Trial Outcomes & Findings for A Study to Compare the Impact of Fulticasone Furoate/Vilanterol vs. Tiotropium on Arterial Stiffness in COPD (NCT NCT01395888)
NCT ID: NCT01395888
Last Updated: 2018-02-15
Results Overview
PWV is defined as the speed of travel of the pressure pulse along an arterial segment and can be obtained for any arterial segment accessible to palpation. aPWV is measured with tonometers positioned transcutaneously at the base of the common carotid artery and over the femoral artery. PWV increases with arterial stiffness and is defined by the Moens-Korteweg equation: PWV=square root of Eh/2pR, where E is Young's modulus of the arterial wall, h is the wall thickness, R is the arterial radius at the end of diastole, and p is the blood density. Change from Baseline was calculated as the Day 84 value minus the Baseline value. The analysis was performed using a repeated measures model with covariates of treatment, visit, age, gender, smoking status at screening, geographical region, Baseline aPWV, and interaction terms of Baseline by visit and treatment by visit.
COMPLETED
PHASE3
260 participants
Baseline to Day 84 (Early Withdrawal)
2018-02-15
Participant Flow
A total of 260 participants were randomized. Three of these participants were randomized in error (they were determined not to have met entry criteria and were classified as run-in/screen failures); thus, they did not receive investigational product and are not captured in the Treatment Period table of the Participant Flow module.
At Visit (V) 1, eligible participants (par.) entered a 2-week, single-blind placebo Run-in Period (RIP) to establish a stable baseline. At V 2, eligible par. were randomized to a 12-week, double-blind, double-dummy Treatment Period. 802 par. were screened, 279 par. entered the RIP, and 257 par. were randomized and received \>=1 study treatment dose.
Participant milestones
| Measure |
Salb/Alb + IBr
Participants were provided with an inhaled short-acting beta2-receptor agonist, salbutamol/albuterol (Salb/Alb), for use as needed throughout the Run-in Period for relief of chronic obstructive pulmonary disease (COPD) symptoms. Ipratropium bromide (IBr) was permitted during the Run-in Period and for up to 4 hours prior to Randomization (Visit 2) if the participant was on a stable dose prior to Screening (Visit 1). Following randomization, IBr was not permitted during exposure to study treatment.
|
FF/VI 100/25 µg
Participants (par.) self-administered one inhalation of Fluticasone Furoate /Vilanterol (FF/VI) 100/25 micrograms (µg) via a dry powder inhaler (DPI) followed by 2 inhalations from a single placebo capsule delivered via a HandiHaler in the morning for 12 weeks. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of Chronic Obstructive Pulmonary Disease (COPD) symptoms.
|
Tiotropium Bromide 18 µg
Participants self-administered one inhalation of placebo via an DPI followed by 2 inhalations from a single capsule containing Tiotropiuum Bromide 18 µg via a HandiHaler. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of COPD symptoms.
|
|---|---|---|---|
|
2-week Run-in Period
STARTED
|
279
|
0
|
0
|
|
2-week Run-in Period
COMPLETED
|
257
|
0
|
0
|
|
2-week Run-in Period
NOT COMPLETED
|
22
|
0
|
0
|
|
Treatment Period (TP)
STARTED
|
0
|
127
|
130
|
|
Treatment Period (TP)
Completed the Treatment Period
|
0
|
112
|
113
|
|
Treatment Period (TP)
COMPLETED
|
0
|
112
|
113
|
|
Treatment Period (TP)
NOT COMPLETED
|
0
|
15
|
17
|
Reasons for withdrawal
| Measure |
Salb/Alb + IBr
Participants were provided with an inhaled short-acting beta2-receptor agonist, salbutamol/albuterol (Salb/Alb), for use as needed throughout the Run-in Period for relief of chronic obstructive pulmonary disease (COPD) symptoms. Ipratropium bromide (IBr) was permitted during the Run-in Period and for up to 4 hours prior to Randomization (Visit 2) if the participant was on a stable dose prior to Screening (Visit 1). Following randomization, IBr was not permitted during exposure to study treatment.
