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CompletedNCT01313676Updated Aug 6, 2018Results posted

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

A Phase 3 interventional study of fluticasone furoate/vilanterol and fluticasone furoate in Pulmonary Disease, Chronic Obstructive, sponsored by GlaxoSmithKline. Completed at 1,621 sites in 44 countries. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2018-08-06.

Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
16,568
Allocation
Randomized
Ages
40 Years to 80 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Pulmonary Disease, Chronic Obstructive

Keywords

  • COPD
  • Cardiovascular disease
  • Novel Dry Powder Inhaler
  • Survival
03

In context

Lung Diseases

3,303 studies on the registry are indexed under Lung Diseases; 355 are open to participants now.

This study's enrollment of 16,568 is above the median of 72 across 2,118 interventional studies indexed under Lung Diseases.

Browse Lung Diseases studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
16,568 participants (actual)

Study arms

  • Experimental
    fluticasone furoate/vilanterol

    Combination of both products in one inhaler

    Drug: fluticasone furoate/vilanterol

  • Experimental
    fluticasone furoate

    comparator of individual component

    Drug: fluticasone furoate

  • Experimental
    vilanterol

    comparator of individual component

    Drug: vilanterol

  • Placebo comparator
    placebo

    once daily via inhaler

    Other: Placebo

Interventions

  • Drugfluticasone furoate/vilanterol

    100/25mcg given once daily via novel dry powder inhaler

  • Drugfluticasone furoate

    100mcg given once daily via novel dry powder inhaler

  • Drugvilanterol

    25mcg given once daily via novel dry powder inhaler

  • OtherPlacebo

    placebo comparator once daily via novel dry powder inhaler

06

What researchers measure

Primary outcomes

  1. Number of Participants With Death (Both on and Off Treatment) Due to Any Cause, Time up to or on the Pre-determined Common End Date

    Death from any cause: which occurred from the day of starting IP until the Commone End Date (CED). Common End Date (CED) is the study end date that was pre determined where approximately 1000 deaths would have occurred in the Intent-toTreat Efficacy (ITT-E) Population. Only deaths which occurred on or before the CED were used for the primary analysis. Those who had not died by CED, but who were known to be alive on or after the CED, were censored at the CED. Cox Proportional Hazards (PH) Model was adjusted for age, and gender, including all 4 arms. A hazard ratio of less than 1 indicates a lower death rate versus placebo or other arm. ITT-E Population consisted of all participants in the Safety Population (i.e. randomized to IP and who received at least one dose of IP), with the exception of those recruited at sites that were closed.

    Time frame: From the date of randomization until date of death due to any cause (average of 2 study years)

Secondary outcomes

  1. Decline in Forced Expiratory Volume in 1 Second (FEV1)

    FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The effect of treatment on decline of post bronchodilator FEV1 recorded during the treatment period was analyzed using a particular form of a mixed effect model - a random coefficients model. FEV1 was fitted as the response variable with treatment group, age, gender, baseline FEV1 and time on treatment as fixed effects. Time on treatment was treated as a continuous variable. This model allowed for an initial increase in FEV1, but then tested the difference in slopes from the first post-baseline measurement which was at 3 months. A negative slope indicates a decline. A positive treatment difference indicates a slower rate of decline vs Placebo or Component. Only participants with at least one on-treatment post-bronchodilator FEV1 measurement were analyzed.

    Time frame: From start date of IP until IP stop date + 1 (assessed up to 4 years)

  2. Number of Participants With First On-treatment Cardiovascular (CV) Composite Events Occured on or Before Common End Date

    On-treatment CV composite event is comprised of the first event that is adjudicated as on-treatment CV death, myocardial infarction, stroke, unstable angina, or transient ischemic attack experienced by a participant. The events that occurred no more than 7 days after the participants last dose of IP are considered as on-treatment adverse events. Common end date is the study end date where approximately 1000 deaths would have occurred in the ITT-E Population. Cox PH Model was used to assess time to first on-treatment CV composite event. Cox PH Model was adjusted for age, gender and indicators of ischemic and vascular disease, including all four treatment arms. A hazard ratio less than 1 indicates a lower risk of a first CV event rate versus placebo or any arm.

