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

This study has been terminated.
(Sponsor decided to stop the study due to expiration of blinded placebo .)
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bartolome Celli, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01760304
First received: October 23, 2012
Last updated: January 7, 2013
Last verified: January 2013
  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

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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
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<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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01760304

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
AstraZeneca
Investigators
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
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Formoterol
Budesonide
Symbicort
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 18, 2014