Clinical trial NCT01313676
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: COPD Cardiovascular disease Novel Dry Powder Inhaler Survival
Sponsor: GlaxoSmithKline
Start date: 2011-01-25; Completion date: 2015-07-15
Enrollment: 16568 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine if fluticasone furoate/vilanterol improves survival in patients with chronic obstructive pulmonary disease with a history of or increased risk of heart disease.

Detailed description:
Despite a potential link between the pathogenetic mechanisms involved in Chronic Obstructive Pulmonary Disease (COPD) and atherosclerotic cardiovascular disease, there are no currently approved therapies for patients with COPD that have clearly shown an additional beneficial effect in patients with cardiovascular comorbidities. The TOwards a Revolution in COPD Health (TORCH) study assessed the impact of the inhaled corticosteroid (ICS) fluticasone propionate (FP) in combination with the long-acting beta agonist (LABA), salmeterol (SAL), in reducing all-cause mortality. TORCH demonstrated a 17.5% reduction on all-cause mortality with salmeterol-fluticasone propionate combination (SFC) compared with placebo (HR=0.825, 95% CI (0.681, 1.002), p=0.052) in the entire COPD population with disease severity form moderate to very severe. A post hoc analysis of the data restricted to those subjects with an forced expiratory volume in 1 second (FEV1) \>=50% predicted with an apparent history of cardiovascular co-morbidities (defined as use at baseline of beta-blockers, angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), HMG CoA reductase inhibitors (i.e. statins) or a prior MI recorded at baseline) demonstrated a 49% reduction in the risk of dying within 96 weeks for the comparison of SFC with placebo. These post hoc data suggest the possibility of an ICS/LABA combination product to be of substantial benefit in COPD subjects with less severe airflow obstruction yet with increased cardiovascular risk.

The mechanism by which SFC appears to be associated with a greater reduction in mortality in these less severe COPD subjects with concomitant cardiovascular comorbidities is speculative at present, but could potentially in part be related to a lessening of the degree of inflammation in the systemic circulation, potential plaque stabilization and/or amelioration of arterial stiffness.

ICS/LABA combinations that are currently available require twice daily administration. A once daily ICS/LABA combination has the potential to improve patient compliance and as a result, overall disease management.

The purpose of this study is to prospectively evaluate the effect of the once daily ICS/LABA combination Fluticasone Furoate (FF)/Vilanterol (VI) on survival in subjects with moderate COPD (\>=50 and =\<70 % predicted FEV1 ) and a history of, or at increased risk for cardiovascular disease.

Arms: arm 1: Combination of both products in one inhaler arm 2: comparator of individual component arm 3: comparator of individual component arm 4: once daily via inhaler
Interventions: intervention 1: fluticasone furoate/vilanterol intervention 2: fluticasone furoate intervention 3: vilanterol intervention 4: Placebo
Intervention descriptions: intervention 1: 100/25mcg given once daily via novel dry powder inhaler intervention 2: 100mcg given once daily via novel dry powder inhaler intervention 3: 25mcg given once daily via novel dry powder inhaler intervention 4: placebo comparator once daily via novel dry powder inhaler

Protocol documents: