Study to Evaluate the Effect of Fluticasone Furoate/Vilanterol on Survival in Subjects With Chronic Obstructive Pulmonary Disease



Status:Completed
Conditions:Chronic Obstructive Pulmonary Disease, Peripheral Vascular Disease, Pulmonary
Therapuetic Areas:Cardiology / Vascular Diseases, Pulmonary / Respiratory Diseases
Healthy:No
Age Range:40 - 80
Updated:8/8/2018
Start Date:January 25, 2011
End Date:July 15, 2015

Use our guide to learn which trials are right for you!

A Clinical Outcomes Study to Compare the Effect of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg With Placebo on Survival in Subjects With Moderate Chronic Obstructive Pulmonary Disease (COPD) and a History of or at Increased Risk for Cardiovascular Disease

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.

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.

Inclusion Criteria:

- Type of subject: outpatient.

- Informed consent: Subjects must give their signed and dated written informed consent
to participate.

- Gender: Male or female. Female subjects must be post-menopausal or using a highly
effective method for avoidance of pregnancy. The decision to include or exclude women
of childbearing potential may be made at the discretion of the investigator in
accordance with local practice in relation to adequate contraception.

- Age: >=40 and <=80 years of age at Screening (Visit 1).

- Tobacco use: Subjects with a current or prior history of >=10 pack-years of cigarette
smoking at screening (Visit 1). Previous smokers are defined as those who have stopped
smoking for at least 6 months prior to Visit 1.

- Airflow Obstruction:

Subjects with a measured post-albuterol/salbutamol forced expiratory volume in 1 second
(FEV1)/(forced vital capacity)FVC ratio of <=0.70 at Screening (Visit 1).

Subjects with a measured post-albuterol/salbutamol FEV1 >=50 and <=70% of predicted normal
values calculated using NHANES III reference equations [Hankinson, 1999; Hankinson, 2010]
at Screening (Visit 1).

Post-bronchodilator spirometry will be performed approximately 15 minutes after the subject
has self-administered 4 inhalations (i.e., total 400mcg) of albuterol/salbutamol via a
metered dose inhaler (MDI )with a valved-holding chamber. The FEV1/FVC ratio and FEV1
percent predicted values will be calculated.

- Symptoms of COPD: Subjects must score 2 or higher on the modified Medical Research
Council Dyspnea scale (Visit 1)

- Cardiovascular disease:

For patients >= 40 years of age: any one 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 disease (PVD)
Previous stroke Previous MI Diabetes mellitus with target organ disease OR

For patients >=60 years of age: any 2 of the following:

Being treated for hypercholesterolemia Being treated for hypertension Being treated for
diabetes mellitus Being treated for peripheral vascular disease

Exclusion Criteria:

- Pregnancy: Women who are pregnant or lactating.

- Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of
asthma are eligible if they also have a current diagnosis of COPD).

- alpha 1-antitrypsin deficiency: Subjects with known alpha-1 antitrypsin deficiency as
the underlying cause of COPD.

- Other respiratory disorders: Subjects with active tuberculosis, lung cancer,
bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial
lung diseases or other active pulmonary diseases.

- Lung resection or transplantation: Subjects with lung volume reduction surgery within
the 12 months prior to Screening or having had a lung transplant.

- A moderate/severe COPD exacerbation that has not resolved at least 14 days prior to
Visit 1 and at least 30 days following the last dose of oral corticosteroids (if
applicable).

- Current severe heart failure (New York Heart Association class IV). Subjects will also
be excluded if they have a known ejection fraction of <30% or if they have an
implantable cardioverter defibrillator (ICD).

- Other diseases/abnormalities: Any life-threatening condition with life expectancy <3
years, other than vascular disease or COPD, that might prevent the subject from
completing the study.

- End stage chronic renal disease: Subjects will be excluded if on renal replacement
therapy (hemodialysis or peritoneal).

- Drug/food allergy: Subjects with a history of hypersensitivity to any of the study
medications (e.g. beta-agonists, corticosteroid) or components of the inhalation
powder (e.g. lactose, magnesium stearate). In addition, patients with a history of
severe milk protein allergy that, in the opinion of the study physician,
contraindicates the subject's participation will also be excluded.

- Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug
abuse within the last 2 years.

- Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or
nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use
(i.e. <=12 hours per day) is not exclusionary.

- Questionable validity of consent: Subjects with a history of psychiatric disease,
intellectual deficiency, poor motivation or other conditions that will limit the
validity of informed consent to participate in the study or the potential compliance
to study procedures.

- Affiliation with investigator site: Study investigators, sub-investigators, study
coordinators, employees of a participating investigator or immediate family members of
the aforementioned are excluded from participating in this study.

