The Effect of BEVESPI AEROSPHERE ® Therapy on Exercise Tolerance in COPD
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 4

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.
    

Detailed 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.
    

Intervention name(s): Glycopyrrolate / Formoterol
Intervention type(s): Drug
Intervention description(s): Exercise Tolerance
Other intervention name(s): Bevespi Aerosphere
Intervention MeSH terms: Glycopyrrolate; Formoterol Fumarate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: chronic obstructive pulmonary disease (COPD); exercise intolerance; dynamic hyperinflation