The Effect of BEVESPI AEROSPHERE ® Therapy on Exercise Tolerance in COPD

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title: An Investigator Initiated, Randomized, Double Blind, Placebo Controlled Study to Assess the Effect of Glycopyrrolate/Formoterol on Exercise Tolerance and Dynamic Hyperinflation in Patients With Chronic Obstructive Pulmonary Disease.

Status Completed

Clinical Trial Summary

This trial is an investigator initiated study involving the use of the AstraZenica Aerophere Inhaler (Glycopyrrolate/Formoterol) to determine the effect on exercise tolerance and dynamic hyperinflation in patients with chronic obstructive lung disease.

Clinical Trial Description

Patients with chronic obstructive pulmonary disease (COPD) have obstruction to expiratory airflow, marked breathlessness, high dyspnea scores, and reduced exercise tolerance relative to age and gender matched non-smoking controls (Casaburi, 2009; Casaburi et al., 2014; Puente-Maestu et al., 2016). A prominent mechanism for exercise intolerance is thought to be dynamic hyperinflation during exercise (an increase in the end-expiratory lung volume) that contributes to the sensation of breathlessness, and ultimately results in early cessation of exercise. A co-maladaptive mechanism of exercise limitation in COPD is related to wasted or excessive ventilation at all work intensities from increased dead space ventilation relative to total ventilation (increased VD/VT). This requirement for additional ventilation limits exercise capacity and contributes to dynamic hyperinflation and ventilatory limitation (O'Donnell et al., 2004). Treatment with individual bronchodilators, including short acting beta agonists (SABA), long acting beta agonists (LABA), short acting muscarinic antagonists (SAMA) and long acting muscarinic antagonists (LAMA) is effective in partially reversing the expiratory airflow obstruction at rest and during exercise resulting in reduced dynamic hyperinflation. Because beta-agonists and anticholinergics broncho-dilate synergistically, they are often used in combination products (SABA+SAMA or LABA/LAMA). The optimal sustained bronchodilation effect in COPD appears to be achieved by fixed dose, long acting combination medications (LABA/LAMA). (Bateman et al., 2014; Casaburi, 2009; Casaburi et al., 2014; Cope et al., 2013; Huisman et al., 2015). As dynamic hyperinflation appears to also be a limiting factor in exercise tolerance, and LABA/LAMA preparations improve airflow during exercise, it appears likely that use of a fixed-dose combination bronchodilator, BEVESPI AEROSPHERE ® (Glycopyrrolate/Formoterol) will increase exercise tolerance and reduce hyperinflation in COPD patients. We hypothesize that exercise tolerance in a constant work rate, high intensity cardiopulmonary exercise test will be increased with BEVESPI AEROSPHERE ® (Glycopyrrolate/Formoterol), and that the increase in exercise tolerance will be mediated by a combination of: 1. reduced dynamic hyperinflation, and 2. decreased dead space ventilation (VD/VT) during exercise. Primary objective: To determine the magnitude of exercise time improvement (seconds) with BEVESPI AEROSPHERE ® (Glycopyrrolate/Formoterol) relative to placebo during high intensity, constant work rate exercise in COPD patients. Secondary objective: To determine if the VD/VT can be reliably assessed during constant work rate exercise using transcutaneous CO2 measurement (tcpCO2) and, if so, if BEVESPI AEROSPHERE ® (Glycopyrrolate/Formoterol) results in a reduction in VD/VT relative to placebo at isotime during high intensity constant work rate exercise in COPD patients. Tertiary objective: To determine if computerized assessment of the spontaneous expiratory flow-volume loop during exercise can provide additional information about both dynamic hyperinflation and the effects of BEVESPI AEROSPHERE ® (Glycopyrrolate/Formoterol) during high intensity, constant work rate exercise in COPD patients. ;

Related Conditions & MeSH terms

• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

• NCT number: NCT03081156
• Study type: Interventional
• Source: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Status: Completed
• Phase: Phase 4
• Start date: March 27, 2017
• Completion date: January 31, 2019