Trial Outcomes & Findings for A 16-Week Study to Evaluate the Effect of Advair DISKUS™ 250/50mcg on Arterial Stiffness in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00857766)
NCT ID: NCT00857766
Last Updated: 2017-01-30
Results Overview
The 12-week Endpoint is defined as the last scheduled measurement of PWV during the 12-week double-blind treatment period (from Visits 3-5; Weeks 4, 8, and 12, respectively), and Baseline is defined as the PWV measure from Visit 2 (Randomization). Change from Baseline was calculated as the Endpoint value minus the Baseline Value. PWV is used as a measure of arterial stiffness, which is a measure of the cushioning functioning of major vessels like the aorta. The velocity of the PW along an artery is dependent on the stiffness of that artery.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
249 participants
Primary outcome timeframe
Baseline and the 12-Week Endpoint (up to Week 12)
Results posted on
2017-01-30
Participant Flow
Participant milestones
| Measure |
FSC DISKUS 250/50 mcg
Fluticasone Propionate/Salmeterol (FSC) DISKUS 250/50 micrograms (mcg) twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
Matching Placebo
Matching placebo DISKUS twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
|---|---|---|
|
Overall Study
STARTED
|
123
|
126
|
|
Overall Study
COMPLETED
|
92
|
96
|
|
Overall Study
NOT COMPLETED
|
31
|
30
|
Reasons for withdrawal
| Measure |
FSC DISKUS 250/50 mcg
Fluticasone Propionate/Salmeterol (FSC) DISKUS 250/50 micrograms (mcg) twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
Matching Placebo
Matching placebo DISKUS twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
|---|---|---|
|
Overall Study
Adverse Event
|
13
|
12
|
|
Overall Study
Protocol Violation
|
11
|
11
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Investigator Discretion
|
2
|
3
|
|
Overall Study
Participant Withdrew Consent
|
4
|
4
|
Baseline Characteristics
A 16-Week Study to Evaluate the Effect of Advair DISKUS™ 250/50mcg on Arterial Stiffness in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
FSC DISKUS 250/50 mcg
n=123 Participants
Fluticasone Propionate/Salmeterol (FSC) DISKUS 250/50 micrograms (mcg) twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
Matching Placebo
n=126 Participants
Matching placebo DISKUS twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
Total
n=249 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.6 Years
STANDARD_DEVIATION 8.92 • n=5 Participants
|
63.5 Years
STANDARD_DEVIATION 7.88 • n=7 Participants
|
63.5 Years
STANDARD_DEVIATION 8.40 • n=5 Participants
|
|
Gender
Female
|
55 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
|
Gender
Male
|
68 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
7 participants
n=5 Participants
|
9 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
114 participants
n=5 Participants
|
114 participants
n=7 Participants
|
228 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and the 12-Week Endpoint (up to Week 12)Population: Intent-to-Treat (ITT) Population: all participants who were randomized to study drug. The number analyzed at baseline is different from that at the 12-week endpoint due to participant withdrawal. Data are missing for some participants in the ITT Population.
The 12-week Endpoint is defined as the last scheduled measurement of PWV during the 12-week double-blind treatment period (from Visits 3-5; Weeks 4, 8, and 12, respectively), and Baseline is defined as the PWV measure from Visit 2 (Randomization). Change from Baseline was calculated as the Endpoint value minus the Baseline Value. PWV is used as a measure of arterial stiffness, which is a measure of the cushioning functioning of major vessels like the aorta. The velocity of the PW along an artery is dependent on the stiffness of that artery.
Outcome measures
| Measure |
FSC DISKUS 250/50 mcg
n=118 Participants
Fluticasone Propionate/Salmeterol (FSC) DISKUS 250/50 micrograms (mcg) twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
Matching Placebo
n=122 Participants
Matching placebo DISKUS twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
|---|---|---|
|
Mean Change From Baseline in Aortic Pulse Wave Velocity (aPWV) at the 12-Week Endpoint
Baseline, n=118, 122
|
10.06 meters per second (m/s)
Standard Error 0.26
|
9.87 meters per second (m/s)
Standard Error 0.25
|
|
Mean Change From Baseline in Aortic Pulse Wave Velocity (aPWV) at the 12-Week Endpoint
12-Week Endpoint, n=113, 110
|
9.83 meters per second (m/s)
Standard Error 0.24
|
9.95 meters per second (m/s)
Standard Error 0.26
|
|
Mean Change From Baseline in Aortic Pulse Wave Velocity (aPWV) at the 12-Week Endpoint
Change from Baseline
|
-0.24 meters per second (m/s)
Standard Error 0.194
|
0.13 meters per second (m/s)
Standard Error 0.157
|
SECONDARY outcome
Timeframe: Baseline and the 12-Week Endpoint (up to Week 12)Population: ITT Population. The number analyzed at baseline is different from that at the 12-week endpoint due to participant withdrawal. Data are missing for some participants in the ITT Population.
AIx is a surrogate measure of peripheral (not aortic) arterial resistance and is measured by analysis of the pulse wave at the radial artery. AIx = (\[delta P/Pulse Pressure\] x 100); delta P is defined by a notch near the peak of the pulse wave. Change from Baseline was calculated as the Endpoint value minus the Baseline Value.
