Aortic StenosisPhase 2MELVASNCT02076711
Myocardial Efficiency of the Left Ventricle in Asymptomatic Patients With Aortic Valve Stenosis - a Prognostic Marker and a Target for Intervention?
A Phase 2 study testing Metoprololsuccinate in people with Aortic Stenosis, run by Aarhus University Hospital at 1 site in Denmark.
Trial summary
Background - Aortic valve stenosis (AS) is the most common heart valve disease among adults in the Western world with a prevalence of 3 % in people older than 75 years of age. AS usually deteriorates over time leading to heart failure, with high mortality if aortic valve replacement (AVR) is not performed. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Aortic Stenosis
- What is being tested?
- Metoprololsuccinate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2013to Sep 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aortic valve area ≤1,2 cm2 and/or transaortic maximal velocity (VmaxAO) of 3,0-5,0 m/s
- Sinus rhythm >60/min after 5 minutes of rest
- LVEF >≥50%
- Male or female
- Age 20-100 years old
- Safe birth control management for women of childbearing potential.
- Negative urine-HCG for women of childbearing potential
- Ability to understand the written patient information and to give informed consent
Who cannot join
- Systolic BP <100 mmHg after 5 minutes of rest
- Left ventricular posterior wall thickness >17 mm
- Signs or history of major myocardial infarction and/or severe ischemic heart disease
- Severe asthma or chronic obstructive pulmonary disease
- New York Heart Association (NYHA) classification > I due to AS
- NYHA > II due to non-cardiac causes
Show all 19Show fewer
- 2ᵒ or 3ᵒ atrioventricular block
- Ongoing beta-blocker therapy
- Ongoing verapamil or diltiazem therapy
- Ongoing monoamine oxidase inhibitors therapy (except MAO-B-inhibitors)
- Sick sinus syndrome
- Atrial fibrillation or fluttering
- Lack of stable sinus rhythm
- Pheochromocytoma
- Severe peripheral vascular disease
- Intolerance of Metoprolol succinate or its excipients
- Other disease or treatment making subject unsuitable for study participation
- Intolerance of tracer used for [11C]acetate PET recordings
- Participation in other intervention study
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Aarhus University Hospital, Department of Cardiology, Brendstrupgaardsvej 100
Aarhus N, 8200
About this study
Background - Aortic valve stenosis (AS) is the most common heart valve disease among adults in the Western world with a prevalence of 3 % in people older than 75 years of age. AS usually deteriorates over time leading to heart failure, with high mortality if aortic valve replacement (AVR) is not performed. Thus optimal timing of AVR is crucial, but can be challenging. Increasing life expectancy in our society will augment the therapeutic and socio economic impact of AS disease on our health care system. Therefore, new techniques for monitoring asymptomatic AS patients are needed. A potential approach is monitoring of LV myocardial efficiency (mechanical work/oxygen consumption). These measures have been suggested to be involved in the progression of non-valvular heart failure and closely related to prognosis, but never applied in a larger population of patients with AS. At present there are no recognized pharmacological treatments of AS. It is known that beta-blocker treatment in non-valvular systolic heart failure reduce heart rate, improves LV myocardial efficiency and reduces mortality. However, in patients with AS, the effects of beta-blockers are unknown.
Hypotheses - Treatment with the beta-blocker metoprolol succinate in patients with asymptomatic moderate to severe AS has beneficial effects on LV myocardial oxidative metabolism, myocardial efficiency and contractile function.
Read more
Objectives - To investigate if beta-blocker treatment in patients with moderate to severe, asymptomatic AS has beneficial effects on LV myocardial efficiency, contractile function and physical performance.
Design - A randomized double blind placebo controlled intervention trial. 40 patients with asymptomatic AS will be randomized to either per oral metoprolol succinate (N = 20) or placebo (N= 20) for 22 weeks.
Primary objective - Changes in myocardial efficiency
Secondary objectives - Myocardial oxygen consumption, Myocardial perfusion at rest, LV myocardial function, LVmass, Aortic valve area and transaortic valve velocities, 6 minute walking distance, N-terminal prohormone of brain natriuretic peptide, Quality of life (estimated by Minnesota living with heart failure questionnaire), LV wall stress
Methods - Patients will undergo echocardiography (resting and exercise), [11C]acetate PET and cardiac magnetic resonance imaging.
- Conditions
- Aortic Stenosis
- Being tested
- Metoprololsuccinate, Placebo
- Keywords
- Aortic Stenosis, Myocardial efficiency
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetoprololsuccinateDrug
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Active | Active comparator | Metoprololsuccinate Receives: Drug: Metoprololsuccinate |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
LV myocardial efficiency
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
Secondary outcomes (10)
LV oxygen consumption
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
LV perfusion
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
LV myocardial function
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
LVmass
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
Aortic valve area
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
Transaortic valve velocities
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
6 minute walking distance
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
N-terminal prohormone of brain natriuretic peptide
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
Quality of life - estimated by Minnesota living with heart failure questionnaire
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
LV wall stress
Measured: Changes will be evaluated after an expected average of 22 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2014 (estimated)
- Study startJun 2013
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Henrik Wiggers, Aarhus University Hospital
- Investigators
- Henrik Wiggers, DMSc, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02076711
- Sponsor's protocol ID
- 201300114731
- Acronym
- MELVAS
- Status last verified
- Nov 2015
- First submitted
- 27 Feb 2014
- Last updated
- 11 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hansson NH, Sorensen J, Harms HJ, Kim WY, Nielsen R, Tolbod LP, Frokiaer J, Bouchelouche K, Dodt KK, Sihm I, Poulsen SH, Wiggers H. Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients: A Randomized Trial. Circ Cardiovasc Imaging. 2017 Oct;10(10):e006557. doi: 10.1161/CIRCIMAGING.117.006557.