    Time frame: From the start of IP to first on treatment CV event till 7 days after the last dose of IP (average of 2 study years)

07

Results

Posted Aug 9, 2016

Participant flow

This study was conducted at 1373 sites. The study employed an event-driven design and was to conclude when approximately 1000 reports of a primary outcome event of death were received. The study consisted of a 4-10 day run-in period, variable treatment period until the required number of events was achieved, and 1 week follow-up period.

Participant flow — Overall Study
MilestonePlaceboFluticasone Furoate 100 µgVilanterol 25 µgFluticasone Furoate/Vilanterol 100/25 µg
Started4131415741404140
Completed2881304430523146
Not completed125011131088994
Withdrew: Adverse event395365372333
Withdrew: Lack of efficacy98906546
Withdrew: Protocol violation37444644
Withdrew: Met protocol-defined stopping critera34211
Withdrew: Study closed/terminated7699
Withdrew: Lost to follow-up0010
Withdrew: Physician decision53646248
Withdrew: Decision by participant or proxy643527515492
Withdrew: Sponsor terminated study treatment1101
Withdrew: Investigator site closed12111510
Withdrew: Missing1110

Outcome measures

PrimaryNumber of Participants With Death (Both on and Off Treatment) Due to Any Cause, Time up to or on the Pre-determined Common End Date

Death from any cause: which occurred from the day of starting IP until the Commone End Date (CED). Common End Date (CED) is the study end date that was pre determined where approximately 1000 deaths would have occurred in the Intent-toTreat Efficacy (ITT-E) Population. Only deaths which occurred on or before the CED were used for the primary analysis. Those who had not died by CED, but who were known to be alive on or after the CED, were censored at the CED. Cox Proportional Hazards (PH) Model was adjusted for age, and gender, including all 4 arms. A hazard ratio of less than 1 indicates a lower death rate versus placebo or other arm. ITT-E Population consisted of all participants in the Safety Population (i.e. randomized to IP and who received at least one dose of IP), with the exception of those recruited at sites that were closed.

Time frame:
From the date of randomization until date of death due to any cause (average of 2 study years)
Reported as:
Number · Participants
Number of Participants With Death (Both on and Off Treatment) Due to Any Cause, Time up to or on the Pre-determined Common End Date
ParticipantsPlaceboFluticasone Furoate 100 µgVilanterol 25 µgFluticasone Furoate/Vilanterol 100/25 µg
Dead275251265246
Alive3832388438533874
Unknown4001
Statistical analysis
  • Placebo vs Fluticasone Furoate/Vilanterol 100/25 µg · Cox Proportional Hazards Model · p = 0.137 · Hazard ratio (hr): 0.878 · 95% CI 0.739 to 1.042
  • Placebo vs Fluticasone Furoate/Vilanterol 100/25 µg · Percent reduction in risk of death: 12.2 · 95% CI -4.2 to 26.1Confidence Interval (95%) and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)\*100
  • Placebo vs Fluticasone Furoate 100 µg · Cox Proportional Hazards Model · p = 0.284 · Hazard ratio (hr): 0.911 · 95% CI 0.767 to 1.081
  • Placebo vs Fluticasone Furoate 100 µg · Percent reduction in risk of death: 8.9 · 95% CI -8.1 to 23.3Confidence Interval (95%) and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)\*100
  • Placebo vs Vilanterol 25 µg · Cox Proportional Hazards Model · p = 0.655 · Hazard ratio (hr): 0.962 · 95% CI 0.813 to 1.139
  • Placebo vs Vilanterol 25 µg · Percent reduction in risk of death: 3.8 · 95% CI -13.9 to 18.7Confidence Interval (95%) and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)\*100
  • Fluticasone Furoate 100 µg vs Fluticasone Furoate/Vilanterol 100/25 µg · Cox Proportional Hazards Model · p = 0.681 · Hazard ratio (hr): 0.964 · 95% CI 0.808 to 1.149
  • Fluticasone Furoate 100 µg vs Fluticasone Furoate/Vilanterol 100/25 µg · Percent reduction in risk of death: 3.6 · 95% CI -14.9 to 19.2Confidence Interval (95%) and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)\*100
  • Vilanterol 25 µg vs Fluticasone Furoate/Vilanterol 100/25 µg · Cox Proportional Hazards Model · p = 0.299 · Hazard ratio (hr): 0.912 · 95% CI 0.767 to 1.085
  • Vilanterol 25 µg vs Fluticasone Furoate/Vilanterol 100/25 µg · Percent reduction in risk of death: 8.8 · 95% CI -8.5 to 23.3Confidence Interval (95%) and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)\*100
SecondaryDecline in Forced Expiratory Volume in 1 Second (FEV1)

