Chronic Obstructive Pulmonary Disease, COPDPhase 4CLAIMNCT02442206

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

A Phase 4 study testing QVA149 in people with Chronic Obstructive Pulmonary Disease, COPD, run by Novartis Pharmaceuticals at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: Chronic Obstructive Pulmonary Disease, COPD
What is being tested?: QVA149
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 62 participants
Where: 1 siteGermany
Study dates: 18 May 2015to 15 May 2017
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Germany1 site

Novartis Investigative Site
Hanover, 30625

Other trials in Germany

About this study

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)

Conditions: Chronic Obstructive Pulmonary Disease, COPD
Being tested: QVA149, Placebo
Keywords: QVA149, cardiac function, ventricular enddiastolic volume, hyperinflated COPD patients
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

QVA149Drug
Also called Ultibro
QVA149 capsules 100/50 µg for inhalation via Concept-1-inhaler, taken once daily
PlaceboDrug
Placebo to QVA140 capsules 100/50 µg for inhalation via Concept-1-inhaler, taken once daily

Study groups in NCT02442206
Study group	Role	What they receive
Treatment sequence 1	Experimental	QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43 Receives: Drug: QVA149; Drug: Placebo
Treatment sequence 2	Experimental	Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43 Receives: Drug: QVA149; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, week 2

Secondary outcomes (11)

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.
Measured: Baseline, week 2
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.
Measured: Baseline, week 2
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.
Measured: Baseline, week 2
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.
Measured: Baseline, week 2
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.
Measured: Baseline, week 2
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.
Measured: Baseline, week 2
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.
Measured: Baseline, week 2
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.
Measured: Baseline, week 2
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.
Measured: Baseline, week 2
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.
Measured: Baseline, week 2
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.
Measured: week 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 May 201515 May 2017

First posted13 May 2015 (estimated)
Study start18 May 2015
Primary completion20 Apr 2017
Study completion15 May 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Chronic Obstructive Pulmonary Disease, COPDStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 62 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02442206
Sponsor's protocol ID: CQVA149ADE05
Other IDs: 2014-004680-21, 2014
Acronym: CLAIM
Status last verified: Dec 2018
First submitted: 6 May 2015
Last updated: 3 Jan 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 30641027
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.
PubMed 29477448

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 3 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT02442206
Acronym / sponsor ID: CLAIM / CQVA149ADE05
Conditions: Chronic Obstructive Pulmonary Disease, COPD
Keywords: QVA149, cardiac function, ventricular enddiastolic volume, hyperinflated COPD patients
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 62 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 18 May 2015 (actual)
Primary completion: 20 Apr 2017 (actual)
Study completion: 15 May 2017 (actual)
First posted: 13 May 2015 (estimated)
Results: Posted 3 Dec 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Treatment sequence 1	Experimental	Drug: QVA149, Drug: PlaceboQVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43
Treatment sequence 2	Experimental	Drug: QVA149, Drug: PlaceboPlacebo from day 1 to day 15 followed by QVA149 from day 29 to day 43

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
QVA149Also: UltibroQVA149 capsules 100/50 µg for inhalation via Concept-1-inhaler, taken once daily	Drug	Treatment sequence 1, Treatment sequence 2
PlaceboPlacebo to QVA140 capsules 100/50 µg for inhalation via Concept-1-inhaler, taken once daily	Drug	Treatment sequence 1, Treatment sequence 2

Primary outcome

Change in Left Ventricular End-diastolic Volume (LVEDV)
Time frame: 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.

11 secondary outcomes

Change in Forced Expiratory Volume in One Second (FEV1).
Time frame: Baseline, week 2
Change in Forced Vital Capacity (FVC).
Time frame: Baseline, week 2
Change in Inspiratory Capacity (IC) at Each Time-point
Time frame: Baseline, week 2
Change in Total Lung Capacity (TLC)
Time frame: Baseline, week 2
Change in Residual Volume (RVol)
Time frame: Baseline, week 2
Change in Specific Airway Resistance (sRaw)
Time frame: Baseline, week 2
Change in Functional Residual Capacity (FRC)
Time frame: Baseline, week 2
Change in Right Ventricular (RV) and Left Ventricular (LV) Ejection Fraction (EF)
Time frame: Baseline, week 2
Change in Left and Right Ventricular End-systolic Volume
Time frame: Baseline, week 2
Change in Right Ventricular Enddiastolic Volume
Time frame: Baseline, week 2
Cardiac Output at Each Time-point, Left and Right Ventricular Cardiac Output (LVCO and RVCO)
Time frame: week 2

Results and safety

Results posted to the registry on 3 Dec 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Sequence 1	30	29
Treatment Sequence 2	32	29

Primary outcome: Change in Left Ventricular End-diastolic Volume (LVEDV)

Time frame: Baseline, week 2. Mean (Standard Deviation). Unit: ML

Measure	QVA149 n = 57	Placebo n = 59
Value	11.873 (14.3215)	-0.954 (12.2463)

QVA149 vs Placebo: Mean Difference (Net): 10.270 (95% CI 6.209 to 14.331), p <0.0001, ANOVA

Population analysed: 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

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: For the study duration of about 13 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
QVA149 (110/50)	1 of 59 (1.7%)	27 of 59 (45.8%)	0 of 59
Placebo	2 of 61 (3.3%)	17 of 61 (27.9%)	0 of 61
All Patients	2 of 62 (3.2%)	40 of 62 (64.5%)	0 of 62

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30641027Vogel-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.
Derived from this study: PubMed 29477448Hohlfeld 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing QVA149 in people with Chronic Obstructive Pulmonary Disease, COPD, run by Novartis Pharmaceuticals at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Left Ventricular End-diastolic Volume (LVEDV) (time frame: Baseline, week 2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02442206, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2019.