Outcome measures
| Measure |
FSC DISKUS 250/50 mcg
n=121 Participants
Fluticasone Propionate/Salmeterol (FSC) DISKUS 250/50 micrograms (mcg) twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
Matching Placebo
n=122 Participants
Matching placebo DISKUS twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
|---|---|---|
|
Mean Change From Baseline in Augmentation Index (AIx) at the 12-Week Endpoint
Baseline, n=121, 122
|
27.9 % of total height of peak pulse pressure
Standard Error 0.83
|
27.8 % of total height of peak pulse pressure
Standard Error 0.83
|
|
Mean Change From Baseline in Augmentation Index (AIx) at the 12-Week Endpoint
12-Week Endpoint, n=114, 111
|
27.2 % of total height of peak pulse pressure
Standard Error 0.82
|
27.6 % of total height of peak pulse pressure
Standard Error 0.82
|
|
Mean Change From Baseline in Augmentation Index (AIx) at the 12-Week Endpoint
Change from Baseline
|
-0.7 % of total height of peak pulse pressure
Standard Error 0.66
|
-0.4 % of total height of peak pulse pressure
Standard Error 0.72
|
SECONDARY outcome
Timeframe: Baseline and the 12-Week Endpoint (up to Week 12)Population: ITT Population. The number analyzed at baseline is different from that at the 12-week endpoint due to participant withdrawal. Data are missing for some participants in the ITT Population.
FEV1 is a measure of air flow via spirometry. Change from Baseline was calculated as the Endpoint value minus the Baseline Value.
Outcome measures
| Measure |
FSC DISKUS 250/50 mcg
n=123 Participants
Fluticasone Propionate/Salmeterol (FSC) DISKUS 250/50 micrograms (mcg) twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
Matching Placebo
n=125 Participants
Matching placebo DISKUS twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
|---|---|---|
|
Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at the 12-Week Endpoint
Baseline, n=123, 125
|
1444 milliliters
Standard Error 53.7
|
1480 milliliters
Standard Error 60.1
|
|
Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at the 12-Week Endpoint
12-Week Endpoint, n=105, 102
|
1588 milliliters
Standard Error 59.6
|
1500 milliliters
Standard Error 61.6
|
|
Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at the 12-Week Endpoint
Change from Baseline
|
136 milliliters
Standard Error 22.0
|
-3 milliliters
Standard Error 30.4
|
Adverse Events
FSC DISKUS 250/50 mcg
Serious events: 8 serious events
Other events: 9 other events
Deaths: 0 deaths
Matching Placebo
Serious events: 8 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
FSC DISKUS 250/50 mcg
n=123 participants at risk
Fluticasone Propionate/Salmeterol (FSC) DISKUS 250/50 micrograms (mcg) twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
Matching Placebo
n=126 participants at risk
Matching placebo DISKUS twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.6%
2/123 • 16 week observation
|
2.4%
3/126 • 16 week observation
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.81%
1/123 • 16 week observation
|
0.00%
0/126 • 16 week observation
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.81%
1/123 • 16 week observation
|
0.00%
0/126 • 16 week observation
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/123 • 16 week observation
|
0.79%
1/126 • 16 week observation
|
|
Cardiac disorders
Acute myocardial infarction
|
0.81%
1/123 • 16 week observation
|
0.00%
0/126 • 16 week observation
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/123 • 16 week observation
|
0.79%
1/126 • 16 week observation
|
|
Infections and infestations
Pneumonia
|
2.4%
3/123 • 16 week observation
|
0.00%
0/126 • 16 week observation
|
|
Infections and infestations
Bronchitis
|
0.81%
1/123 • 16 week observation
|
0.00%
0/126 • 16 week observation
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma
|
0.00%
0/123 • 16 week observation
|
0.79%
1/126 • 16 week observation
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to spine
|
0.00%
0/123 • 16 week observation
|
0.79%
1/126 • 16 week observation
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/123 • 16 week observation
|
0.79%
1/126 • 16 week observation
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/123 • 16 week observation
|
0.79%
1/126 • 16 week observation
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.81%
1/123 • 16 week observation
|
0.00%
0/126 • 16 week observation
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/123 • 16 week observation
|
0.79%
1/126 • 16 week observation
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/123 • 16 week observation
|
0.79%
1/126 • 16 week observation
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.81%
1/123 • 16 week observation
|
0.00%
0/126 • 16 week observation
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm
|
0.81%
1/123 • 16 week observation
|
0.00%
0/126 • 16 week observation
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/123 • 16 week observation
|
0.79%
1/126 • 16 week observation
|
Other adverse events
| Measure |
FSC DISKUS 250/50 mcg
n=123 participants at risk
Fluticasone Propionate/Salmeterol (FSC) DISKUS 250/50 micrograms (mcg) twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
Matching Placebo
n=126 participants at risk
Matching placebo DISKUS twice daily. At Visit 5 (Week 12), participants received open-label Tiotropium inhalation capsules 18 mcg per dose via Handihaler inhalation device.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.5%
8/123 • 16 week observation
|
0.79%
1/126 • 16 week observation
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.81%
1/123 • 16 week observation
|
4.8%
6/126 • 16 week observation
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
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