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The effect of treatment on decline of post bronchodilator FEV1 recorded during the treatment period was analyzed using a particular form of a mixed effect model - a random coefficients model. FEV1 was fitted as the response variable with treatment group, age, gender, baseline FEV1 and time on treatment as fixed effects. Time on treatment was treated as a continuous variable. This model allowed for an initial increase in FEV1, but then tested the difference in slopes from the first post-baseline measurement which was at 3 months. A negative slope indicates a decline. A positive treatment difference indicates a slower rate of decline vs Placebo or Component. Only participants with at least one on-treatment post-bronchodilator FEV1 measurement were analyzed.

Time frame:
From start date of IP until IP stop date + 1 (assessed up to 4 years)
Reported as:
Least squares mean · milliliter/year
Decline in Forced Expiratory Volume in 1 Second (FEV1)
milliliter/yearPlaceboFluticasone Furoate 100 µgVilanterol 25 µgFluticasone Furoate/Vilanterol 100/25 µg
Decline in Forced Expiratory Volume in 1 Second (FEV1)-46 ± 2.5-38 ± 2.4-47 ± 2.4-38 ± 2.4
Statistical analysis
  • Placebo vs Fluticasone Furoate/Vilanterol 100/25 µg · Mixed Models Analysis · p = 0.019 · Mean difference (final values): 8 · 95% CI 1 to 15
  • Placebo vs Fluticasone Furoate 100 µg · Mixed Models Analysis · p = 0.026 · Mean difference (final values): 8 · 95% CI 1 to 14
  • Placebo vs Vilanterol 25 µg · Mixed Models Analysis · p = 0.654 · Mean difference (final values): -2 · 95% CI -8 to 5
  • Fluticasone Furoate 100 µg vs Fluticasone Furoate/Vilanterol 100/25 µg · Mixed Models Analysis · p = 0.913 · Mean difference (final values): 0 · 95% CI -6 to 7
  • Vilanterol 25 µg vs Fluticasone Furoate/Vilanterol 100/25 µg · Mixed Models Analysis · p = 0.004 · Mean difference (final values): 10 · 95% CI 3 to 16
SecondaryNumber of Participants With First On-treatment Cardiovascular (CV) Composite Events Occured on or Before Common End Date

On-treatment CV composite event is comprised of the first event that is adjudicated as on-treatment CV death, myocardial infarction, stroke, unstable angina, or transient ischemic attack experienced by a participant. The events that occurred no more than 7 days after the participants last dose of IP are considered as on-treatment adverse events. Common end date is the study end date where approximately 1000 deaths would have occurred in the ITT-E Population. Cox PH Model was used to assess time to first on-treatment CV composite event. Cox PH Model was adjusted for age, gender and indicators of ischemic and vascular disease, including all four treatment arms. A hazard ratio less than 1 indicates a lower risk of a first CV event rate versus placebo or any arm.

