Study to Evaluate the 24-Hour Pulmonary Function Profile of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25mcg Once Daily Compared With Tiotropium Bromide Inhalation Powder 18mcg Once Daily in Subjects With COPD Who Have or Are At Risk for Co-morbid Cardiovascular Disease
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Respiratory Aspiration; Pulmonary Disease, Chronic Obstructive; Cardiovascular Diseases
Intervention: fluticasone furoate/vilanterol 100/25mcg; tiotropium bromide 18mcg
Intervention description: inhalation powder; inhalation powder
Intervention MeSH terms: Fluticasone; Xhance; Bromides; Tiotropium Bromide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 623.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Cardiovascular event; Cardiovascular disease

Summary:

      The purpose of this study is to evaluate the 24-hour spirometry effect (FEV1) of Fluticasone
      Furoate/Vilanterol Inhalation Powder 100/25mcg once daily compared with tiotropium bromide
      inhalation powder 18mcg once daily over a 12-week treatment period in subjects with COPD who
      have or are at risk for co-morbid cardiovascular disease
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed and dated written informed consent

          -  Male or females ≥ 40 years of age

          -  Females must be post-menopausal or using a highly effective method for avoidance of
             pregnancy

          -  Established clinical history of COPD by ATS/ERS definition

          -  Post-albuterol spirometry criteria: FEV1/FVC ratio ≤ 0.70 and FEV1 ≥30 to ≤ 70% of
             predicted normal (NHANES III)

          -  Former or current smoker ≥10 pack years

          -  A history of diagnosed cardiovascular disease or a prior cardiovascular event
             including any of the following:

          -  Established (i.e., by clinical signs or imaging studies) coronary artery disease (CAD)

          -  Established (i.e., by clinical signs or imaging studies) peripheral vascular (i.e.,
             arterial) disease (PVD)

          -  Previous stroke

          -  Objectively confirmed transient ischemic attack (TIA) (i.e., transient neurological
             deficit documented by a health-care professional)

          -  Previous myocardial infarction (MI) (Note: An MI within 6 months prior to Visit 1 is
             exclusionary)

        OR

          -  Presence of one of the following cardiovascular risk factors (in addition to being a
             former/current smoker):

          -  Current diagnosis of hypertension

          -  Current diagnosis of hypercholesterolemia

          -  Diabetes mellitus treated with pharmacotherapy

        Exclusion Criteria:

          -  Current diagnosis of asthma

          -  Subjects with other respiratory disorders including α1-antitrypsin deficiency as the
             underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis (Note:
             focal bronchiectasis is not exclusionary), sarcoidosis, pulmonary fibrosis (Note:
             focal fibrotic pulmonary lesions are not exclusionary), pulmonary hypertension,
             interstitial lung diseases or other active pulmonary diseases

          -  Lung volume reduction surgery within previous 12 months

          -  Clinically significant abnormalities not due to COPD by chest X-ray or CT scan

          -  Hospitalized for poorly controlled COPD within 12 weeks of Screening

          -  Poorly controlled COPD 6 weeks prior to Screening, defined as acute worsening of COPD
             that is managed by the subject with corticosteroids or antibiotics or that requires
             treatment prescribed by a physician

          -  Lower respiratory infection requiring antibiotics 6 weeks prior to Screening

          -  A moderate or severe COPD exacerbation and/or a lower respiratory tract infection
             (including pnuemonia) during the Run-In Period

          -  An abnormal, clinically significant finding in any liver chemistry, biochemical, or
             haematology tests at Screening (Visit 1) or upon repeat prior to randomization

          -  An abnormal, clinically significant ECG finding at Screening (Visit 1) or upon repeat
             prior to randomization

          -  An abnormal, clinically significant Holter finding at Screening (Visit 1) or upon
             repeat prior to randomization (sub-set of subjects)

          -  Historical or current evidence of clinically significant (in opinion of the
             Investigator) and unstable disease such as cardiovascular (e.g., patients requiring
             ICD, pacemaker requiring a ventricular pace rate set at >60 bpm, uncontrolled
             hypertension, New York Heart Association Class IV (New York Heart Association,1994),
             known left ventricular ejection fraction <30%), neurological, psychiatric, renal,
             hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid
             disease), peptic ulcer disease, or haematological abnormalities

          -  Carcinoma not in complete remission for at least 5 years

          -  History of allergy or hypersensitivity to any of the study medications (e.g.,
             anticholinergic/muscarinic receptor antagonist, beta2-agonist, corticosteroid) or
             components of the inhalation powder (e.g., lactose, magnesium stearate) or a medical
             condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck
             obstruction that, in the opinion of the study physician contraindicates study
             participation or use of an inhaled anticholinergic. In addition, subjects with a
             history of severe milk protein allergy that, in the opinion of the Investigator,
             contraindicates the subject's participation will also be excluded

          -  Known/suspected history of alcohol or drug abuse in the last 2 years

          -  Women who are pregnant or lactating or plan to become pregnant

          -  Subjects medically unable to withhold albuterol /salbutamol for 4 hours prior to
             spirometry testing at each study visit

          -  Use of certain medications such as bronchodilators and corticosteroids for the
             protocol-specific times prior to Visit 1 (the Investigator will discuss the specific
             medications)

          -  Long Term Oxygen Therapy (LTOT) or nocturnal oxygen therapy >12 hours a day

          -  Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks
             prior to Screening or during the study

          -  Failure to demonstrate adequate compliance defined as completion of the Diary Card
             (completed all diary entries on at least 4 of the last 7 consecutive days), the
             ability to withhold COPD medications and to keep clinic visit appointments

          -  Non-compliance or inability to comply with study procedures or scheduled visits

          -  History of psychiatric disease, intellectual deficiency, poor motivation or other
             conditions that will limit the validity of informed consent to participate in the
             study

          -  Affiliation with investigator site

          -  Women who are pregnant or lactating or are planning on becoming pregnant during the
             study