Changes in Cardiac Function in COPD Patients After Administration of Budesonide/Formoterol (Symbicort®) Versus Placebo

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— AZCO  

Official title:

Evaluation of Changes in Cardiac Function in COPD Patients With Resting Hyperinflation After Administration of Budesonide/Formoterol (Symbicort®) Compared With Placebo

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01760304
• Other study ID #: 2011-P-001576/1
• Secondary ID: D589BL00021/ISSS
• Status: Terminated
• Phase: Phase 4
• First received: October 23, 2012
• Last updated: January 7, 2013
• Start date: January 2012
• Est. completion date: October 2012

Study information

• Verified date: January 2013
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: October 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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:

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac output	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	Change from Baseline after administration of study medication on week 1, 2, 3 & 4	No
Secondary	Lung hyperinflation	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.	Change from Baseline after administration of study medication on week 1, 2, 3 & 4	No
Secondary	Evaluation of breathlessness	Evaluation of dyspnea using the Visual Analog Scale (VAS), the Breathlessness, Cough, and Sputum Scale (BCSS) and the Modified Medical Research Council (MMRC) scale	Change from Baseline after administration of study medication on week 1, 2, 3 & 4	No
Secondary	Evaluation of respiratory and heart function derived from primary outcome	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	Change from Baseline after administration of study medication on week 1, 2, 3 & 4	No
Secondary	Handgrip strength	Evaluate the relationship between cardiac output and handgrip strength (Correlation of myocardial function and peripheral muscle strength)	at baseline and on week 1, 2, 3 & 4	No