- Additional medication: Use of the following medications within the following time
intervals prior to Visit 1 or during the study (unless otherwise specified):

Medication No use within the following time intervals prior to Screening or thereafter at
any time during the study (unless otherwise specified) Inhaled Long acting beta-agonists
(LABA) 48 hours ICS/LABA combination products 48 hours Inhaled corticosteroids 48 hours
Tiotropium 1 week Systemic, Oral, parenteral, intra-articular corticosteroids 30 days (oral
and systemic corticosteroids may be used to treat COPD exacerbations during the study)
Cytochrome P450 3A4 strong inhibitors including but not limited to antiretrovirals
(protease inhibitors) (e.g.Indinavir, Nelfinavir, Ritonavir, Saquinavir); Imidazole and
Triazole anti-fungals (e.g. Ketaconazole, Itraconazole); Clarithromycin, Telithromycin,
Amiodarone, and Nefazodone 6 weeks Grapefruit is allowed up to Visit 1, then limited to no
more than one glass of grapefruit juice (250 mL/ 8 ounces) or one grapefruit per day Any
other investigational drug 30 days or 5 half lives whichever is longer.
We found this trial at
521
sites
Huntsville, Alabama 35801
?
mi
from
Huntsville, AL
Click here to add this to my saved trials
Abingdon, Virginia 24210
?
mi
from
Abingdon, VA
Click here to add this to my saved trials
Adrogue, Buenos Aires
?
mi
from
Adrogue,
Click here to add this to my saved trials
Akron, Ohio 44313
?
mi
from
Akron, OH
Click here to add this to my saved trials
Albany, New York 12206
?
mi
from
Albany, NY
Click here to add this to my saved trials
Albuquerque, New Mexico 87109
?
mi
from
Albuquerque, NM
Click here to add this to my saved trials
Alexandria, Virginia 22304
?
mi
from
Alexandria, VA
Click here to add this to my saved trials
Altamonte Springs, Florida 32714
?
mi
from
Altamonte Springs, FL
Click here to add this to my saved trials
Amarillo, Texas 79106
?
mi
from
Amarillo, TX
Click here to add this to my saved trials
Anaheim, California 92807
?
mi
from
Anaheim, CA
Click here to add this to my saved trials
Anaheim, California 92807
?
mi
from
Anaheim, CA
Click here to add this to my saved trials
Andalusia, Alabama 36420
?
mi
from
Andalusia, AL
Click here to add this to my saved trials
Anderson, South Carolina 29621
?
mi
from
Anderson, SC
Click here to add this to my saved trials
Ann Arbor, Michigan 48109
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
Asheville, North Carolina 28803
?
mi
from
Asheville, NC
Click here to add this to my saved trials
Athens, Alabama 35611
?
mi
from
Athens, AL
Click here to add this to my saved trials
Atlanta, Georgia 30341
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
Auburn, Maine 04210
?
mi
from
Auburn, ME
Click here to add this to my saved trials
Aurora, Illinois 60504
?
mi
from
Aurora, IL
Click here to add this to my saved trials
Austell, Georgia 30106
?
mi
from
Austell, GA
Click here to add this to my saved trials
Austin, Texas 78705
?
mi
from
Austin, TX
Click here to add this to my saved trials
Austin, Texas 78705
?
mi
from
Austin, TX
Click here to add this to my saved trials
Austin, Texas 78705
?
mi
from
Austin, TX
Click here to add this to my saved trials
Aventura, Florida 33180
?
mi
from
Aventura, FL
Click here to add this to my saved trials
Avon, Indiana 46123
?
mi
from
Avon, IN
Click here to add this to my saved trials
Bakersfield, California 93309
?
mi
from
Bakersfield, CA
Click here to add this to my saved trials
Baltimore, Maryland 21201
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
Baltimore, Maryland 21201
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
Baltimore, Maryland 21201
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
Bangor, Maine 04401
?
mi
from
Bangor, ME
Click here to add this to my saved trials
Bangor, Maine 04401
?
mi
from
Bangor, ME
Click here to add this to my saved trials
Bay Pines, Florida 33744
?
mi
from
Bay Pines, FL
Click here to add this to my saved trials
Beaver, Pennsylvania 15009
?
mi
from
Beaver, PA
Click here to add this to my saved trials
Belle Vernon, Pennsylvania 15012
?
mi
from
Belle Vernon, PA
Click here to add this to my saved trials
Bellevue, Nebraska 68123
?
mi
from
Bellevue, NE
Click here to add this to my saved trials
Bellingham, Washington 98225
?
mi
from
Bellingham, WA
Click here to add this to my saved trials
Bend, Oregon 97701
?
mi
from
Bend, OR
Click here to add this to my saved trials
Bend, Oregon 97701
?
mi
from
Bend, OR
Click here to add this to my saved trials
Bensalem, Pennsylvania 19020
?
mi
from
Bensalem, PA
Click here to add this to my saved trials
Biddeford, Maine 04005
?
mi
from
Biddeford, ME
Click here to add this to my saved trials
Billings, Montana 59102
?
mi
from
Billings, MT
Click here to add this to my saved trials
Billings, Montana 59102
?
mi
from
Billings, MT
Click here to add this to my saved trials
Birmingham, Alabama 35249
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
Birmingham, Alabama 35249
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
Birmingham, Alabama 35249
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
