Effect of QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) on Cardiac Function in COPD Patients

Phase 4

Completed

Conditions: Chronic Obstructive Pulmonary Disease, COPD

Interventions: Drug: QVA149
Drug: Placebo

Registration Number: NCT02442206

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This mechanistic study is a single-center, randomized, double-blind, placebo-controlled, cross-over study to evaluate the effect of dual bronchodilation with QVA149 on cardiac and lung function parameters in hyperinflated COPD patients.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 62

Inclusion Criteria

Patients with airflow limitation indicated by a post-bronchodilator FEV1 <80% of the predicted normal value and a post-bronchodilator FEV1/FVC<0.7
Current or ex-smokers who have a smoking history of at least 10 pack years.
Able and willing to give written informed consent
Hyperinflated patients with RVol>135% predicted

Exclusion Criteria

Patients on LABA or LAMA treatment at Visit 1.
History of one COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization 3 months prior to Visit 2.
More than one COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization within 6 months prior to Visit 2.
Patients who have clinically significant cardiovascular abnormalities, which could interfere with the assessment of the study treatment (such as but not limited to cardiac arrhythmias, heart failure with left ventricular ejection fraction <40% as determined by MRI scan, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, history of myocardial infarction 6 months prior to Visit 2)
Patients with a known history or current atrial fibrillation to be confirmed by ECG.
Patients with pacemaker, bypass or stent.
Patients whose QTcF measured at Visit 3 is >450 ms for males and >470 ms for females

Additional study-specific inclusion and exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment sequence 1	Placebo	QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
Treatment sequence 2	QVA149	Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
Treatment sequence 2	Placebo	Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
Treatment sequence 1	QVA149	QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43

Primary Outcome Measures

Name	Time	Method
Change in Left Ventricular End-diastolic Volume (LVEDV)	Baseline, week 2	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.

Secondary Outcome Measures

Name	Time	Method
Change in Left and Right Ventricular End-systolic Volume	Baseline, week 2	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.
Change in Forced Vital Capacity (FVC).	Baseline, week 2	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.
Change in Inspiratory Capacity (IC) at Each Time-point	Baseline, week 2	Inspiratory capacity (IC) was defined as the mean of the maximum IC over 3 values measured by bodyplethysmography according to internationally accepted standards.
Change in Functional Residual Capacity (FRC)	Baseline, week 2	Functional Residual Capacity (FRC) will be calculated as the mean of three reproducible values as measured by body plethymography according to internationally accepted standards.
Change in Forced Expiratory Volume in One Second (FEV1).	Baseline, week 2	Forced Expiratory Volume in one second (FEV1) will be calculated as the volume of air forcibly exhaled in one second as measured by spirometry.
Change in Residual Volume (RVol)	Baseline, week 2	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.
Change in Right Ventricular (RV) and Left Ventricular (LV) Ejection Fraction (EF)	Baseline, week 2	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.
Cardiac Output at Each Time-point, Left and Right Ventricular Cardiac Output (LVCO and RVCO)	week 2	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.
Change in Total Lung Capacity (TLC)	Baseline, week 2	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.
Change in Specific Airway Resistance (sRaw)	Baseline, week 2	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.
Change in Right Ventricular Enddiastolic Volume	Baseline, week 2	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.