BAR: Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation

Sponsor

Oslo University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01157572

Collaborator

University Ghent (Other), University Hospital, Gentofte, Copenhagen (Other), University Hospital, Akershus (Other), Haukeland University Hospital (Other)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the effect of beta-blocker on left ventricular (LV) remodeling in asymptomatic patients with moderate to severe aortic regurgitation.

Condition or Disease	Intervention/Treatment	Phase
Aortic Valve Insufficiency	Drug: Metoprolol Drug: Placebo	Phase 4

Detailed Description

The left ventricle responds to the volume load of chronic aortic regurgitation (AR) with a series of compensatory mechanisms, including an increase in end-diastolic volume, an increase in chamber compliance that accommodates the increased volume without an increase in filling pressures, and a combination of eccentric and concentric hypertrophy. The greater diastolic volume permits the ventricle to eject a large total stroke volume to maintain forward stroke volume in the normal range. This is accomplished through rearrangement of myocardial fibers with the addition of new sarcomeres and development of eccentric LV hypertrophy. As a consequence left ventricular ejection fraction will remain in the normal range.

The clinical course of chronic aortic regurgitation is characterized by a prolonged phase of stability during which the left ventricle adapts to the volume overload. Eventually myocardial failure ensues through a series of complex events that include changes in myocyte phenotype due to re-expression of fetal genes, cellular apoptosis alteration in the expression and function of contractile proteins and changes in the extracellular matrix.

The role of long-term vasodilator therapy in the care of asymptomatic patients with severe aortic regurgitation is controversial. Vasodilator therapy has been used to reduce the regurgitant volume, afterload, left ventricular volumes, and wall stress in an effort to preserve left ventricular function and reduce left ventricular mass. Thus time to surgical intervention has been found to be delayed by calcium antagonists, ACE-inhibitors and hydralazine, while a more recent study did not find any effect of nifedipine or enalapril on time to surgery or left ventricular volume and function.

The decision to recommend operative intervention to the asymptomatic patient with chronic, severe aortic regurgitation (AR) is very difficult because aortic valve replacement (AVR) continues to entail immediate risk, and biologic and mechanical valves still have problems resulting in significant morbidity and mortality. On the other hand, the mortality rate in asymptomatic patients with AR is very low, and surgery does not improve the quality of life. Thus, the indication in asymptomatic patients must be delayed until changes occur that will predict an increased risk of operative or long-term death after AVR. At present indication for aortic valve replacement is development of symptoms, an increase in left ventricular volume or a decline in left ventricular function.

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation

Study Start Date :

Aug 1, 2010

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metoprolol	Drug: Metoprolol Patients with moderate to severe aortic valve insufficiency will be randomized to Metoprolol
Placebo Comparator: Placebo	Drug: Placebo Patients with moderate to severe aortic valve insufficiency will be randomized to Placebo

Arm

Intervention/Treatment

Active Comparator: Metoprolol

Drug: Metoprolol

Patients with moderate to severe aortic valve insufficiency will be randomized to Metoprolol

Placebo Comparator: Placebo

Drug: Placebo

Patients with moderate to severe aortic valve insufficiency will be randomized to Placebo

Outcome Measures

Primary Outcome Measures

Left ventricular end-diastolic volume [6 months]

Secondary Outcome Measures

Left ventricular end-systolic volume [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Moderate to severe aortic valve insufficiency
Asymptomatic

Exclusion Criteria:

Arrhythmia
Other severe valve disease

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Oslo University Hospital
University Ghent
University Hospital, Gentofte, Copenhagen
University Hospital, Akershus
Haukeland University Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Stig Urheim, MD, PhD, Oslo University Hospital

ClinicalTrials.gov Identifier:

NCT01157572

Other Study ID Numbers:

EUDRACTNR: 2007-000518-34

First Posted:

Jul 7, 2010

Last Update Posted:

Sep 25, 2014

Last Verified:

Sep 1, 2014

Keywords provided by Stig Urheim, MD, PhD, Oslo University Hospital

Aortic valve insufficiency

Beta-blocker

Additional relevant MeSH terms:

Aortic Valve Insufficiency

Ventricular Remodeling

Metoprolol

Study Results

No Results Posted as of Sep 25, 2014