Trial Outcomes & Findings for Effect of QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) on Cardiac Function in COPD Patients (NCT NCT02442206)
NCT ID: NCT02442206
Last Updated: 2019-01-03
Results Overview
Left ventricular enddiastolic volume (LVEDV) is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the chamber's filling with blood and will be determined as measured by MRI.
COMPLETED
PHASE4
62 participants
Baseline, week 2
2019-01-03
Participant Flow
Participant milestones
| Measure |
Treatment Sequence 1
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Treatment Sequence 2
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Period 1
STARTED
|
30
|
32
|
|
Period 1
COMPLETED
|
29
|
29
|
|
Period 1
NOT COMPLETED
|
1
|
3
|
|
Period 2
STARTED
|
29
|
29
|
|
Period 2
COMPLETED
|
28
|
29
|
|
Period 2
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence 1
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Treatment Sequence 2
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Period 1
Adverse Event
|
1
|
1
|
|
Period 1
withdrew consent
|
0
|
1
|
|
Period 1
COPD exacerbation
|
0
|
1
|
|
Period 2
Adverse Event
|
1
|
0
|
Baseline Characteristics
Effect of QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) on Cardiac Function in COPD Patients
Baseline characteristics by cohort
| Measure |
Treatment Sequence 1
n=30 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Treatment Sequence 2
n=32 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.1 Years
STANDARD_DEVIATION 8.00 • n=99 Participants
|
63.8 Years
STANDARD_DEVIATION 7.80 • n=107 Participants
|
63.9 Years
STANDARD_DEVIATION 7.83 • n=206 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
45 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
30 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
62 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid LV EDV value at both baseline and post-baseline in a period were included
Left ventricular enddiastolic volume (LVEDV) is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the chamber's filling with blood and will be determined as measured by MRI.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Left Ventricular End-diastolic Volume (LVEDV)
|
11.873 ML
Standard Deviation 14.3215
|
-0.954 ML
Standard Deviation 12.2463
|
SECONDARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Forced Expiratory Volume in one second (FEV1) will be calculated as the volume of air forcibly exhaled in one second as measured by spirometry.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Forced Expiratory Volume in One Second (FEV1).
|
0.42 Liter
Standard Deviation 0.211
|
-0.01 Liter
Standard Deviation 0.168
|
SECONDARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC will be assessed via spirometry.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Forced Vital Capacity (FVC).
|
0.67 Liter
Standard Deviation 0.434
|
0.00 Liter
Standard Deviation 0.293
|
SECONDARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Inspiratory capacity (IC) was defined as the mean of the maximum IC over 3 values measured by bodyplethysmography according to internationally accepted standards.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Inspiratory Capacity (IC) at Each Time-point
|
0.475 Liters
Standard Deviation 0.3284
|
0.014 Liters
Standard Deviation 0.2388
|
SECONDARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Total Lung Capacity (TLC) will be calculated from the mean Functional Residual Capacity (FRC) plus the highest value of the Inspiratory Capacity, both measured by body plethymography according to internationally accepted standards.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Total Lung Capacity (TLC)
|
-0.181 Liters
Standard Deviation 0.3408
|
-0.001 Liters
Standard Deviation 0.3618
|
SECONDARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Residual Volume (RVol) will be calculated from the value of Total Lung Capacity (TLC) minus the highest value of the Slow Vital Capacity, both measured by body plethymography according to internationally accepted standards.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Residual Volume (RVol)
|
-0.757 Liters
Standard Deviation 0.5833
|
0.012 Liters
Standard Deviation 0.5141
|
SECONDARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Specific Airway Resistance (sRaw) will be documented as effective resistance (sReff) calculated as the median of five acceptable measurements. Values will be measured by body plethymography according to internationally accepted standards.