|
FF/VI 100/25 µg
Participants (par.) self-administered one inhalation of Fluticasone Furoate /Vilanterol (FF/VI) 100/25 micrograms (µg) via a dry powder inhaler (DPI) followed by 2 inhalations from a single placebo capsule delivered via a HandiHaler in the morning for 12 weeks. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of Chronic Obstructive Pulmonary Disease (COPD) symptoms.
|
Tiotropium Bromide 18 µg
Participants self-administered one inhalation of placebo via an DPI followed by 2 inhalations from a single capsule containing Tiotropiuum Bromide 18 µg via a HandiHaler. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of COPD symptoms.
|
|---|---|---|---|
|
2-week Run-in Period
Adverse Event
|
2
|
0
|
0
|
|
2-week Run-in Period
Continuation Criteria Not Met
|
13
|
0
|
0
|
|
2-week Run-in Period
Lost to Follow-up
|
1
|
0
|
0
|
|
2-week Run-in Period
Protocol Violation
|
2
|
0
|
0
|
|
2-week Run-in Period
Withdrawal by Subject
|
4
|
0
|
0
|
|
Treatment Period (TP)
Adverse Event
|
0
|
7
|
6
|
|
Treatment Period (TP)
Lack of Efficacy
|
0
|
4
|
3
|
|
Treatment Period (TP)
Protocol Violation
|
0
|
1
|
5
|
|
Treatment Period (TP)
Met Protocol-defined Stopping Criteria
|
0
|
1
|
0
|
|
Treatment Period (TP)
Withdrawal by Subject
|
0
|
2
|
3
|
Baseline Characteristics
A Study to Compare the Impact of Fulticasone Furoate/Vilanterol vs. Tiotropium on Arterial Stiffness in COPD
Baseline characteristics by cohort
| Measure |
FF/VI 100/25 µg
n=127 Participants
Participants self-administered one inhalation of Fluticasone Furoate /Vilanterol (FF/VI) 100/25 micrograms (µg) via a dry powder inhaler (DPI) followed by 2 inhalations from a single placebo capsule delivered via a HandiHaler in the morning for 12 weeks. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of Chronic Obstructive Pulmonary Disease (COPD) symptoms.
|
Tiotropium Bromide 18 µg
n=130 Participants
Participants self-administered one inhalation of placebo via an DPI followed by 2 inhalations from a single capsule containing Tiotropiuum Bromide 18 µg via a HandiHaler. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of COPD symptoms.
|
Total
n=257 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66.7 Years
STANDARD_DEVIATION 7.20 • n=5 Participants
|
67.7 Years
STANDARD_DEVIATION 7.34 • n=7 Participants
|
67.3 Years
STANDARD_DEVIATION 7.28 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
108 Participants
n=5 Participants
|
112 Participants
n=7 Participants
|
220 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European
|
127 participants
n=5 Participants
|
130 participants
n=7 Participants
|
257 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Day 84 (Early Withdrawal)Population: Intent-to-Treat (ITT) Population: all participants (par.) who were randomized to and received \>=1 dose of randomized medication in the TP. The analysis model included all par. in the ITT Population without missing covariate information (MCI) and with \>=1 post-BL measurement. Par. presented represent those with data available at Day 84 without MCI.
PWV is defined as the speed of travel of the pressure pulse along an arterial segment and can be obtained for any arterial segment accessible to palpation. aPWV is measured with tonometers positioned transcutaneously at the base of the common carotid artery and over the femoral artery. PWV increases with arterial stiffness and is defined by the Moens-Korteweg equation: PWV=square root of Eh/2pR, where E is Young's modulus of the arterial wall, h is the wall thickness, R is the arterial radius at the end of diastole, and p is the blood density. Change from Baseline was calculated as the Day 84 value minus the Baseline value. The analysis was performed using a repeated measures model with covariates of treatment, visit, age, gender, smoking status at screening, geographical region, Baseline aPWV, and interaction terms of Baseline by visit and treatment by visit.