Birmingham, Alabama 35249
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
Birmingham, Alabama 35249
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
Blue Ridge, Georgia 30513
?
mi
from
Blue Ridge, GA
Click here to add this to my saved trials
Boerne, Texas 78006
?
mi
from
Boerne, TX
Click here to add this to my saved trials
Boise, Idaho 83712
?
mi
from
Boise, ID
Click here to add this to my saved trials
Bowling Green, Kentucky 42101
?
mi
from
Bowling Green, KY
Click here to add this to my saved trials
Boynton Beach, Florida 33472
?
mi
from
Boynton Beach, FL
Click here to add this to my saved trials
Boynton Beach, Florida 33472
?
mi
from
Boynton Beach, FL
Click here to add this to my saved trials
Brandon, Florida 33511
?
mi
from
Brandon, FL
Click here to add this to my saved trials
Brandon, Florida 33511
?
mi
from
Brandon, FL
Click here to add this to my saved trials
Brick, New Jersey 08723
?
mi
from
Brick, NJ
Click here to add this to my saved trials
Bridgeport, West Virginia 26330
?
mi
from
Bridgeport, WV
Click here to add this to my saved trials
Brockton, Massachusetts 02301
?
mi
from
Brockton, MA
Click here to add this to my saved trials
Bronx, New York 10461
?
mi
from
Bronx, NY
Click here to add this to my saved trials
Bronxville, New York 10708
?
mi
from
Bronxville, NY
Click here to add this to my saved trials
Brooklyn, New York 11215
?
mi
from
Brooklyn, NY
Click here to add this to my saved trials
Brooklyn, New York 11215
?
mi
from
Brooklyn, NY
Click here to add this to my saved trials
Buckley, Michigan 49620
?
mi
from
Buckley, MI
Click here to add this to my saved trials
Buffalo, New York 14263
?
mi
from
Buffalo, NY
Click here to add this to my saved trials
Burien, Washington 98166
?
mi
from
Burien, WA
Click here to add this to my saved trials
Burke, Virginia 22015
?
mi
from
Burke, VA
Click here to add this to my saved trials
Butte, Montana 59701
?
mi
from
Butte, MT
Click here to add this to my saved trials
Cadillac, Michigan 49601
?
mi
from
Cadillac, MI
Click here to add this to my saved trials
Calabash, North Carolina 28467
?
mi
from
Calabash, NC
Click here to add this to my saved trials
Calhoun, Georgia 30701
?
mi
from
Calhoun, GA
Click here to add this to my saved trials
Canton, Georgia 30114
?
mi
from
Canton, GA
Click here to add this to my saved trials
Celebration, Florida 34747
?
mi
from
Celebration, FL
Click here to add this to my saved trials
Centennial, Colorado 80112
?
mi
from
Centennial, CO
Click here to add this to my saved trials
Cerritos, California 90703
?
mi
from
Cerritos, CA
Click here to add this to my saved trials
Champaign, Illinois 61820
?
mi
from
Champaign, IL
Click here to add this to my saved trials
Chardon, Ohio 44024
?
mi
from
Chardon, OH
Click here to add this to my saved trials
Charleston, South Carolina 29425
?
mi
from
Charleston, SC
Click here to add this to my saved trials
Charleston, South Carolina 29425
?
mi
from
Charleston, SC
Click here to add this to my saved trials
Charlotte, North Carolina 28203
?
mi
from
Charlotte, NC
Click here to add this to my saved trials
Charlotte, North Carolina 28203
?
mi
from
Charlotte, NC
Click here to add this to my saved trials
Charlotte, North Carolina 28203
?
mi
from
Charlotte, NC
Click here to add this to my saved trials
Chattanooga, Tennessee 37421
?
mi
from
Chattanooga, TN
Click here to add this to my saved trials
Chesterfield, Missouri 63017
?
mi
from
Chesterfield, MO
Click here to add this to my saved trials
Chicago, Illinois 60611
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Chicago, Illinois 60611
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Cincinnati, Ohio 45229
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
Cincinnati, Ohio 45229
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
Cincinnati, Ohio 45229
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
Clairton, Pennsylvania 15025
?
mi
from
Clairton, PA
Click here to add this to my saved trials
Clearwater, Florida 33759
?
mi
from
Clearwater, FL
Click here to add this to my saved trials
Clearwater, Florida 33759
?
mi
from
Clearwater, FL
Click here to add this to my saved trials
Clearwater, Florida 33759
?
mi
from
Clearwater, FL
Click here to add this to my saved trials
Clearwater, Florida 33759
?
mi
from
Clearwater, FL
Click here to add this to my saved trials
Clearwater, Florida 33759
?
mi
from
Clearwater, FL
Click here to add this to my saved trials
Cleveland, Ohio 44195
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
Cleveland, Ohio 44195
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
Cleveland, Ohio 44195
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
Coeur d'Alene, Idaho 83814
?
mi
from
Coeur d'Alene, ID
Click here to add this to my saved trials
Coeur d'Alene, Idaho 83814
?
mi
from
Coeur d'Alene, ID
Click here to add this to my saved trials
Colorado Springs, Colorado 80910
?
mi
from
Colorado Springs, CO
Click here to add this to my saved trials
Colorado Springs, Colorado 80910
?
mi
from
Colorado Springs, CO
Click here to add this to my saved trials