Time frame:
From the start of IP to first on treatment CV event till 7 days after the last dose of IP (average of 2 study years)
Reported as:
Number · Participants
Number of Participants With First On-treatment Cardiovascular (CV) Composite Events Occured on or Before Common End Date
ParticipantsPlaceboFluticasone Furoate 100 µgVilanterol 25 µgFluticasone Furoate/Vilanterol 100/25 µg
Had CV composite event173161180174
No CV composite event3938397439383947
Statistical analysis
  • Placebo vs Fluticasone Furoate/Vilanterol 100/25 µg · Cox Proportional Hazards Model · p = 0.475 · Hazard ratio (hr): 0.926 · 95% CI 0.750 to 1.143
  • Placebo vs Fluticasone Furoate/Vilanterol 100/25 µg · Percent reduction in risk of cv event: 7.4 · 95% CI -14.3 to 25.0Confidence Interval and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)\*100
  • Placebo vs Fluticasone Furoate 100 µg · Cox Proportional Hazards Model · p = 0.317 · Hazard ratio (hr): 0.896 · 95% CI 0.723 to 1.111
  • Placebo vs Fluticasone Furoate 100 µg · Percent reduction in risk of cv event: 10.4 · 95% CI -11.1 to 27.7Confidence Interval and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)\*100
  • Placebo vs Vilanterol 25 µg · Cox Proportional Hazards Model · p = 0.908 · Hazard ratio (hr): 0.988 · 95% CI 0.802 to 1.217
  • Placebo vs Vilanterol 25 µg · Percent reduction in risk of death: 1.2 · 95% CI -21.7 to 19.8Confidence Interval and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)\*100
  • Fluticasone Furoate 100 µg vs Fluticasone Furoate/Vilanterol 100/25 µg · Cox Proportional Hazards Model · p = 0.763 · Hazard ratio (hr): 1.033 · 95% CI 0.834 to 1.281
  • Fluticasone Furoate 100 µg vs Fluticasone Furoate/Vilanterol 100/25 µg · Percent reduction in risk of death: -3.3 · 95% CI -28.1 to 16.6Confidence Interval and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)\*100
  • Vilanterol 25 µg vs Fluticasone Furoate/Vilanterol 100/25 µg · Cox Proportional Hazards Model · p = 0.545 · Hazard ratio (hr): 0.938 · 95% CI 0.761 to 1.155
  • Vilanterol 25 µg · Percent reduction in risk of death: 6.2 · 95% CI -15.5 to 23.9Confidence Interval and Estimated Value is presented for the percent reduction in risk of death at any time up to or on the CED, calculated as (1-hazard ratio)\*100

Adverse events

Collected over On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP until IP discontinuation + 1 day (average of 2 study years).. Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—918/4,131 (22.2%)1,862/4,131 (45.1%)
Fluticasone Furoate 100 µg—929/4,157 (22.3%)1,941/4,157 (46.7%)
Vilanterol 25 µg—972/4,140 (23.5%)1,827/4,140 (44.1%)
Fluticasone Furoate/Vilanterol 100/25 µg—961/4,140 (23.2%)1,761/4,140 (42.5%)
Most frequent serious events
Showing 10 of 1,046
Most frequent serious events
EventPlaceboFluticasone Furoate 100 µgVilanterol 25 µgFluticasone Furoate/Vilanterol 100/25 µg
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders262/4131214/4157245/4140189/4140
PneumoniaInfections and infestations113/4131121/415790/4140123/4140
Atrial fibrillationCardiac disorders31/413122/415730/414032/4140
Myocardial infarctionCardiac disorders24/413132/415726/414024/4140
Cardiac failure congestiveCardiac disorders26/413126/415721/414030/4140
Cardiac failureCardiac disorders28/413117/415719/414028/4140
Acute myocardial infarctionCardiac disorders23/413120/415721/414028/4140
Coronary artery diseaseCardiac disorders22/413114/415725/414024/4140
Angina unstableCardiac disorders23/413122/415716/414023/4140
Angina pectorisCardiac disorders22/413119/415720/414012/4140
Most frequent other events
Most frequent other events
EventPlaceboFluticasone Furoate 100 µgVilanterol 25 µgFluticasone Furoate/Vilanterol 100/25 µg
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders969/4131939/4157938/4140779/4140
NasopharyngitisInfections and infestations310/4131366/4157352/4140367/4140
HeadacheNervous system disorders308/4131332/4157327/4140291/4140
Upper respiratory tract infectionInfections and infestations194/4131240/4157212/4140262/4140
CoughRespiratory, thoracic and mediastinal disorders254/4131224/4157215/4140206/4140
DyspnoeaNervous system disorders172/4131185/4157132/4140125/4140
BronchitisInfections and infestations165/4131184/4157168/4140166/4140
Back painMusculoskeletal and connective tissue disorders140/4131168/4157162/4140173/4140
HypertensionVascular disorders129/4131138/4157124/4140152/4140
InfluenzaInfections and infestations118/4131116/4157122/4140137/4140

