Respiratory Research | |
Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial | |
Jim M. Wild1  Helen Marshall1  Jonathan Goldin2  Matthew S. Brown3  Dave Singh4  Rod Lawson5  Surendra Machineni6  Denise Yates7  Kristin Belmore7  Hanns-Christian Tillmann8  Anton Drollmann9  Francesco Patalano9  Ieuan Jones9  Robert Fogel1,10  Dinesh Saralaya1,11  Konstantinos Kostikas1,12  | |
[1] Imaging Sciences, Department of Infection, Immunity and Cardiovascular Disease, POLARIS, University of Sheffield, Sheffield, UK;MedQIA, Los Angeles, CA, USA;MedQIA, Los Angeles, CA, USA;Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA;Medicines Evaluation Unit, University of Manchester, Manchester University National Health Service Foundation Trust, Manchester, UK;National Institute for Health Research, Sheffield Clinical Research Facility, Sheffield, UK;Novartis Healthcare Pvt, Ltd, Hyderabad, India;Novartis Institutes for Biomedical Research, Cambridge, MA, USA;Novartis Institutes for Biomedical Research, Fabrikstrasse 2, Novartis Campus, 4056, Basel, Switzerland;Novartis Pharma AG, Basel, Switzerland;Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA;Respiratory Clinical Trials Unit, Bradford Teaching Hospitals National Health Service Foundation Trust, Bradford, UK;University of Ioannina Medical School, Ioannina, Greece; | |
关键词: Chronic obstructive pulmonary disease; Hyperpolarized He gas magnetic resonance imaging; Indacaterol/glycopyrronium; Ventilation volume and perfusion volume; Ventilation/perfusion ratio; V/Q index; | |
DOI : 10.1186/s12931-022-01949-3 | |
来源: Springer | |
【 摘 要 】
RationaleThe 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.ObjectivesThe 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.MethodsThis 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 resultsOf 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.ConclusionsIND/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).
【 授权许可】
CC BY
【 预 览 】
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