Mitral RegurgitationPhase 2/3P1A1NCT01052428
Molecular Mechanisms of Volume Overload-Aim 1(SCCOR in Cardiac Dysfunction and Disease)
A Phase 2/3 study testing metoprolol succinate (Toprol XL) in people with Mitral Regurgitation, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
The investigators hypothesize that beta-1 receptor blockade (ß1-RB) attenuates extracellular matrix (ECM) degradation and progressive adverse Left Ventricular (LV) remodeling and failure in the volume overload of mitral regurgitation (MR). Read more about this study
- Who is it for?
- Ages 19 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Mitral Regurgitation
- What is being tested?
- metoprolol succinate (Toprol XL)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Jul 2010
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 19 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Significant obstructive coronary artery disease and/or myocardial ischemia on graded exercise test with myocardial perfusion.
- Previous myocardial infarction or percutaneous coronary intervention.
- Hypertrophic cardiomyopathy, congenital or pericardial disease.
- Aortic valve disease (> trace aortic regurgitation or mean gradient > 10 mmHg).
- Mitral stenosis (mean gradient >5 mmHg, valve area < 1.5 cm2).
- Intolerance or contraindication to Beta1-AR blockade.
Show all 15Show fewer
- Renal failure with creatinine > 2.5 mg/dl.
- Hypertension requiring medical treatment or renal artery stenosis.
- Severe comorbidity: liver disease, malignancy, collagen vascular, steroid requirement.
- Pregnancy (negative pregnancy test and effective contraceptive methods are required prior to enrollment of females of childbearing potential).
- Uncontrolled (rate > 120/min) or recent (<4 weeks) atrial fibrillation.
- Routine, regular use of anti-inflammatory medications.
- Severe claustrophobia.
- Presence of a pacemaker or non-removable hearing aid.
- Presence of metal clips in the body.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294-2180
About this study
The investigators hypothesize that beta-1 receptor blockade (ß1-RB) attenuates extracellular matrix (ECM) degradation and progressive adverse Left Ventricular (LV) remodeling and failure in the volume overload of mitral regurgitation (MR). Patients without coronary artery disease and moderate MR, as assessed by color/flow Doppler echocardiography, will be randomized to ß1-RB vs. placebo to address the following aims:
*Aim 1: Establish whether ß1-RB attenuates adverse LV remodeling compared to placebo in patients with non-surgical, chronic MR. Using 3-dimensional magnetic resonance imaging (MRI) and tissue tagging, LV function and geometry will be assessed at baseline and every 6 months for up to 2 years.
Aim 2: Determine whether indices of inflammation correlate with degree of LV remodeling and whether ß1-RB decrease indices of inflammation and collagen turnover. At the time of MRI, blood samples for collagen breakdown products, matrix metalloproteinase (MMP) activity, and markers of excess production of reactive inflammatory species (RIS) will be obtained and related to changes in LV remodeling defined by serial 3-dimensional MRI and tissue tagging.
Read the detailed description
In Western society, the most common causes of chronic mitral regurgitation (MR) are ischemic heart disease and myxomatous degeneration of the valve, resulting in prolapse, ruptured chordae or partial flail leaflet. Current indications for surgery are only for patients with severe MR and either notable symptoms or overt Left Ventricular (LV) dysfunction (ejection fraction < 60%, end-systolic diameter > 40 mm). Therefore, despite the availability of surgery, most patients with MR of moderate severity are not immediate candidates for surgery, warranting analysis of potential beneficial effects of medical treatment. Chronic therapy with vasodilators reduces LV wall stress and thereby delays the need for valve replacement in aortic regurgitation; however, no such data are currently available in patients with chronic MR using standard vasodilators or agents that block the renin angiotensin system (RAS).
