.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Bronchoconstriction / drug effects*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume / drug effects*
  • Glycopyrrolate / administration & dosage
  • Glycopyrrolate / analogs & derivatives*
  • Humans
  • Indans / administration & dosage*
  • Lung / physiopathology*
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quinolones / administration & dosage*
  • Respiratory Function Tests
  • Retrospective Studies
  • Treatment Outcome
  • Vital Capacity / drug effects*

Substances

  • Drug Combinations
  • Indans
  • Quinolones
  • indacaterol-glycopyrronium combination
  • Glycopyrrolate

Associated data

  • ClinicalTrials.gov/NCT02634983