NCT02076711: MELVAS

Myocardial Efficiency of the Left Ventricle in Asymptomatic Patients With Aortic Valve Stenosis - a Prognostic Marker and a Target for Intervention?

Completed Phase 2 Last updated 10 November 2015

What this trial tests

Phase 2 trial testing Metoprololsuccinate in Aortic Stenosis in 40 participants. Completed in 1 September 2015.

Timeline

1 June 2013

Primary endpoint
1 September 2015

1 September 2015

Quick facts

Lead sponsor	Aarhus University Hospital
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	40
Start date	1 June 2013
Primary completion	1 September 2015
Estimated completion	1 September 2015
Sites	1 location across Denmark

Drugs / interventions tested

• Metoprololsuccinate — full drug profile →
• Placebo

Conditions studied

• Aortic Stenosis — all drugs for Aortic Stenosis →

Sponsor

Aarhus University Hospital

Who can join

20 and older, any sex, with Aortic Stenosis. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• LV myocardial efficiency
  Time frame: Changes will be evaluated after an expected average of 22 weeks of treatment

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients: A Randomized Trial.
   Hansson NH, Sörensen J, Harms HJ, Kim WY, et al · · 2017 · cited 33× · PMID 28956773 · DOI 10.1161/circimaging.117.006557