In a clinically-relevant dog model of MR, the investigators have shown increased LV ACE and chymase expression, increased LV angiotensin II but, as opposed to pressure overload, there was an absence of fibrosis with net extracellular matrix (ECM) degradation and activation of matrix metalloproteinases (MMPs). However, blockade of the RAS does not improve (and may actually exacerbate) LV remodeling in MR. Interestingly, the investigators and others have shown that ß1-receptor blockade (ß1-RB) is more effective than RAS blockade in attenuating progressive LV remodeling and ECM degradation in MR. Moreover, increased sympathetic drive and inflammation has been identified in patients with chronic MR. ß1-RB reduced plasma markers of inflammation in patients with heart failure and resulted in substantial reverse LV remodeling in patients with heart failure. Taken together, activation of the adrenergic nervous system early in the course of volume overload contributes to increased production of reactive inflammatory species (RIS) and that one mechanism underlying the salutary effects of ß1-blockade may relate to attenuation of myocardial formation of RIS with subsequent beneficial effects on MMP activation and ECM and LV remodeling and function.
- Conditions
- Mitral Regurgitation
- Being tested
- metoprolol succinate (Toprol XL), Placebo
- Keywords
- Chronic MR, Volume Overload, Beta-1 receptor blocker, LV remodelling, LV dimensions, LV systolic function, LV diastolic dysfunction, Cardiac MRI
- Medical subject headings
- Mitral Valve Insufficiency, Edema, Ventricular Dysfunction, Left
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metoprolol succinate (Toprol XL)Drug
Toprol XL 100 mg once a day for 2 years
PlaceboDrug
Placebo 100 mg once a day for 2 years
| Study group | Role | What they receive |
|---|---|---|
| Toprol XL | Active comparator | beta 1 receptor blockade; generic name metoprolol succinate Receives: Drug: metoprolol succinate (Toprol XL) |
| Placebo | Placebo comparator | Pill that looks like Toprol XL but does not have the active ingredients 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 Indexed to Body Surface Area
Left Ventricular End Diastolic Volume Indexed to Body Surface Area: As an indicator of heart size, the blood volume of the heart is related to the body size. The end diastolic volume is the blood volume of the heart at the end of filling, just before contraction. The relation of heart blood volume to body size is more accurate in determining pathology because larger people require a larger heart blood volume. The values that are too high or too low indicate a diseased myocardium.
Measured: 5 visits per Participant over 2 years (about every 6 months)
Left Ventricular End-diastolic Mass Indexed to Left Ventricular End-diastolic Volume
Left Ventricular End-diastolic Mass Indexed to Left Ventricular End-diastolic Volume As an indicator of heart muscle mass and heart blood volume, the mass indexed to end diastolic volume determines whether there is an adequate amount of heart muscle to pump the heart blood volume obtained from a three-dimensional analysis. The values that are too high or too low indicate a diseased myocardium.
Measured: 5 visits per Participant over 2 years (about every 6 months)
Left Ventricular End-Diastolic Radius to Wall Thickness
Left Ventricular End-Diastolic Radius to Wall Thickness As an indicator of heart muscle mass and heart volume chamber diameter, the end-diastolic radius indexed to end diastolic wall thickness determines whether there is an adequate amount of heart muscle to pump the heart blood volume obtained from a two-dimensional analysis. The values that are too high or too low indicate a diseased myocardium.
Measured: 5 visits per Participant over 2 years (about every 6 months)
Left Ventricular End Systolic Volume Indexed to Body Surface Area
Left Ventricular End Systolic Volume Indexed to Body Surface Area As an indicator of heart size, the blood volume of the heart is related to the body size. The end systolic volume is the blood volume of the heart at the end of contraction and is an index of the pump function of the heart. This relation to body size is more accurate in determining pathology because larger people require a larger heart blood volume. The values that are too high or too low indicate a diseased myocardium.
Measured: 5 visits per Participant over 2 years (about every 6 months)
Left Ventricular Ejection Fraction
Left Ventricular Ejection Fraction Is a calculation of heart pump function determined from the volume after complete filling minus the volume after complete contraction divided by the volume after complete filling. A value of 55% or greater is normal.
