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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Aarhus University Hospital
Sponsor:
Information provided by (Responsible Party):
Henrik Wiggers, Aarhus University Hospital
ClinicalTrials.gov Identifier:
NCT02076711
First received: February 27, 2014
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Aortic Stenosis
Drug: Metoprololsuccinate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Myocardial Efficiency of the Left Ventricle in Asymptomatic Patients With Aortic Valve Stenosis - a Prognostic Marker and a Target for Intervention?

Resource links provided by NLM:


Further study details as provided by Aarhus University Hospital:

Primary Outcome Measures:
  • LV myocardial efficiency [ Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • LV oxygen consumption [ Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment ] [ Designated as safety issue: No ]
  • LV perfusion [ Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment ] [ Designated as safety issue: No ]
  • LV myocardial function [ Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment ] [ Designated as safety issue: No ]
  • LVmass [ Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment ] [ Designated as safety issue: No ]
  • Aortic valve area [ Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment ] [ Designated as safety issue: No ]
  • Transaortic valve velocities [ Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment ] [ Designated as safety issue: No ]
  • 6 minute walking distance [ Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment ] [ Designated as safety issue: No ]
  • N-terminal prohormone of brain natriuretic peptide [ Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • LV wall stress [ Time Frame: Changes will be evaluated after an expected average of 22 weeks of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: June 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active
Metoprololsuccinate
Drug: Metoprololsuccinate
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02076711

Contacts
Contact: Henrik Wiggers, DMSc 4522753202 henrikwiggers@dadlnet.dk
Contact: Nils H Hansson, MD 4530293466 nilhan@rm.dk

Locations
Denmark
Aarhus University Hospital, Department of Cardiology, Brendstrupgaardsvej 100 Recruiting
Aarhus N, Denmark, 8200
Contact: Henrik Wiggers, DMSc    +45 22753202    henrikwiggers@dadlnet.dk   
Contact: Nils H Hansson, MD    +45 30293466    nilhan@rm.dk   
Sub-Investigator: Nils H Hansson, MD         
Principal Investigator: Henrik Wiggers, DMSc         
Sponsors and Collaborators
Aarhus University Hospital
Investigators
Principal Investigator: Henrik Wiggers, DMSc
  More Information

No publications provided

Responsible Party: Henrik Wiggers, Senior consultant, Assoc. professor, DMSc, Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT02076711     History of Changes
Other Study ID Numbers: 201300114731
Study First Received: February 27, 2014
Last Updated: February 28, 2014
Health Authority: Denmark: Danish Health and Medicines Authority
Denmark: The Regional Scientific Ethical Committee of Central Denmark Region
Denmark: Unit for "Good Clinical Practice" at Aarhus University Hospital

Keywords provided by Aarhus University Hospital:
Aortic Stenosis
Myocardial efficiency

Additional relevant MeSH terms:
Aortic Valve Stenosis
Constriction, Pathologic
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on July 20, 2014