Baseline characteristics

Age, Continuous
Age, Continuous(Years)PlaceboFluticasone Furoate 100 µgVilanterol 25 µgFluticasone Furoate/Vilanterol 100/25 µgTotal
Mean65.2 ± 7.9065.0 ± 8.0265.2 ± 7.6865.3 ± 7.9765.2 ± 7.89
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboFluticasone Furoate 100 µgVilanterol 25 µgFluticasone Furoate/Vilanterol 100/25 µgTotal
Female10501098107110194238
Male308130593069312112330
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboFluticasone Furoate 100 µgVilanterol 25 µgFluticasone Furoate/Vilanterol 100/25 µgTotal
African American /African Heritage61626869260
American Indian or Alaskan Native954927
Asian - Central /South Asian Heritage64556257238
Asian - East Asian Heritage192193195192772
Asian - Japanese Heritage34363737144
Asian - Mixed Race10001
Asian - South East Asian Heritage3893993863941568
Native Hawaiian or Other Pacific Islander12025
White - Arabic/North African Heritage141371246
White - Mixed Race00011
White - White/Caucasian /European Heritage333433673353333713391
Mixed Race32252830115
08

Study locations

1,621 sites
  • GSK Investigational Site
    Andalusia, Alabama 36420, United States
  • GSK Investigational Site
    Athens, Alabama 35611, United States
  • GSK Investigational Site
    Birmingham, Alabama 35209, United States
  • GSK Investigational Site
    Birmingham, Alabama 35216, United States
  • GSK Investigational Site
    Birmingham, Alabama 35233, United States
  • GSK Investigational Site
    Birmingham, Alabama 35242, United States
  • GSK Investigational Site
    Huntsville, Alabama 35801, United States
  • GSK Investigational Site
    Huntsville, Alabama 35816, United States
  • GSK Investigational Site
    Mobile, Alabama 36604, United States
  • GSK Investigational Site
    Mobile, Alabama 36608, United States
  • GSK Investigational Site
    Montgomery, Alabama 36106, United States
  • GSK Investigational Site
    Montgomery, Alabama 36109, United States
  • GSK Investigational Site
    Muscle Shoals, Alabama 35662, United States
  • GSK Investigational Site
    Ozark, Alabama 36360, United States
  • GSK Investigational Site
    Pell City, Alabama 35128, United States
  • GSK Investigational Site
    Tuscumbia, Alabama 35674, United States
  • GSK Investigational Site
    Flagstaff, Arizona 86001, United States
  • GSK Investigational Site
    Glendale, Arizona 85306, United States
  • GSK Investigational Site
    Phoenix, Arizona 85018, United States
  • GSK Investigational Site
    Phoenix, Arizona 85032, United States
  • GSK Investigational Site
    Scottsdale, Arizona 85258, United States
  • GSK Investigational Site
    Sierra Vista, Arizona 85635, United States
  • GSK Investigational Site
    Tucson, Arizona 85710, United States
  • GSK Investigational Site
    Tucson, Arizona 85745, United States
  • GSK Investigational Site
    Fayetteville, Arkansas 72703, United States
  • GSK Investigational Site
    Jonesboro, Arkansas 72401, United States
  • GSK Investigational Site
    Anaheim, California 92801, United States
  • GSK Investigational Site
    Bakersfield, California 93301, United States
  • GSK Investigational Site
    Cerritos, California 90703, United States
  • GSK Investigational Site
    Encinitas, California 92024, United States
  • GSK Investigational Site
    Foothill Ranch, California 92610, United States
  • GSK Investigational Site
    Fountain Valley, California 92708, United States
  • GSK Investigational Site
    Garden Grove, California 92844, United States
  • GSK Investigational Site
    Gold River, California 95670, United States
  • GSK Investigational Site
    Huntington Beach, California 92647, United States
  • GSK Investigational Site
    Huntington Park, California 90255, United States
  • GSK Investigational Site
    Lakewood, California 90712, United States
  • GSK Investigational Site
    Lancaster, California 93534, United States
  • GSK Investigational Site
    Loma Linda, California 92357, United States
  • GSK Investigational Site
    Long Beach, California 90822, United States
  • GSK Investigational Site
    Los Angeles, California 90033, United States
  • GSK Investigational Site
    Los Angeles, California 90036, United States
  • GSK Investigational Site
    Los Angeles, California 90048, United States
  • GSK Investigational Site
    Los Angeles, California 90095, United States
