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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: ADVAIR DISKUS™ 250/50mcg; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • GSK Investigational Site
    • Jasper, Alabama, United States, 35501
      • GSK Investigational Site
    • Mobile, Alabama, United States, 36608
      • GSK Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • GSK Investigational Site
  • California
    • San Diego, California, United States, 92103-8415
      • GSK Investigational Site
    • Torrance, California, United States, 90505
      • GSK Investigational Site
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • GSK Investigational Site
  • Idaho
    • Coeur D'Alene, Idaho, United States, 83814
      • GSK Investigational Site
  • Louisiana
    • Sunset, Louisiana, United States, 70584
      • GSK Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • GSK Investigational Site
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • GSK Investigational Site
    • St. Charles, Missouri, United States, 63301
      • GSK Investigational Site
    • St. Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • GSK Investigational Site
  • Pennsylvania
    • Downington, Pennsylvania, United States, 19335
      • GSK Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • GSK Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406-7108
      • GSK Investigational Site
    • Gaffney, South Carolina, United States, 29340
      • GSK Investigational Site
    • Greenville, South Carolina, United States, 29615
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
    • Union, South Carolina, United States, 29379
      • GSK Investigational Site
  • Tennessee
    • Johnson City, Tennessee, United States, 37601
      • GSK Investigational Site
  • Washington
    • Spokane, Washington, United States, 99204
      • GSK Investigational Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ADVAIR DISKUS; Subjects receive blinded Fluticasone Propionate/Salmeterol. At 4 months subjects will receive open label SPIRIVA HANDIHALER	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.
Placebo Comparator: Placebo; Subjects will receive placebo ADVAIR DISKUS. At 4 months subjects will receive open label SPIRIVA HANDIHALER	Other: Placebo; COPD subjects-Placebo DISKUS

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: March 5, 2009
• First Submitted That Met QC Criteria: March 5, 2009
• First Posted (Estimate): March 9, 2009

Study Record Updates

• Last Update Posted (Estimate): January 30, 2017
• Last Update Submitted That Met QC Criteria: December 1, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Pulse wave analysis; Chronic Obstructive Pulmonary Disease; pulse wave velocity; arterial stiffness; Computed Tomography
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Sympathomimetics; Fluticasone-Salmeterol Drug Combination
• Other Study ID Numbers: 112355

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Annotated Case Report Form
   Information identifier: 112355
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 112355
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 112355
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 112355
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 112355
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 112355
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 112355
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register