Measured: 5 visits per Participant over 2 years (about every 6 months)
Systolic Longitudinal Strain
Systolic Longitudinal Strain. By identifying two points on the heart, the strain is the difference between the distance between these two points at the end of filling of the heart and the end of contraction divided by the length at the end of filling. Thus, the measure is like the ejection fraction, however the strain is more localized to a specified segment in the heart muscle. The higher values indicate a healthy heart.
Measured: 5 visits per Participant over 2 years (about every 6 months)
Peak Early Filling Rate: Rate of Change Over Time
Peak Early Filling Rate The peak early filling rate of change is calculated from the slope of the volume during the early filling of the heart with respect to time. The higher values indicate a very healthy heart muscle and lower values are indicative of a very stiff muscle.
Measured: 5 visits per Participant over 2 years (about every 6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2010 (estimated)
- Study startAug 2004
- Primary completionJul 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for Mitral RegurgitationStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), AstraZeneca
- Responsible party
- Principal investigator, Dr. Louis J. Dell'Italia, University of Alabama at Birmingham
- Investigators
- Louis . J. Dell'Italia, M.D, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01052428
- Sponsor's protocol ID
- F040601008
- Acronym
- P1A1
- Status last verified
- Nov 2012
- First submitted
- 15 Jan 2010
- Last updated
- 22 Nov 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
1. Dell'Italia LJ. Mitral Regurgitation. In Hurst The Heart. Eds. O'Rourke, Sclhant, Alexader, Fuster. 11th Edition, Chapter 57 pp 1169-1695, 2004.
Olson LJ, Subramanian R, Ackermann DM, Orszulak TA, Edwards WD. Surgical pathology of the mitral valve: a study of 712 cases spanning 21 years. Mayo Clin Proc. 1987 Jan;62(1):22-34. doi: 10.1016/s0025-6196(12)61522-5.
PubMed 3796056Otto CM. Timing of surgery in mitral regurgitation. Heart. 2003 Jan;89(1):100-5. doi: 10.1136/heart.89.1.100. No abstract available.
PubMed 12482807Wisenbaugh T, Essop R, Rothlisberger C, Sareli P. Effects of a single oral dose of captopril on left ventricular performance in severe mitral regurgitation. Am J Cardiol. 1992 Feb 1;69(4):348-53. doi: 10.1016/0002-9149(92)90232-n.
PubMed 1734647Rothlisberger C, Sareli P, Wisenbaugh T. Comparison of single dose nifedipine and captopril for chronic severe mitral regurgitation. Am J Cardiol. 1994 May 15;73(13):978-81. doi: 10.1016/0002-9149(94)90148-1. No abstract available.
PubMed 8184862Wisenbaugh T, Sinovich V, Dullabh A, Sareli P. Six month pilot study of captopril for mildly symptomatic, severe isolated mitral and isolated aortic regurgitation. J Heart Valve Dis. 1994 Mar;3(2):197-204.
PubMed 8012639Marcotte F, Honos GN, Walling AD, Beauvais D, Blais MJ, Daoust C, Lisbona A, McCans JL. Effect of angiotensin-converting enzyme inhibitor therapy in mitral regurgitation with normal left ventricular function. Can J Cardiol. 1997 May;13(5):479-85.
PubMed 9179087Host U, Kelbaek H, Hildebrandt P, Skagen K, Aldershvile J. Effect of ramipril on mitral regurgitation secondary to mitral valve prolapse. Am J Cardiol. 1997 Sep 1;80(5):655-8. doi: 10.1016/s0002-9149(97)00445-1.
PubMed 9295005Tischler MD, Rowan M, LeWinter MM. Effect of enalapril therapy on left ventricular mass and volumes in asymptomatic chronic, severe mitral regurgitation secondary to mitral valve prolapse. Am J Cardiol. 1998 Jul 15;82(2):242-5. doi: 10.1016/s0002-9149(98)00325-7.
PubMed 9678300Dujardin KS, Enriquez-Sarano M, Bailey KR, Seward JB, Tajik AJ. Effect of losartan on degree of mitral regurgitation quantified by echocardiography. Am J Cardiol. 2001 Mar 1;87(5):570-6. doi: 10.1016/s0002-9149(00)01433-8.
