Effects of Dual Bronchodilator Treatment on Cardiopulmonary Interactions in COPD

• Status: Completed
• Trial end date: 2018-06-30
• Target enrollment: 0
• Participant gender: All

Summary

The deleterious consequences of lung hyperinflation seem not to be restricted to the respiratory system in patients with chronic obstructive pulmonary disease (COPD). Cardiac function, in particular, is strongly influenced by changes in lung volumes and intra-thoracic pressures. In this context, strategies to reduce lung hyperinflation and the work of breathing can positively impact upon cardiac output and blood flow redistribution to peripheral muscles in these patients. There is growing evidence that combination of bronchodilators of different classes is an efficacious and safe strategy for further improving airflow obstruction and hyperinflation in patients with more advanced COPD. Therefore, we aim to investigate that, compared with placebo, a novel LABA/LAMA fixed combination (tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® (Inspiolto®) (TIO/OLO) would decrease lung volumes at rest and during exercise, thereby improving: 1) central and peripheral hemodynamics and 2) arterial oxygenation, with positive consequences on skeletal muscle oxygenation and exercise tolerance in hyperinflated patients with moderate to very severe COPD.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Queen's University
• Collaborator: Boehringer Ingelheim
• Treatments: Bronchodilator Agents; Olodaterol; Tiotropium Bromide

Criteria

Inclusion Criteria:

1. Age ≥50 years;

2. Male or female gender;

3. Long-term history of active smoking;

4. Signs and symptoms of COPD with adequate treatment according to the GOLD recommendations for at least 3 months (1);

5. A modified MRC dyspnea score ≥2 or a Baseline Dyspnea Index ≤8;

6. Resting lung hyperinflation as demonstrated by inspiratory capacity <80% predicted or functional residual capacity >120% predicted at Visit 1;

7. Objective evidence of dynamic hyperinflation (a decrease in inspiratory capacity from rest >200 mL)(24,25) and peak exercise dyspnea (breathing discomfort) ≥ leg discomfort scores during the incremental cardiopulmonary exercise test at Visit 1;

8. A positive "volume" response (≥200 mL increase in inspiratory capacity) to a bronchodilator (400μg salbutamol) at Visit 1

9. Ability to perform all study procedures and provide/sign informed consent.

Exclusion Criteria:

1. Asthma or other concomitant pulmonary disease;

2. Use of oral steroids in the preceding month;

3. Orthopedic/rheumatological limitation precluded cycling;

4. Type I or non-controlled type II diabetes mellitus or other endocrine diseases;

5. Unstable angina, life-threatening cardiac arrhythmias, use of an implantable defibrillator;

6. Myocardial infarction within the previous 6 months;

7. History of long QT syndrome (or prolonged corrected QT interval (>450 ms during screening);

8. Clinically significant ECG abnormality;

9. History of exercise-induced syncope;

10. Any contraindication for exercise testing;

11. Inability to understand and cooperate with the procedures.