PubMed 28956773
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Myocardial Efficiency of the Left Ventricle in Asymptomatic Patients With Aortic Valve Stenosis - a Prognostic Marker and a Target for Intervention?
- ClinicalTrials.gov ID
- NCT02076711
- Acronym / sponsor ID
- MELVAS / 201300114731
- Conditions
- Aortic Stenosis
- Keywords
- Aortic Stenosis, Myocardial efficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 4 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background - Aortic valve stenosis (AS) is the most common heart valve disease among adults in the Western world with a prevalence of 3 % in people older than 75 years of age. AS usually deteriorates over time leading to heart failure, with high mortality if aortic valve replacement (AVR) is not performed. Thus optimal timing of AVR is crucial, but can be challenging. Increasing life expectancy in our society will augment the therapeutic and socio economic impact of AS disease on our health care system. Therefore, new techniques for monitoring asymptomatic AS patients are needed. A potential approach is monitoring of LV myocardial efficiency (mechanical work/oxygen consumption). These measures have been suggested to be involved in the progression of non-valvular heart failure and closely related to prognosis, but never applied in a larger population of patients with AS. At present there are no recognized pharmacological treatments of AS. It is known that beta-blocker treatment in non-valvular systolic heart failure reduce heart rate, improves LV myocardial efficiency and reduces mortality. However, in patients with AS, the effects of beta-blockers are unknown.
Hypotheses - Treatment with the beta-blocker metoprolol succinate in patients with asymptomatic moderate to severe AS has beneficial effects on LV myocardial oxidative metabolism, myocardial efficiency and contractile function.
Objectives - To investigate if beta-blocker treatment in patients with moderate to severe, asymptomatic AS has beneficial effects on LV myocardial efficiency, contractile function and physical performance.
Design - A randomized double blind placebo controlled intervention trial. 40 patients with asymptomatic AS will be randomized to either per oral metoprolol succinate (N = 20) or placebo (N= 20) for 22 weeks.
Primary objective - Changes in myocardial efficiency
Secondary objectives - Myocardial oxygen consumption, Myocardial perfusion at rest, LV myocardial function, LVmass, Aortic valve area and transaortic valve velocities, 6 minute walking distance, N-terminal prohormone of brain natriuretic peptide, Quality of life (estimated by Minnesota living with heart failure questionnaire), LV wall stress
Methods - Patients will undergo echocardiography (resting and exercise), [11C]acetate PET and cardiac magnetic resonance imaging.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Active comparator | Drug: MetoprololsuccinateMetoprololsuccinate |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Aortic valve area ≤1,2 cm2 and/or transaortic maximal velocity (VmaxAO) of 3,0-5,0 m/s
- Sinus rhythm >60/min after 5 minutes of rest
- LVEF >≥50%
- Male or female
- Age 20-100 years old
Key exclusion criteria (19 listed)
- Systolic BP <100 mmHg after 5 minutes of rest
- Left ventricular posterior wall thickness >17 mm
- Signs or history of major myocardial infarction and/or severe ischemic heart disease
- Severe asthma or chronic obstructive pulmonary disease
- New York Heart Association (NYHA) classification > I due to AS
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 |
|---|---|---|
| Metoprololsuccinate | Drug | Active |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
LV myocardial efficiency
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
10 secondary outcomes
LV oxygen consumption
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
LV perfusion
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
LV myocardial function
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
LVmass
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
Aortic valve area
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
Transaortic valve velocities
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
6 minute walking distance
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
N-terminal prohormone of brain natriuretic peptide
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
Quality of life - estimated by Minnesota living with heart failure questionnaire
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
LV wall stress
Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2015.
- Derived from this study: PubMed 28956773Hansson NH, Sorensen J, Harms HJ, Kim WY, Nielsen R, Tolbod LP, Frokiaer J, Bouchelouche K, Dodt KK, Sihm I, Poulsen SH, Wiggers H. Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients: A Randomized Trial. Circ Cardiovasc Imaging. 2017 Oct;10(10):e006557. doi: 10.1161/CIRCIMAGING.117.006557.
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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.
Henrik Wiggers, DMSc principal investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metoprololsuccinate in people with Aortic Stenosis, run by Aarhus University Hospital at 1 site in Denmark.
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 8 inclusion and 19 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 11 Nov 2015. 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 Denmark. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
LV myocardial efficiency (time frame: Changes will be evaluated after an expected average of 22 weeks of treatment). 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 NCT02076711, which also lists 1 linked publication.
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 11 Nov 2015.