Outcome measures
| Measure |
FF/VI 100/25 µg
n=106 Participants
Participants self-administered one inhalation of Fluticasone Furoate /Vilanterol (FF/VI) 100/25 micrograms (µg) via a dry powder inhaler (DPI) followed by 2 inhalations from a single placebo capsule delivered via a HandiHaler in the morning for 12 weeks. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of Chronic Obstructive Pulmonary Disease (COPD) symptoms.
|
Tiotropium Bromide 18 µg
n=102 Participants
Participants self-administered one inhalation of placebo via an DPI followed by 2 inhalations from a single capsule containing Tiotropiuum Bromide 18 µg via a HandiHaler. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of COPD symptoms.
|
|---|---|---|
|
Mean Change From Baseline (BL) in Aortic Pulse Wave Velocity (aPWV) at the End of the 12-week Treatment Period (Day 84)
|
-0.859 meters per second (m/sec)
Standard Error 0.2590
|
-1.118 meters per second (m/sec)
Standard Error 0.2620
|
Adverse Events
FF/VI 100/25 µg
Tiotropium Bromide 18 µg
Serious adverse events
| Measure |
FF/VI 100/25 µg
n=127 participants at risk
Participants self-administered one inhalation of Fluticasone Furoate /Vilanterol (FF/VI) 100/25 micrograms (µg) via a dry powder inhaler (DPI) followed by 2 inhalations from a single placebo capsule delivered via a HandiHaler in the morning for 12 weeks. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of Chronic Obstructive Pulmonary Disease (COPD) symptoms.
|
Tiotropium Bromide 18 µg
n=130 participants at risk
Participants self-administered one inhalation of placebo via an DPI followed by 2 inhalations from a single capsule containing Tiotropiuum Bromide 18 µg via a HandiHaler. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of COPD symptoms.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.6%
2/127
|
3.8%
5/130
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/127
|
0.77%
1/130
|
|
Infections and infestations
Pneumonia
|
1.6%
2/127
|
0.00%
0/130
|
|
Infections and infestations
Peritonsillar abscess
|
0.00%
0/127
|
0.77%
1/130
|
|
Gastrointestinal disorders
Acute abdomen
|
0.79%
1/127
|
0.00%
0/130
|
|
Gastrointestinal disorders
Pancreatolithiasis
|
0.79%
1/127
|
0.00%
0/130
|
|
General disorders
Pyrexia
|
0.79%
1/127
|
0.00%
0/130
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.79%
1/127
|
0.00%
0/130
|
|
Injury, poisoning and procedural complications
Multiple injuries
|
0.00%
0/127
|
0.77%
1/130
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma
|
0.79%
1/127
|
0.00%
0/130
|
|
Nervous system disorders
Altered state of consciousness
|
0.79%
1/127
|
0.00%
0/130
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/127
|
0.77%
1/130
|
Other adverse events
| Measure |
FF/VI 100/25 µg
n=127 participants at risk
Participants self-administered one inhalation of Fluticasone Furoate /Vilanterol (FF/VI) 100/25 micrograms (µg) via a dry powder inhaler (DPI) followed by 2 inhalations from a single placebo capsule delivered via a HandiHaler in the morning for 12 weeks. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of Chronic Obstructive Pulmonary Disease (COPD) symptoms.
|
Tiotropium Bromide 18 µg
n=130 participants at risk
Participants self-administered one inhalation of placebo via an DPI followed by 2 inhalations from a single capsule containing Tiotropiuum Bromide 18 µg via a HandiHaler. An inhaled short-acting beta2-receptor agonist, salbutamol/albuterol, was provided for participants to use as needed throughout the Treatment Period for relief of COPD symptoms.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
3.9%
5/127
|
3.1%
4/130
|
|
Nervous system disorders
Headache
|
2.4%
3/127
|
3.8%
5/130
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER