Clinical trial NCT02442206: Effect of QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) on Cardiac Function in COPD Patients
Official title: A Randomized, Double-blinded, Single-center, Placebo Controlled, Cross-over Study to Assess the Effect of QVA149 (Indacaterol Maleate / Glycopyrronium Bromide) on Cardiac Function in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease, COPD
Keywords: QVA149, cardiac function, ventricular enddiastolic volume, hyperinflated COPD patients
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-05-13
Enrollment: 62
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Left Ventricular End-diastolic Volume (LVEDV)
timeFrame: Baseline, week 2
Secondary outcomes:
measure: Change in Forced Expiratory Volume in One Second (FEV1).
timeFrame: Baseline, week 2
measure: Change in Forced Vital Capacity (FVC).
timeFrame: Baseline, week 2
measure: Change in Inspiratory Capacity (IC) at Each Time-point
timeFrame: Baseline, week 2
measure: Change in Total Lung Capacity (TLC)
timeFrame: Baseline, week 2
measure: Change in Residual Volume (RVol)
timeFrame: Baseline, week 2
measure: Change in Specific Airway Resistance (sRaw)
timeFrame: Baseline, week 2
measure: Change in Functional Residual Capacity (FRC)
timeFrame: Baseline, week 2
measure: Change in Right Ventricular (RV) and Left Ventricular (LV) Ejection Fraction (EF)
timeFrame: Baseline, week 2
measure: Change in Left and Right Ventricular End-systolic Volume
timeFrame: Baseline, week 2
measure: Change in Right Ventricular Enddiastolic Volume
timeFrame: Baseline, week 2
measure: Cardiac Output at Each Time-point, Left and Right Ventricular Cardiac Output (LVCO and RVCO)
timeFrame: week 2
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Vogel-Claussen J, Schonfeld CO, Kaireit TF, Voskrebenzev A, Czerner CP, Renne J, Tillmann HC, Berschneider K, Hiltl S, Bauersachs J, Welte T, Hohlfeld JM. Effect of Indacaterol/Glycopyrronium on Pulmonary Perfusion and Ventilation in Hyperinflated Patients with Chronic Obstructive Pulmonary Disease (CLAIM). A Double-Blind, Randomized, Crossover Trial. Am J Respir Crit Care Med. 2019 May 1;199(9):1086-1096. doi: 10.1164/rccm.201805-0995OC.
citation: Hohlfeld JM, Vogel-Claussen J, Biller H, Berliner D, Berschneider K, Tillmann HC, Hiltl S, Bauersachs J, Welte T. Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial. Lancet Respir Med. 2018 May;6(5):368-378. doi: 10.1016/S2213-2600(18)30054-7. Epub 2018 Feb 21.