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Respiratory Research
Published in: Respiratory Research 1/2022

Open Access 01-12-2022 | Magnetic Resonance Imaging | Research

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

Authors: Dave Singh, Jim M. Wild, Dinesh Saralaya, Rod Lawson, Helen Marshall, Jonathan Goldin, Matthew S. Brown, Konstantinos Kostikas, Kristin Belmore, Robert Fogel, Francesco Patalano, Anton Drollmann, Surendra Machineni, Ieuan Jones, Denise Yates, Hanns-Christian Tillmann

Published in: Respiratory Research | Issue 1/2022

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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).
Appendix
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Metadata
Title
Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial
Authors
Dave Singh
Jim M. Wild
Dinesh Saralaya
Rod Lawson
Helen Marshall
Jonathan Goldin
Matthew S. Brown
Konstantinos Kostikas
Kristin Belmore
Robert Fogel
Francesco Patalano
Anton Drollmann
Surendra Machineni
Ieuan Jones
Denise Yates
Hanns-Christian Tillmann
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2022
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-022-01949-3

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