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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00857766
• Other study ID #: 112355
• Status: Completed
• Phase: Phase 4
• First received: March 5, 2009
• Last updated: October 18, 2012
• Start date: March 2009
• Est. completion date: March 2010

Study information

• Verified date: December 2011
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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).

Study Design

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

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• ADVAIR DISKUS™ 250/50mcg
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.

Other:
• Placebo
COPD subjects-Placebo DISKUS

Locations

Country	Name	City	State
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Chesterfield	Missouri
United States	GSK Investigational Site	Coeur D'Alene	Idaho
United States	GSK Investigational Site	Downington	Pennsylvania
United States	GSK Investigational Site	Gaffney	South Carolina
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Hartford	Connecticut
United States	GSK Investigational Site	Jasper	Alabama
United States	GSK Investigational Site	Johnson City	Tennessee
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Mobile	Alabama
United States	GSK Investigational Site	Morgantown	West Virginia
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	St. Charles	Missouri
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	Sunset	Louisiana
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	Union	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No