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

• Status: Unknown status
• Trial end date: 2006-08-01
• Target enrollment: 0
• Participant gender: All

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. reduce CRP levels in stable COPD patients and

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)

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of British Columbia
• Collaborator: GlaxoSmithKline
• Treatments: Fluticasone; Fluticasone Propionate, Salmeterol Xinafoate Drug Combination

Criteria

Inclusion Criteria:

• 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