Outcome measures
| Measure |
QVA149
n=56 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=55 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Specific Airway Resistance (sRaw)
|
-1.887 kPa*s/L
Standard Deviation 1.0979
|
0.037 kPa*s/L
Standard Deviation 1.0383
|
SECONDARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Functional Residual Capacity (FRC) will be calculated as the mean of three reproducible values as measured by body plethymography according to internationally accepted standards.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Functional Residual Capacity (FRC)
|
-0.656 Liters
Standard Deviation 0.4602
|
-0.015 Liters
Standard Deviation 0.4257
|
SECONDARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Right and left ventricular ejection fraction is the fraction of blood (in percent) pumped out of the heart's left and right ventricular chamber, respectively, with each heart beat and will be determined as measured by MRI.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Right Ventricular (RV) and Left Ventricular (LV) Ejection Fraction (EF)
LV-EF
|
1.893 Percentage
Standard Deviation 5.8486
|
1.313 Percentage
Standard Deviation 5.4261
|
|
Change in Right Ventricular (RV) and Left Ventricular (LV) Ejection Fraction (EF)
RV-EF
|
2.046 Percentage
Standard Deviation 5.8746
|
0.361 Percentage
Standard Deviation 6.1936
|
SECONDARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Right ventricular end-systolic volume (RV-ESV) and left ventricular end-systolic volume (LV-ESV) is a measurement of the volume of blood in the heart's right and left ventricular chamber, respectively, at the end of the heart's contraction and will be determined as measured by MRI.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Left and Right Ventricular End-systolic Volume
LV-ESV
|
1.898 ML
Standard Deviation 8.4565
|
-2.283 ML
Standard Deviation 8.1489
|
|
Change in Left and Right Ventricular End-systolic Volume
RV-ESV
|
2.183 ML
Standard Deviation 8.7063
|
0.133 ML
Standard Deviation 9.3370
|
SECONDARY outcome
Timeframe: Baseline, week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Right ventricular end-diastolic volume is a measurement of the volume of blood in the heart's right ventricular chamber at the end of the chamber's filling with blood and will be determined as measured by MRI.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Change in Right Ventricular Enddiastolic Volume
|
12.323 ML
Standard Deviation 13.9683
|
1.758 ML
Standard Deviation 14.7904
|
SECONDARY outcome
Timeframe: week 2Population: Per protocol set (PPS) included all patients in the FAS who did not have any major protocol deviations. Only patients with a valid value for parameter at both baseline and post-baseline in a period are included - Period baseline was defined as the value taken in each period prior to start of study treatment
Cardiac output is calculated as the heart rate multiplied by the stroke volume (= difference between ventricular enddiastolic volume and endsystolic volume) that will be determined as measured by MRI.
Outcome measures
| Measure |
QVA149
n=57 Participants
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
|
Placebo
n=59 Participants
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
|
|---|---|---|
|
Cardiac Output at Each Time-point, Left and Right Ventricular Cardiac Output (LVCO and RVCO)
LVCO
|
0.504 Liter/min
Standard Deviation 0.7919
|
0.119 Liter/min
Standard Deviation 0.8970
|
|
Cardiac Output at Each Time-point, Left and Right Ventricular Cardiac Output (LVCO and RVCO)
RVCO
|
0.517 Liter/min
Standard Deviation 0.8063
|
0.144 Liter/min
Standard Deviation 0.9523
|
Adverse Events
QVA149 (110/50)
Placebo
All Patients
Serious adverse events
| Measure |
QVA149 (110/50)
n=59 participants at risk
QVA149 (110/50)
|
Placebo
n=61 participants at risk
Placebo
|
All Patients
n=62 participants at risk
All Patients
|
|---|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/59 • For the study duration of about 13 weeks
|
1.6%
1/61 • For the study duration of about 13 weeks
|
1.6%
1/62 • For the study duration of about 13 weeks
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/59 • For the study duration of about 13 weeks
|
1.6%
1/61 • For the study duration of about 13 weeks
|
1.6%
1/62 • For the study duration of about 13 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
1.7%
1/59 • For the study duration of about 13 weeks
|
0.00%
0/61 • For the study duration of about 13 weeks
|
1.6%
1/62 • For the study duration of about 13 weeks
|
Other adverse events
| Measure |
QVA149 (110/50)
n=59 participants at risk
QVA149 (110/50)
|
Placebo
n=61 participants at risk
Placebo
|
All Patients
n=62 participants at risk
All Patients
|
|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
5.1%
3/59 • For the study duration of about 13 weeks
|
4.9%
3/61 • For the study duration of about 13 weeks
|
9.7%
6/62 • For the study duration of about 13 weeks
|
|
Infections and infestations
Nasopharyngitis
|
5.1%
3/59 • For the study duration of about 13 weeks
|
1.6%
1/61 • For the study duration of about 13 weeks
|
6.5%
4/62 • For the study duration of about 13 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
8.5%
5/59 • For the study duration of about 13 weeks
|
6.6%
4/61 • For the study duration of about 13 weeks
|
14.5%
9/62 • For the study duration of about 13 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.1%
3/59 • For the study duration of about 13 weeks
|
1.6%
1/61 • For the study duration of about 13 weeks
|
6.5%
4/62 • For the study duration of about 13 weeks
|
|
Nervous system disorders
Headache
|
6.8%
4/59 • For the study duration of about 13 weeks
|
8.2%
5/61 • For the study duration of about 13 weeks
|
11.3%
7/62 • For the study duration of about 13 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.3%
9/59 • For the study duration of about 13 weeks
|
1.6%
1/61 • For the study duration of about 13 weeks
|
16.1%
10/62 • For the study duration of about 13 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.4%
2/59 • For the study duration of about 13 weeks
|
3.3%
2/61 • For the study duration of about 13 weeks
|
6.5%
4/62 • For the study duration of about 13 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
11.9%
7/59 • For the study duration of about 13 weeks
|
4.9%
3/61 • For the study duration of about 13 weeks
|
16.1%
10/62 • For the study duration of about 13 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER