Clinical trial NCT01760304: Changes in Cardiac Function in COPD Patients After Administration of Budesonide/Formoterol (Symbicort®) Versus Placebo
Official title: Evaluation of Changes in Cardiac Function in COPD Patients With Resting Hyperinflation After Administration of Budesonide/Formoterol (Symbicort®) Compared With Placebo
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: COPD
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2013-01-04
Enrollment: 5
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

Outpatients subjects of either sex between ages 40-80 years, with a diagnosis of COPD. COPD will be characterized as the presence of airflow obstruction with an FEV1/FVC \< 0.7 (Forced Expiratory Volume at one second / Forced Vital Capacity) and a FEV1 (Forced Expiratory Volume at one second ) 80% of predicted. All patients must have lung hyperinflation as demonstrated by an increase of ≥100 ml after the administration of budesonide/formoterol. All patients must have a cigarette smoking history of more than 10 pack-years, and be able to perform all the specified procedures as required by the protocol.

Exclusion Criteria:

1. Patients with other significant diseases (recent \< 6 weeks COPD exacerbation) that could place the patient at risk because of participation in the study, or which may influence the results of the study or the patients' ability to participate in the study.
2. All patients with a recent (\<1 year) history of myocardial infarction, or with a recent history of heart failure (NYHA class III and IV, pulmonary edema, or patients with cardiac arrhythmias.
3. Patients on daytime oxygen therapy.
4. Patients with known active tuberculosis.
5. Patients with a history of active cancer except for non-metastatic skin cancer.
6. Patients who have undergone thoracotomy, sternotomy, major cardiopulmonary intervention (lung resection, open heart surgery, etc), or other procedure in the 6 months prior to evaluation likely to cause instability of pulmonary status.
7. Patients with upper respiratory infection in the past six weeks.

Primary outcomes:
measure: Cardiac Output
timeFrame: Change from Baseline and at 45 minutes after administration of study medication or placebo
Secondary outcomes:
measure: Lung Hyperinflation
timeFrame: Change from Baseline and after 45 minutes after administration of study medication or placebo
measure: Evaluation of O2 Pulse
timeFrame: Change from Baseline and 45 minutes after administration of study medication or placebo
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Bartolome R Celli, MD
role: PRINCIPAL_INVESTIGATOR
References: