A 16-Week Study to Evaluate the Effect of Advair DISKUS™ 250/50mcg on Arterial Stiffness in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate in patients with Chronic Obstructive Pulmonary Disease (COPD) if Advair DISKUS™ 250/50mcg BID modifies arterial stiffness which is a measure associated with risk of heart disease.

Detailed Description
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This is a multicenter, randomized, double-blind, placebo controlled study to evaluate the effect of Fluticasone Propionate/Salmeterol DISKUS 250/50mcg (FSC) BID on arterial stiffness in COPD subjects. Following a 1 to 14 day run-in period, approximately 250 subjects will be randomly assigned to double-blind treatment for 12 weeks. After the 12 week treatment period, subjects in both treatment arms will receive open label Tiotropium bromide Handihaler18mcg (Tio)QD for 4 weeks in addition to their continued study drug (either FSC250/50 or placebo). The primary measure of efficacy is Pulse Wave Velocity (PWV) at Endpoint. Secondary efficacy measures include Augmentation Index (AIx), Biomarkers of cardiovascular disease, measures of lung function. (e.g. FEV1). Safety will be assessed through the collection of adverse events and COPD exacerbations. Exploratory endpoints include the effect of Tiotropium on PWV and AIx when added to placebo or FSC. Treatment groups will be stratified based on current smoking status. There will be a total of 6 study visits (screening, randomization, and after 4, 8, 12 and 16 weeks of treatment). A follow-up phone contact for collection of adverse event and pregnancy information (if applicable) will be conducted approximately 14 days following the last study visit.

Official Title
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A Randomized, Double-Blind, Parallel-Group, 16-Week Study to Evaluate the Effect of Fluticasone Propionate/Salmeterol DISKUS® 250/50mcg BID and Placebo on Arterial Stiffness in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: ADVAIR DISKUS™ 250/50mcg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written informed consent obtained from the subject and/or subject's legally acceptable representative prior to study participation. Males or females greater then or equal to 50 years of age. A post-albuterol FEV1/FVC ratio of < or equal to 0.70 A post-albuterol FEV1 < 80% of predicted normal. Patients can be current or fomer smoker and must have a cigarette smoking history of > greater then or equal to 10 pack-years . Exclusion Criteria: A current diagnosis of asthma A body mass index (BMI) of > or equal to 35kg/m2 A respiratory diagnosis other than COPD (e.g., lung cancer, bronchiectasis, sarcoidosis, tuberculosis, lung fibrosis).

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ADVAIR DISKUS<br>Subjects receive blinded Fluticasone Propionate/Salmeterol. At 4 months subjects will receive open label SPIRIVA HANDIHALER | Drug: ADVAIR DISKUS™ 250/50mcg<br>* ADVAIR DISKUS™ 250/50mcg is indicated for the twice-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. ADVAIR DISKUS™ 250/50mcg is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations.<br>|
| Placebo Comparator: Placebo<br>Subjects will receive placebo ADVAIR DISKUS. At 4 months subjects will receive open label SPIRIVA HANDIHALER | Other: Placebo<br>* COPD subjects-Placebo DISKUS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Aortic Pulse Wave Velocity (aPWV) at the 12-Week Endpoint | The 12-week Endpoint is defined as the last scheduled measurement of PWV during the 12-week double-blind treatment period (from Visits 3-5; Weeks 4, 8, and 12, respectively), and Baseline is defined as the PWV measure from Visit 2 (Randomization). Change from Baseline was calculated as the Endpoint value minus the Baseline Value. PWV is used as a measure of arterial stiffness, which is a measure of the cushioning functioning of major vessels like the aorta. The velocity of the PW along an artery is dependent on the stiffness of that artery. | Baseline and the 12-Week Endpoint (up to Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Augmentation Index (AIx) at the 12-Week Endpoint | AIx is a surrogate measure of peripheral (not aortic) arterial resistance and is measured by analysis of the pulse wave at the radial artery. AIx = ([delta P/Pulse Pressure] x 100); delta P is defined by a notch near the peak of the pulse wave. Change from Baseline was calculated as the Endpoint value minus the Baseline Value. | Baseline and the 12-Week Endpoint (up to Week 12) | 
| Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at the 12-Week Endpoint | FEV1 is a measure of air flow via spirometry. Change from Baseline was calculated as the Endpoint value minus the Baseline Value. | Baseline and the 12-Week Endpoint (up to Week 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, arterial stiffness, Computed Tomography, pulse wave velocity, Pulse wave analysis