  • GSK Investigational Site
    Mission Hills, California 91345, United States
  • GSK Investigational Site
    Mission Viejo, California 92691, United States
  • GSK Investigational Site
    Modesto, California 95350, United States
  • GSK Investigational Site
    Montclair, California 91763, United States
  • GSK Investigational Site
    Monterey Park, California 91754, United States
  • GSK Investigational Site
    Oxnard, California 93030-5841, United States
  • GSK Investigational Site
    Palo Alto, California 94304, United States
  • GSK Investigational Site
    Pasadena, California 91105, United States
  • GSK Investigational Site
    Pismo Beach, California 93449, United States
  • GSK Investigational Site
    Rancho Mirage, California 92270, United States
  • GSK Investigational Site
    Riverside, California 92506, United States
  • GSK Investigational Site
    Rolling Hills Estates, California 90274, United States
  • GSK Investigational Site
    Sacramento, California 95816, United States
  • GSK Investigational Site
    Sacramento, California 95817, United States
  • GSK Investigational Site
    Sacramento, California 95819, United States
  • GSK Investigational Site
    Sacramento, California 95821, United States
  • GSK Investigational Site
    San Diego, California 91910, United States
  • GSK Investigational Site
    San Diego, California 92103, United States
  • GSK Investigational Site
    San Diego, California 92108, United States
  • GSK Investigational Site
    San Diego, California 92111, United States
  • GSK Investigational Site
    San Diego, California 92117, United States
  • GSK Investigational Site
    San Diego, California 92120, United States
  • GSK Investigational Site
    San Gabriel, California 91776, United States
  • GSK Investigational Site
    San Jose, California 95116, United States
  • GSK Investigational Site
    San Marino, California 91108, United States
  • GSK Investigational Site
    Santa Monica, California 90404, United States
  • GSK Investigational Site
    Sepulveda, California 91343, United States
  • GSK Investigational Site
    Simi Valley, California 93065, United States
  • GSK Investigational Site
    Stockton, California 95207, United States
  • GSK Investigational Site
    Torrance, California 90502, United States
  • GSK Investigational Site
    Torrance, California 90505, United States
  • GSK Investigational Site
    Van Nuys, California 91405, United States
  • GSK Investigational Site
    Ventura, California 93003, United States
  • GSK Investigational Site
    West Covina, California 91790, United States
  • GSK Investigational Site
    Centennial, Colorado 80112, United States
  • GSK Investigational Site
    Colorado Springs, Colorado 80907, United States
  • GSK Investigational Site
    Colorado Springs, Colorado 80910, United States
  • GSK Investigational Site
    Denver, Colorado 80206, United States
  • GSK Investigational Site
    Fort Collins, Colorado 80528, United States
  • GSK Investigational Site
    Fort Collins, Colorado 80538, United States
  • GSK Investigational Site
    Wheat Ridge, Colorado 80033, United States
  • GSK Investigational Site
    Danbury, Connecticut 06810, United States
  • GSK Investigational Site
    Hartford, Connecticut 06105, United States
  • GSK Investigational Site
    Waterbury, Connecticut 06708, United States
  • GSK Investigational Site
    Washington, District of Columbia 20422, United States
  • GSK Investigational Site
    Altamonte Springs, Florida 32714, United States
  • GSK Investigational Site
    Aventura, Florida 33180, United States
  • GSK Investigational Site
    Bay Pines, Florida 33744, United States
  • GSK Investigational Site
    Boynton Beach, Florida 33435, United States
  • GSK Investigational Site
    Boynton Beach, Florida 33472, United States
  • GSK Investigational Site
    Brandon, Florida 33511, United States
  • GSK Investigational Site
    Celebration, Florida 34747, United States
  • GSK Investigational Site
    Clearwater, Florida 33755, United States
  • GSK Investigational Site
    Clearwater, Florida 33756, United States
  • GSK Investigational Site
    Clearwater, Florida 33759, United States
  • GSK Investigational Site
    Clearwater, Florida 33765-2616, United States

Showing the first 100 of 1,621 sites across 44 countries.

