Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation (BAR)
Primary Purpose
Aortic Valve Insufficiency
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Metoprolol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Aortic Valve Insufficiency focused on measuring Aortic valve insufficiency, Beta-blocker
Eligibility Criteria
Inclusion Criteria:
- Moderate to severe aortic valve insufficiency
- Asymptomatic
Exclusion Criteria:
- Arrhythmia
- Other severe valve disease
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Metoprolol
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Left ventricular end-diastolic volume
Secondary Outcome Measures
Left ventricular end-systolic volume
Full Information
NCT ID
NCT01157572
First Posted
July 5, 2010
Last Updated
September 24, 2014
Sponsor
Oslo University Hospital
Collaborators
University Ghent, University Hospital, Gentofte, Copenhagen, University Hospital, Akershus, Haukeland University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01157572
Brief Title
Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation
Acronym
BAR
Official Title
Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
September 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
Collaborators
University Ghent, University Hospital, Gentofte, Copenhagen, University Hospital, Akershus, Haukeland University Hospital
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aortic Valve Insufficiency
Keywords
Aortic valve insufficiency, Beta-blocker
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metoprolol
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Metoprolol
Intervention Description
Patients with moderate to severe aortic valve insufficiency will be randomized to Metoprolol
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Patients with moderate to severe aortic valve insufficiency will be randomized to Placebo
Primary Outcome Measure Information:
Title
Left ventricular end-diastolic volume
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Left ventricular end-systolic volume
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Moderate to severe aortic valve insufficiency
Asymptomatic
Exclusion Criteria:
Arrhythmia
Other severe valve disease
12. IPD Sharing Statement
Citations:
PubMed Identifier
26661319
Citation
Broch K, Urheim S, Lonnebakken MT, Stueflotten W, Massey R, Fossa K, Hopp E, Aakhus S, Gullestad L. Controlled release metoprolol for aortic regurgitation: a randomised clinical trial. Heart. 2016 Feb;102(3):191-7. doi: 10.1136/heartjnl-2015-308416. Epub 2015 Dec 9.
Results Reference
derived
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Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation
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