Aortic Valve InsufficiencyPhase 4BARNCT01157572
Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation
A Phase 4 study testing Metoprolol in people with Aortic Valve Insufficiency, run by Oslo University Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Aortic Valve Insufficiency
- What is being tested?
- Metoprolol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- No sites listed yet
- Study dates
- Aug 2010to Sep 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Moderate to severe aortic valve insufficiency
- Asymptomatic
Who cannot join
- Arrhythmia
- Other severe valve disease
About this study
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.
Read the 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.
- Conditions
- Aortic Valve Insufficiency
- Being tested
- Metoprolol, Placebo
- Keywords
- Aortic valve insufficiency, Beta-blocker
- Medical subject headings
- Aortic Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetoprololDrug
Patients with moderate to severe aortic valve insufficiency will be randomized to Metoprolol
PlaceboDrug
Patients with moderate to severe aortic valve insufficiency will be randomized to Placebo
| Study group | Role | What they receive |
|---|---|---|
| Metoprolol | Active comparator | Not described Receives: Drug: Metoprolol |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular end-diastolic volume
Measured: 6 months
Secondary outcomes (1)
Left ventricular end-systolic volume
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2010 (estimated)
- Study startAug 2010
- Primary completionAug 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve InsufficiencyStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University Ghent, University Hospital, Gentofte, Copenhagen, University Hospital, Akershus, Haukeland University Hospital
- Responsible party
- Principal investigator, Stig Urheim, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01157572
- Sponsor's protocol ID
- EUDRACTNR: 2007-000518-34
- Acronym
- BAR
- Status last verified
- Sep 2014
- First submitted
- 5 Jul 2010
- Last updated
- 25 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26661319
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation
- ClinicalTrials.gov ID
- NCT01157572
- Acronym / sponsor ID
- BAR / EUDRACTNR: 2007-000518-34
- Conditions
- Aortic Valve Insufficiency
- Keywords
- Aortic valve insufficiency, Beta-blocker
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- University Ghent, University Hospital, Gentofte, Copenhagen, University Hospital, Akershus, Haukeland University Hospital
- Study start
- Aug 2010
- Primary completion
- Aug 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 7 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metoprolol | Active comparator | Drug: Metoprolol |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Moderate to severe aortic valve insufficiency
- Asymptomatic
Key exclusion criteria (2 listed)
- Arrhythmia
- Other severe valve disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetoprololPatients with moderate to severe aortic valve insufficiency will be randomized to Metoprolol | Drug | Metoprolol |
| PlaceboPatients with moderate to severe aortic valve insufficiency will be randomized to Placebo | Drug | Placebo |
Primary outcome
Left ventricular end-diastolic volume
Time frame: 6 months
1 secondary outcome
Left ventricular end-systolic volume
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2014.
- Derived from this study: PubMed 26661319Broch 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metoprolol in people with Aortic Valve Insufficiency, run by Oslo University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left ventricular end-diastolic volume (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01157572, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2014.