09

References and documents

Publications

  • Horne BD, Hegewald MJ, Crim C, Rea S, Bair TL, Blagev DP. The Summit Score Stratifies Mortality and Morbidity in Chronic Obstructive Pulmonary Disease. Int J Chron Obstruct Pulmon Dis. 2020 Jul 20;15:1741-1750. doi: 10.2147/COPD.S254437. eCollection 2020. PubMed 32764918 ↗
  • Wise RA, Anderson JA, Amarenco P, Cowans NJ, Crim C, Denvir MA, Gomez CR, Jones MP, Morris A, Niewoehner D, Yates JC. Adjudication of cardiovascular events in patients with chronic obstructive pulmonary disease: SUMMIT trial. Clin Trials. 2020 Aug;17(4):430-436. doi: 10.1177/1740774520920897. Epub 2020 May 22. PubMed 32441114 ↗
  • Celli BR, Anderson JA, Brook R, Calverley P, Cowans NJ, Crim C, Dixon I, Kim V, Martinez FJ, Morris A, Newby DE, Yates J, Vestbo J. Serum biomarkers and outcomes in patients with moderate COPD: a substudy of the randomised SUMMIT trial. BMJ Open Respir Res. 2019 May 4;6(1):e000431. doi: 10.1136/bmjresp-2019-000431. eCollection 2019. PubMed 31258919 ↗
  • Fawzy A, Anderson JA, Cowans NJ, Crim C, Wise R, Yates JC, Hansel NN. Association of platelet count with all-cause mortality and risk of cardiovascular and respiratory morbidity in stable COPD. Respir Res. 2019 May 8;20(1):86. doi: 10.1186/s12931-019-1059-1. PubMed 31068182 ↗
  • Vestbo J, Dransfield M, Anderson JA, Brook RD, Calverley PMA, Celli BR, Cowans NJ, Crim C, Martinez F, Newby DE, Yates J, Lange P. Impact of pre-enrolment medication use on clinical outcomes in SUMMIT. ERJ Open Res. 2019 Feb 25;5(1):00203-2018. doi: 10.1183/23120541.00203-2018. eCollection 2019 Feb. PubMed 30815468 ↗
  • Adamson PD, Anderson JA, Brook RD, Calverley PMA, Celli BR, Cowans NJ, Crim C, Dixon IJ, Martinez FJ, Newby DE, Vestbo J, Yates JC, Mills NL. Cardiac Troponin I and Cardiovascular Risk in Patients With Chronic Obstructive Pulmonary Disease. J Am Coll Cardiol. 2018 Sep 4;72(10):1126-1137. doi: 10.1016/j.jacc.2018.06.051. Erratum In: J Am Coll Cardiol. 2018 Oct 30;72(18):2282. doi: 10.1016/j.jacc.2018.09.031. PubMed 30165984 ↗
  • Kunisaki KM, Dransfield MT, Anderson JA, Brook RD, Calverley PMA, Celli BR, Crim C, Hartley BF, Martinez FJ, Newby DE, Pragman AA, Vestbo J, Yates JC, Niewoehner DE; SUMMIT Investigators. Exacerbations of Chronic Obstructive Pulmonary Disease and Cardiac Events. A Post Hoc Cohort Analysis from the SUMMIT Randomized Clinical Trial. Am J Respir Crit Care Med. 2018 Jul 1;198(1):51-57. doi: 10.1164/rccm.201711-2239OC. PubMed 29442524 ↗
  • Celli B, Anderson JA, Brook R, Calverley P, Crim C, Holmes AP, Martinez FJ, Newby DE, Yates J, Vestbo J; SUMMIT Investigators. Long-Acting beta-Agonist/Inhaled Corticosteroid in Patients with Chronic Obstructive Pulmonary Disease with Cardiovascular Disease or Risk: A Factorial Analysis of the SUMMIT Clinical Trial. Am J Respir Crit Care Med. 2018 Jun 15;197(12):1641-1644. doi: 10.1164/rccm.201710-2052LE. No abstract available. PubMed 29412688 ↗
  • Dransfield MT, McAllister DA, Anderson JA, Brook RD, Calverley PMA, Celli BR, Crim C, Gallot N, Martinez FJ, Scanlon PD, Yates J, Vestbo J, Newby DE; SUMMIT Investigators. beta-Blocker Therapy and Clinical Outcomes in Patients with Moderate Chronic Obstructive Pulmonary Disease and Heightened Cardiovascular Risk. An Observational Substudy of SUMMIT. Ann Am Thorac Soc. 2018 May;15(5):608-614. doi: 10.1513/AnnalsATS.201708-626OC. PubMed 29406772 ↗
