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

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

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)

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.

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.

Chronic Obstructive Pulmonary Disease, arterial stiffness, Computed Tomography, pulse wave velocity, Pulse wave analysis

Subjects receive blinded Fluticasone Propionate/Salmeterol. At 4 months subjects will receive open label SPIRIVA HANDIHALER

Subjects will receive placebo ADVAIR DISKUS. At 4 months subjects will receive open label SPIRIVA HANDIHALER

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.

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.

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.

FEV1 is a measure of air flow via spirometry. Change from Baseline was calculated as the Endpoint value minus the Baseline Value.

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).

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Dransfield MT, Cockcroft JR, Townsend RR, Coxson HO, Sharma SS, Rubin DB, Emmett AH, Cicale MJ, Crater GD, Martinez FJ. Effect of fluticasone propionate/salmeterol on arterial stiffness in patients with COPD. Respir Med. 2011 Sep;105(9):1322-30. doi: 10.1016/j.rmed.2011.05.016. Epub 2011 Jun 22.

Bhatt SP, Cole AG, Wells JM, Nath H, Watts JR, Cockcroft JR, Dransfield MT. Determinants of arterial stiffness in COPD. BMC Pulm Med. 2014 Jan 4;14:1. doi: 10.1186/1471-2466-14-1.

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.