Changes in Cardiac Function in COPD Patients After Administration of Budesonide/Formoterol (Symbicort®) Versus Placebo (AZCO)
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Purpose
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).
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Obstructive Pulmonary Disease (COPD) |
Drug: Budesonide / Formoterol Drug: Placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Evaluation of Changes in Cardiac Function in COPD Patients With Resting Hyperinflation After Administration of Budesonide/Formoterol (Symbicort®) Compared With Placebo |
- Cardiac output [ Time Frame: Change from Baseline after administration of study medication on week 1, 2, 3 & 4 ] [ Designated as safety issue: No ]Impedance cardiography (ICG) (BioZ Dx ICG machine, by CardioDynamics) will be used to measure cardiac output without the need for invasive devices. Cardiac output measurement by impedance cardiography (CO-ICG) is a plethysmography technique of using sensors to detect the properties of the blood flow in the thorax. The placement of four dual disposable sensors on the neck and chest are used to transmit and detect electrical and impedance changes in the thorax, which are used to measure and calculate hemodynamic parameters. 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
- Lung hyperinflation [ Time Frame: Change from Baseline after administration of study medication on week 1, 2, 3 & 4 ] [ Designated as safety issue: No ]Evaluation of lung hyperinflation as determined by Pulmonary function test where Inspiratory Capacity (IC), and End Expiratory Lung Volume (EELV) before and at timed intervals after the administration of the budesonide/formoterol versus placebo.
- Evaluation of breathlessness [ Time Frame: Change from Baseline after administration of study medication on week 1, 2, 3 & 4 ] [ Designated as safety issue: No ]Evaluation of dyspnea using the Visual Analog Scale (VAS), the Breathlessness, Cough, and Sputum Scale (BCSS) and the Modified Medical Research Council (MMRC) scale
- Evaluation of respiratory and heart function derived from primary outcome [ Time Frame: Change from Baseline after administration of study medication on week 1, 2, 3 & 4 ] [ Designated as safety issue: No ]Evaluation of heart rate, blood pressure, respiratory rate, minute ventilation, tidal volume, respiratory rate and oxygen saturation before and at timed intervals after the administration of the budesonide/formoterol VS. placebo
- Handgrip strength [ Time Frame: at baseline and on week 1, 2, 3 & 4 ] [ Designated as safety issue: No ]Evaluate the relationship between cardiac output and handgrip strength (Correlation of myocardial function and peripheral muscle strength)
| Enrollment: | 5 |
| Study Start Date: | January 2012 |
| Study Completion Date: | October 2012 |
| Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Budesonide / Formoterol
This is a crossover study, where every patient will receive in a blinded fashion either Budesonide/Formoterol (Symbicort ® ) or placebo
|
Drug: Budesonide / Formoterol
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. Other Name: Symbicort ®
|
|
Placebo Comparator: Placebo
This is a crossover study, where every patient will receive in a blinded fashion either Budesonide/Formoterol (Symbicort ® ) or placebo
|
Drug: Placebo
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. Other Name: Placebo
|
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| Ages Eligible for Study: | 40 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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<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:
- 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.
- 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.
- Patients on daytime oxygen therapy.
- Patients with known active tuberculosis.
- Patients with a history of active cancer except for non-metastatic skin cancer.
- 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.
- Patients with upper respiratory infection in the past six weeks.
Contacts and Locations| United States, Massachusetts | |
| Brigham and Women's Hospital | |
| Boston, Massachusetts, United States, 02115 | |
| Principal Investigator: | Bartolome R Celli, MD | Brigham and Women's Hospital |
More Information
No publications provided
| Responsible Party: | Bartolome Celli, Lecturer in Medicine, Harvard Medical School, Brigham and Women's Hospital |
| ClinicalTrials.gov Identifier: | NCT01760304 History of Changes |
| Other Study ID Numbers: | 2011-P-001576/1, D589BL00021/ISSSYMB0033 |
| Study First Received: | October 23, 2012 |
| Last Updated: | January 7, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Brigham and Women's Hospital:
|
COPD |
Additional relevant MeSH terms:
|
Lung Diseases Respiration Disorders Pulmonary Disease, Chronic Obstructive Lung Diseases, Obstructive Respiratory Tract Diseases Budesonide Formoterol Symbicort Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Pharmacologic Actions |
Anti-Asthmatic Agents Respiratory System Agents Therapeutic Uses Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Anti-Inflammatory Agents Adrenergic beta-2 Receptor Agonists Adrenergic beta-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 19, 2013