- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02076711
Myocardial Efficiency of the Left Ventricle in Asymptomatic Patients With Aortic Valve Stenosis - a Prognostic Marker and a Target for Intervention? (MELVAS)
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Aarhus N, Denmark, 8200
- Aarhus University Hospital, Department of Cardiology, Brendstrupgaardsvej 100
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Placebo
|
Placebo
|
ACTIVE_COMPARATOR: Active
Metoprololsuccinate
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
LV myocardial efficiency
Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment
|
Changes will be evaluated after an expected average of 22 weeks of treatment
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
LV oxygen consumption
Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
Changes will be evaluated after an expected average of 22 weeks of treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Henrik Wiggers, DMSc
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 201300114731
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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