NCT01313676

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

Completed Phase 3 Results posted Last updated 6 August 2018

What this trial tests

Phase 3 trial testing fluticasone furoate/vilanterol in Pulmonary Disease, Chronic Obstructive in 16,568 participants. Completed in 15 July 2015.

Timeline

25 January 2011

Primary endpoint
15 July 2015

15 July 2015

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	16,568
Start date	25 January 2011
Primary completion	15 July 2015
Estimated completion	15 July 2015
Sites	1611 locations across Italy, Colombia, Japan, Malaysia, Taiwan, Vietnam, Poland, South Korea

Drugs / interventions tested

• fluticasone furoate/vilanterol
• fluticasone furoate (FLUTICASONE FUROATE) — full drug profile →
• vilanterol (VILANTEROL) — full drug profile →
• Placebo

Conditions studied

• Pulmonary Disease, Chronic Obstructive — all drugs for Pulmonary Disease, Chronic Obstructive →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 40 to 80, any sex, with Pulmonary Disease, Chronic Obstructive. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · From the date of randomization until date of death due to any cause (average of 2 study years)

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 low

Dead

Group	Value	95% CI
Placebo	275
Fluticasone Furoate 100 µg	251
Vilanterol 25 µg	265
Fluticasone Furoate/Vilanterol 100/25 µg	246

Alive

Group	Value	95% CI
Placebo	3832
Fluticasone Furoate 100 µg	3884
Vilanterol 25 µg	3853
Fluticasone Furoate/Vilanterol 100/25 µg	3874

Unknown

Group	Value	95% CI
Placebo	4
Fluticasone Furoate 100 µg	0
Vilanterol 25 µg	0
Fluticasone Furoate/Vilanterol 100/25 µg	1

Decline in Forced Expiratory Volume in 1 Second (FEV1) Secondary · From start date of IP until IP stop date + 1 (assessed up to 4 years)

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

Group	Value	95% CI
Placebo	-46	± 2.5
Fluticasone Furoate 100 µg	-38	± 2.4
Vilanterol 25 µg	-47	± 2.4
Fluticasone Furoate/Vilanterol 100/25 µg	-38	± 2.4

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

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 o

Had CV composite event

Group	Value	95% CI
Placebo	173
Fluticasone Furoate 100 µg	161
Vilanterol 25 µg	180
Fluticasone Furoate/Vilanterol 100/25 µg	174

No CV composite event

Group	Value	95% CI
Placebo	3938
Fluticasone Furoate 100 µg	3974
Vilanterol 25 µg	3938
Fluticasone Furoate/Vilanterol 100/25 µg	3947

Adverse events — posted to ClinicalTrials.gov

Time frame: 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).. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 918/4131 (22%)

Deaths: —

Fluticasone Furoate 100 µg

Serious: 929/4157 (22%)

Deaths: —

Vilanterol 25 µg

Serious: 972/4140 (23%)

Deaths: —

Fluticasone Furoate/Vilanterol 100/25 µg

Serious: 961/4140 (23%)

Deaths: —

Serious adverse events (1046 terms)

Reaction	System	Placebo	Fluticasone Furoate 100 µg	Vilanterol 25 µg	Fluticasone Furoate/Vilant…
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—	—
Angina unstable	Cardiac disorders	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—
Sudden death	General disorders	—	—	—	—
Ischaemic stroke	Nervous system disorders	—	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—	—
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Chest pain	General disorders	—	—	—	—
Transient ischaemic attack	Nervous system disorders	—	—	—	—
Peripheral arterial occlusive disease	Vascular disorders	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—	—
Cardio-respiratory arrest	Cardiac disorders	—	—	—	—
Limb traumatic amputation	Injury, poisoning and procedural complications	—	—	—	—

Other adverse events (10 terms — click to expand)

Reaction	System	Placebo	Fluticasone Furoate 100 µg	Vilanterol 25 µg	Fluticasone Furoate/Vilant…
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Dyspnoea	Nervous system disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Influenza	Infections and infestations	—	—	—	—

Most-reported serious reactions: Chronic obstructive pulmonary disease, Pneumonia, Atrial fibrillation, Myocardial infarction, Cardiac failure congestive, Acute myocardial infarction, Cardiac failure, Coronary artery disease.

Data from ClinicalTrials.gov NCT01313676 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial.
   Vestbo J, Anderson JA, Brook RD, Calverley PM, et al · · 2016 · cited 326× · PMID 27203508 · DOI 10.1016/s0140-6736(16)30069-1
2. Exacerbations of Chronic Obstructive Pulmonary Disease and Cardiac Events. A Post Hoc Cohort Analysis from the SUMMIT Randomized Clinical Trial.
   Kunisaki KM, Dransfield MT, Anderson JA, Brook RD, et al · · 2018 · cited 239× · PMID 29442524 · DOI 10.1164/rccm.201711-2239oc
3. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease.
   Kew KM, Seniukovich A. · · 2014 · cited 233× · PMID 24615270 · DOI 10.1002/14651858.cd010115.pub2
4. Blood Eosinophil Counts in Clinical Trials for Chronic Obstructive Pulmonary Disease.
   Singh D, Bafadhel M, Brightling CE, Sciurba FC, et al · · 2020 · cited 77× · PMID 32186896 · DOI 10.1164/rccm.201912-2384pp
5. FEV<sub>1</sub> is a stronger mortality predictor than FVC in patients with moderate COPD and with an increased risk for cardiovascular disease.
   Bikov A, Lange P, Anderson JA, Brook RD, et al · · 2020 · cited 51× · PMID 32547001 · DOI 10.2147/copd.s242809
6. Cardiac Troponin I and Cardiovascular Risk in Patients With Chronic Obstructive Pulmonary Disease.
   Adamson PD, Anderson JA, Brook RD, Calverley PMA, et al · · 2018 · cited 45× · PMID 30165984 · DOI 10.1016/j.jacc.2018.06.051
7. Fluticasone Furoate, Vilanterol, and Lung Function Decline in Patients with Moderate Chronic Obstructive Pulmonary Disease and Heightened Cardiovascular Risk.
   Calverley PMA, Anderson JA, Brook RD, Crim C, et al · · 2018 · cited 40× · PMID 28737971 · DOI 10.1164/rccm.201610-2086oc
8. Cardiovascular outcomes with an inhaled beta2-agonist/corticosteroid in patients with COPD at high cardiovascular risk.
   Brook RD, Anderson JA, Calverley PM, Celli BR, et al · · 2017 · cited 39× · PMID 28416587 · DOI 10.1136/heartjnl-2016-310897