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

Primary Purpose

Chronic Obstructive Pulmonary Disease, COPD

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
QVA149
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease, COPD focused on measuring QVA149, cardiac function, ventricular enddiastolic volume, hyperinflated COPD patients

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Treatment sequence 1

Treatment sequence 2

Arm Description

QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43

Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43

Outcomes

Primary Outcome Measures

Change in Left Ventricular End-diastolic Volume (LVEDV)
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

Change in Forced Expiratory Volume in One Second (FEV1).
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 Forced Vital Capacity (FVC).
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
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 Total Lung Capacity (TLC)
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 Residual Volume (RVol)
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 Specific Airway Resistance (sRaw)
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 Functional Residual Capacity (FRC)
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 Right Ventricular (RV) and Left Ventricular (LV) Ejection Fraction (EF)
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.
Change in Left and Right Ventricular End-systolic Volume
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 Right Ventricular Enddiastolic Volume
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.
Cardiac Output at Each Time-point, Left and Right Ventricular Cardiac Output (LVCO and RVCO)
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.

Full Information

First Posted
May 6, 2015
Last Updated
December 10, 2018
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02442206
Brief Title
Effect of QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) on Cardiac Function in COPD Patients
Acronym
CLAIM
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

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
May 18, 2015 (Actual)
Primary Completion Date
April 20, 2017 (Actual)
Study Completion Date
May 15, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease, COPD
Keywords
QVA149, cardiac function, ventricular enddiastolic volume, hyperinflated COPD patients

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
62 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment sequence 1
Arm Type
Experimental
Arm Description
QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
Arm Title
Treatment sequence 2
Arm Type
Experimental
Arm Description
Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43
Intervention Type
Drug
Intervention Name(s)
QVA149
Other Intervention Name(s)
Ultibro
Intervention Description
QVA149 capsules 100/50 µg for inhalation via Concept-1-inhaler, taken once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to QVA140 capsules 100/50 µg for inhalation via Concept-1-inhaler, taken once daily
Primary Outcome Measure Information:
Title
Change in Left Ventricular End-diastolic Volume (LVEDV)
Description
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.
Time Frame
Baseline, week 2
Secondary Outcome Measure Information:
Title
Change in Forced Expiratory Volume in One Second (FEV1).
Description
Forced Expiratory Volume in one second (FEV1) will be calculated as the volume of air forcibly exhaled in one second as measured by spirometry.
Time Frame
Baseline, week 2
Title
Change in Forced Vital Capacity (FVC).
Description
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.
Time Frame
Baseline, week 2
Title
Change in Inspiratory Capacity (IC) at Each Time-point
Description
Inspiratory capacity (IC) was defined as the mean of the maximum IC over 3 values measured by bodyplethysmography according to internationally accepted standards.
Time Frame
Baseline, week 2
Title
Change in Total Lung Capacity (TLC)
Description
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.
Time Frame
Baseline, week 2
Title
Change in Residual Volume (RVol)
Description
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.
Time Frame
Baseline, week 2
Title
Change in Specific Airway Resistance (sRaw)
Description
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.
Time Frame
Baseline, week 2
Title
Change in Functional Residual Capacity (FRC)
Description
Functional Residual Capacity (FRC) will be calculated as the mean of three reproducible values as measured by body plethymography according to internationally accepted standards.
Time Frame
Baseline, week 2
Title
Change in Right Ventricular (RV) and Left Ventricular (LV) Ejection Fraction (EF)
Description
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.
Time Frame
Baseline, week 2
Title
Change in Left and Right Ventricular End-systolic Volume
Description
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.
Time Frame
Baseline, week 2
Title
Change in Right Ventricular Enddiastolic Volume
Description
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.
Time Frame
Baseline, week 2
Title
Cardiac Output at Each Time-point, Left and Right Ventricular Cardiac Output (LVCO and RVCO)
Description
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.
Time Frame
week 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
30641027
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.
Results Reference
derived
PubMed Identifier
29477448
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.
Results Reference
derived

Learn more about this trial

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

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