Study to Evaluate the Effect of Fluticasone Furoate/Vilanterol on Survival in Subjects With Chronic Obstructive Pulmonary Disease
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): fluticasone furoate/vilanterol; fluticasone furoate; vilanterol; Placebo
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): 100/25mcg given once daily via novel dry powder inhaler; 100mcg given once daily via novel dry powder inhaler; 25mcg given once daily via novel dry powder inhaler; placebo comparator once daily via novel dry powder inhaler
Intervention MeSH terms: Fluticasone; Xhance
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: COPD; Cardiovascular disease; Novel Dry Powder Inhaler; Survival