  • Bhatt SP, Anderson JA, Brook RD, Calverley PMA, Celli BR, Cowans NJ, Crim C, Martinez FJ, Newby DE, Vestbo J, Yates JC, Dransfield MT. Cigarette smoking and response to inhaled corticosteroids in COPD. Eur Respir J. 2018 Jan 18;51(1):1701393. doi: 10.1183/13993003.01393-2017. Print 2018 Jan. No abstract available. PubMed 29348179 ↗
  • Crim C, Calverley PMA, Anderson JA, Holmes AP, Kilbride S, Martinez FJ, Brook RD, Newby DE, Yates JC, Celli BR, Vestbo J; SUMMIT investigators. Pneumonia risk with inhaled fluticasone furoate and vilanterol in COPD patients with moderate airflow limitation: The SUMMIT trial. Respir Med. 2017 Oct;131:27-34. doi: 10.1016/j.rmed.2017.07.060. Epub 2017 Aug 1. PubMed 28947039 ↗
  • Calverley PMA, Anderson JA, Brook RD, Crim C, Gallot N, Kilbride S, Martinez FJ, Yates J, Newby DE, Vestbo J, Wise R, Celli BR; SUMMIT (Study to Understand Mortality and Morbidity) Investigators. Fluticasone Furoate, Vilanterol, and Lung Function Decline in Patients with Moderate Chronic Obstructive Pulmonary Disease and Heightened Cardiovascular Risk. Am J Respir Crit Care Med. 2018 Jan 1;197(1):47-55. doi: 10.1164/rccm.201610-2086OC. PubMed 28737971 ↗
  • Brook RD, Anderson JA, Calverley PM, Celli BR, Crim C, Denvir MA, Magder S, Martinez FJ, Rajagopalan S, Vestbo J, Yates J, Newby DE; SUMMIT Investigators. Cardiovascular outcomes with an inhaled beta2-agonist/corticosteroid in patients with COPD at high cardiovascular risk. Heart. 2017 Oct;103(19):1536-1542. doi: 10.1136/heartjnl-2016-310897. Epub 2017 Apr 17. PubMed 28416587 ↗
  • Martinez FJ, Vestbo J, Anderson JA, Brook RD, Celli BR, Cowans NJ, Crim C, Dransfield M, Kilbride S, Yates J, Newby DE, Niewoehner D, Calverley PM; SUMMIT Investigators. Effect of Fluticasone Furoate and Vilanterol on Exacerbations of Chronic Obstructive Pulmonary Disease in Patients with Moderate Airflow Obstruction. Am J Respir Crit Care Med. 2017 Apr 1;195(7):881-888. doi: 10.1164/rccm.201607-1421OC. PubMed 27767328 ↗
  • Vestbo J, Anderson JA, Brook RD, Calverley PM, Celli BR, Crim C, Martinez F, Yates J, Newby DE; SUMMIT Investigators. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1817-26. doi: 10.1016/S0140-6736(16)30069-1. Epub 2016 Apr 28. PubMed 27203508 ↗
  • Vestbo J, Anderson J, Brook RD, Calverley PM, Celli BR, Crim C, Haumann B, Martinez FJ, Yates J, Newby DE. The Study to Understand Mortality and Morbidity in COPD (SUMMIT) study protocol. Eur Respir J. 2013 May;41(5):1017-22. doi: 10.1183/09031936.00087312. Epub 2012 Sep 27. PubMed 23018908 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 6, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01313676
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Mar 14, 2011
Start date
Jan 25, 2011
Primary completion
Jul 15, 2015
Completion
Jul 15, 2015
Results posted
Aug 9, 2016
Last update
Aug 6, 2018

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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