Clinical trial NCT01760304
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: COPD
Sponsor: Brigham and Women's Hospital
Start date: 2012-01-01; Completion date: 2012-10-01
Enrollment: 5 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
To investigate whether Budesonide/Formoterol (Symbicort ®) therapy can improve heart function at rest by decreasing lung hyperinflation in patients with COPD (Chronic Obstructive Pulmonary Disease).

Detailed description:
Patients with moderate to advanced COPD are known to have static hyperinflation (at rest) as a consequence of expiratory flow limitation. Hyperinflation is easily detected by measuring lung volumes during standard pulmonary function testing.

Decreased Inspiratory Capacity (IC) secondary to hyperinflation has been described as a predictor of mortality in COPD, and as a limiting factor for the maximal tidal volume attained during exercise. Hyperinflation has been linked to a low cardiac output in part by limiting left ventricular ejection fraction during exercise.

Treatment with inhaled anticholinergic agents or long-acting beta agonists (LABA) and combination of the LABA formoterol and budesonide has been shown to improve IC and decrease lung hyperinflation. Bronchodilators have been shown to improve exercise endurance in COPD when combined with pulmonary rehabilitation, however the exact mechanism: improvement of lung mechanics and /or improvement in cardiac function is not well known.

Impedance cardiography (ICG) has emerged as a method to measure cardiac output without the need for invasive devices. Cardiac output measurement by impedance cardiography (CO-ICG) is a valid and reproducible method. It has been shown to have good correlation with thermodilution and the direct Fick method for the measurement of stroke volume and cardiac output.

In addition, the oxygen pulse, easily obtained by dividing the measured oxygen uptake by the heart rate (VO2/HR) provides an adequate reflection of cardiac stroke volume when the systemic extraction of oxygen is stable.

This method has been used to evaluate the effect of static and dynamic hyperinflation on cardiac function.

This pilot study is designed to be a single center (Brigham and Women's Hospital), randomized, placebo-controlled, double blind, crossover study of 14 patients (male and female 40 to 80 years old) with COPD and static hyperinflation.

The primary endpoint is the measurement of stroke volume, cardiac output and oxygen pulse at rest before and after the administration of budesonide/formoterol compared to placebo.

Arms: arm 1: This is a crossover study, where every patient will receive in a blinded fashion either Budesonide/Formoterol (Symbicort ® ) or placebo arm 2: This is a crossover study, where every patient will receive in a blinded fashion either Budesonide/Formoterol (Symbicort ® ) or placebo
Interventions: intervention 1: Budesonide / Formoterol intervention 2: Placebo
Intervention descriptions: intervention 1: Budesonide/ formoterol (B/F) 160/4.5 mcg per activation. Subject who met inclusion criteria will be have at each visit day lung function, heart function and breathlessness measurements at baseline, then they will receive 2 puffs of either Budesonide/formoterol (B/F) 160/4.5 mcg per activation (as per the randomization-crossover schema).

After 45 minutes , the above measurements will be repeated. intervention 2: Each visit day lung function, heart function and breathlessness measurements at baseline, then they will receive 2 puffs of placebo (as per the randomization-crossover schema).

After 45 minutes , the above measurements will be repeated.

Protocol documents: