Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation
Overview[ - collapse ][ - ]
| Purpose | 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. |
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| Condition | Aortic Valve Insufficiency |
| Intervention | Drug: Metoprolol Drug: Placebo |
| Phase | Phase 4 |
| Sponsor | Oslo University Hospital |
| Responsible Party | Oslo University Hospital |
| ClinicalTrials.gov Identifier | NCT01157572 |
| First Received | July 5, 2010 |
| Last Updated | February 21, 2014 |
| Last verified | February 2014 |
Tracking Information[ + expand ][ + ]
| First Received Date | July 5, 2010 |
|---|---|
| Last Updated Date | February 21, 2014 |
| Start Date | August 2010 |
| Estimated Primary Completion Date | August 2014 |
| Current Primary Outcome Measures | Left ventricular end-diastolic volume [Time Frame: 6 months] [Designated as safety issue: Yes] |
| Current Secondary Outcome Measures | Left ventricular end-systolic volume [Time Frame: 6 months] [Designated as safety issue: Yes] |
Descriptive Information[ + expand ][ + ]
| Brief Title | Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation |
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| Official Title | Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation |
| 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. |
| Study Type | Interventional |
| Study Phase | Phase 4 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment |
| Condition | Aortic Valve Insufficiency |
| Intervention | Drug: Metoprolol Patients with moderate to severe aortic valve insufficiency will be randomized to Metoprolol Drug: Placebo Patients with moderate to severe aortic valve insufficiency will be randomized to Placebo |
| Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Active, not recruiting |
|---|---|
| Estimated Enrollment | 70 |
| Estimated Completion Date | August 2014 |
| Estimated Primary Completion Date | August 2014 |
| Eligibility Criteria | Inclusion Criteria: - Moderate to severe aortic valve insufficiency - Asymptomatic Exclusion Criteria: - Arrhythmia - Other severe valve disease |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | Not Provided |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01157572 |
|---|---|
| Other Study ID Numbers | EUDRACTNR: 2007-000518-34 |
| Has Data Monitoring Committee | No |
| Information Provided By | Oslo University Hospital |
| Study Sponsor | Oslo University Hospital |
| Collaborators | University Ghent University Hospital, Gentofte, Copenhagen University Hospital, Akershus Haukeland University Hospital |
| Investigators | Not Provided |
| Verification Date | February 2014 |