Can Advair and Flovent Reduce Systemic Inflammation Related to Chronic Obstructive Pulmonary Disease (COPD)? A Multi-Center Randomized Controlled Trial

NCT00120978 | Unknown Phase 4

• 1 other identifier: SC0100141
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 10

Brief Summary

Large population-based studies suggest that patients with chronic obstructive pulmonary disease (COPD) are 2 to 3 times at risk for cardiovascular mortality, which accounts for a large proportion of the total number of deaths. How COPD increases the risk of poor cardiovascular outcomes is largely unknown. However, there is growing evidence that persistent low-grade systemic inflammation is present in COPD and that this may contribute to the pathogenesis of atherosclerosis and cardiovascular disease among COPD patients. Inflammation and more specifically, C-reactive protein (CRP), has been linked with all stages of atherosclerosis, including plaque genesis, rupture and subsequent thrombo-fibrosis of vulnerable vessels. Recently, our group has demonstrated in a relatively small study that short-term inhaled corticosteroid (ICS) therapy can repress serum CRP levels in stable COPD patients. Conversely, withdrawal of ICS leads to a marked increase in serum CRP levels. Although very promising, these data cannot be considered definitive because the study was small in size and scope (N=41 patients). Additionally, this study did not address the potential effects of combination therapy with ICS and long-acting β2 agonists (LABA). This is an important short-coming because combination therapy of ICS and LABA have been shown to produce improved clinical outcomes over ICS monotherapy and is commonly used by clinicians in the treatment of moderate to severe COPD. We hypothesize that inhaled fluticasone (Flovent®) reduces systemic inflammation and that combination therapy (Advair®) is more effective than steroids alone in reducing systemic inflammation in COPD. In this proposal, we will implement a randomized controlled trial to determine whether ICS by themselves or in combination with LABAs can:

1. 1.reduce CRP levels in stable COPD patients and
2. 2.reduce other pro-inflammatory cytokines, which have been linked with cardiovascular morbidity and mortality such as interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1)

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Clinical Trial; C-reactive protein; fluticasone; salmeterol

Outcome Measures

Primary Outcomes (1)

• Change in serum C-reactive protein levels over 3 months between treatment groups.

Secondary Outcomes (1)

• changes in serum interleukin levels; quality of life; FEV1 between treatment groups

Interventions

Advair DRUG

Flovent DRUG

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have a clinical diagnosis of chronic obstructive pulmonary disease according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.
• Patients must have a cigarette smoking history of more than 10 pack-years
• Patients must be clinically stable and at least 4 weeks from last acute exacerbation (and return to baseline level of symptoms)
• Patients must have an FEV1 of less than 80% of predicted values with FEV1 to FVC ratio of less than 0.70 (post-bronchodilator values)
• Men or women ≥ 45 years of age

Sponsors & Collaborators

• University of British Columbia: lead
• GlaxoSmithKline: collaborator

Study Sites (10)

University of Calgary

Calgary, Alberta, T2V 1P9, Canada

RECRUITING

Links Clinic

Edmonton, Alberta, T5G 3G6, Canada

RECRUITING

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

RECRUITING

Grey Nuns Hospital

Edmonton, Alberta, T6L 5X8, Canada

RECRUITING

Lethbridge Regional Hospital

Lethbridge, Alberta, T1J 1W5, Canada

RECRUITING

Wetaskiwin Lung Laboratory

Wetaskiwin, Alberta, T9A 3B8, Canada

RECRUITING

Lion's Gate Hospital

North Vancouver, British Columbia, V7L 2N3, Canada

RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, V5Z 3J5, Canada

RECRUITING

St. Paul' Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

RECRUITING

Royal University Hospita

Saskatoon, Saskatchewan, S7N 0W8, Canada

RECRUITING

Related Publications (2)

• Sin DD, Man SF, Marciniuk DD, Ford G, FitzGerald M, Wong E, York E, Mainra RR, Ramesh W, Melenka LS, Wilde E, Cowie RL, Williams D, Rousseau R; ABC (Advair, Biomarkers in COPD) Investigators. Can inhaled fluticasone alone or in combination with salmeterol reduce systemic inflammation in chronic obstructive pulmonary disease? Study protocol for a randomized controlled trial [NCT00120978]. BMC Pulm Med. 2006 Feb 6;6:3. doi: 10.1186/1471-2466-6-3.

  PMID: 16460562 BACKGROUND

• Sin DD, Man SF, Marciniuk DD, Ford G, FitzGerald M, Wong E, York E, Mainra RR, Ramesh W, Melenka LS, Wilde E, Cowie RL, Williams D, Gan WQ, Rousseau R; ABC (Advair, Biomarkers in COPD) Investigators. The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008 Jun 1;177(11):1207-14. doi: 10.1164/rccm.200709-1356OC. Epub 2008 Feb 28.

  PMID: 18310480 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Fluticasone-Salmeterol Drug Combination; Fluticasone

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Don Sin, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roxanne Rousseau, BS

CONTACT

604-977-9791; RRousseau@mrl.ubc.ca

Don D Sin, MD

CONTACT

604-806-8395; dsin@mrl.ubc.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 11, 2005
• First Posted: July 19, 2005
• Study Start: December 1, 2004
• Study Completion: August 1, 2006
• Last Updated: May 9, 2006

Record last verified: 2005-04

Locations

CA (10)