Clinical trial NCT00857766: A 16-Week Study to Evaluate the Effect of Advair DISKUS™ 250/50mcg on Arterial Stiffness in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Chronic Obstructive Pulmonary Disease
arterial stiffness
Computed Tomography
pulse wave velocity
Pulse wave analysis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-03-09
Enrollment: 249
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Mean Change From Baseline in Aortic Pulse Wave Velocity (aPWV) at the 12-Week Endpoint
timeFrame: Baseline and the 12-Week Endpoint (up to Week 12)
Secondary outcomes:
measure: Mean Change From Baseline in Augmentation Index (AIx) at the 12-Week Endpoint
timeFrame: Baseline and the 12-Week Endpoint (up to Week 12)
measure: Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at the 12-Week Endpoint
timeFrame: Baseline and the 12-Week Endpoint (up to Week 12)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Jasper
country: United States
facility: GSK Investigational Site
state: Alabama
city: Mobile
country: United States
facility: GSK Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Torrance
country: United States
facility: GSK Investigational Site
state: California
city: Hartford
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Coeur D'Alene
country: United States
facility: GSK Investigational Site
state: Idaho
city: Sunset
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Chesterfield
country: United States
facility: GSK Investigational Site
state: Missouri
city: St. Charles
country: United States
facility: GSK Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Downington
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Gaffney
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Union
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Johnson City
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Morgantown
country: United States
facility: GSK Investigational Site
state: West Virginia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.