PubMed 11230841Gaasch WH, Aurigemma GP. Inhibition of the renin-angiotensin system and the left ventricular adaptation to mitral regurgitation. J Am Coll Cardiol. 2002 Apr 17;39(8):1380-3. doi: 10.1016/s0735-1097(02)01766-7. No abstract available.
PubMed 11955859Stewart JA Jr, Wei CC, Brower GL, Rynders PE, Hankes GH, Dillon AR, Lucchesi PA, Janicki JS, Dell'Italia LJ. Cardiac mast cell- and chymase-mediated matrix metalloproteinase activity and left ventricular remodeling in mitral regurgitation in the dog. J Mol Cell Cardiol. 2003 Mar;35(3):311-9. doi: 10.1016/s0022-2828(03)00013-0.
PubMed 12676546Perry GJ, Wei CC, Hankes GH, Dillon SR, Rynders P, Mukherjee R, Spinale FG, Dell'Italia LJ. Angiotensin II receptor blockade does not improve left ventricular function and remodeling in subacute mitral regurgitation in the dog. J Am Coll Cardiol. 2002 Apr 17;39(8):1374-9. doi: 10.1016/s0735-1097(02)01763-1.
PubMed 11955858Dell'italia LJ, Balcells E, Meng QC, Su X, Schultz D, Bishop SP, Machida N, Straeter-Knowlen IM, Hankes GH, Dillon R, Cartee RE, Oparil S. Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs. Am J Physiol. 1997 Aug;273(2 Pt 2):H961-70. doi: 10.1152/ajpheart.1997.273.2.H961.
PubMed 9277516Nemoto S, Hamawaki M, De Freitas G, Carabello BA. Differential effects of the angiotensin-converting enzyme inhibitor lisinopril versus the beta-adrenergic receptor blocker atenolol on hemodynamics and left ventricular contractile function in experimental mitral regurgitation. J Am Coll Cardiol. 2002 Jul 3;40(1):149-54. doi: 10.1016/s0735-1097(02)01926-5.
PubMed 12103269
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Mechanisms of Volume Overload-Aim 1(SCCOR in Cardiac Dysfunction and Disease)
- ClinicalTrials.gov ID
- NCT01052428
- Acronym / sponsor ID
- P1A1 / F040601008
- Conditions
- Mitral Regurgitation
- Keywords
- Chronic MR, Volume Overload, Beta-1 receptor blocker, LV remodelling, LV dimensions, LV systolic function, LV diastolic dysfunction, Cardiac MRI
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), AstraZeneca
- Study start
- Aug 2004
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 20 Jan 2010 (estimated)
- Results
- Posted 16 Apr 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that beta-1 receptor blockade (ß1-RB) attenuates extracellular matrix (ECM) degradation and progressive adverse Left Ventricular (LV) remodeling and failure in the volume overload of mitral regurgitation (MR). Patients without coronary artery disease and moderate MR, as assessed by color/flow Doppler echocardiography, will be randomized to ß1-RB vs. placebo to address the following aims:
*Aim 1: Establish whether ß1-RB attenuates adverse LV remodeling compared to placebo in patients with non-surgical, chronic MR. Using 3-dimensional magnetic resonance imaging (MRI) and tissue tagging, LV function and geometry will be assessed at baseline and every 6 months for up to 2 years.
Aim 2: Determine whether indices of inflammation correlate with degree of LV remodeling and whether ß1-RB decrease indices of inflammation and collagen turnover. At the time of MRI, blood samples for collagen breakdown products, matrix metalloproteinase (MMP) activity, and markers of excess production of reactive inflammatory species (RIS) will be obtained and related to changes in LV remodeling defined by serial 3-dimensional MRI and tissue tagging.
Detailed description
In Western society, the most common causes of chronic mitral regurgitation (MR) are ischemic heart disease and myxomatous degeneration of the valve, resulting in prolapse, ruptured chordae or partial flail leaflet. Current indications for surgery are only for patients with severe MR and either notable symptoms or overt Left Ventricular (LV) dysfunction (ejection fraction < 60%, end-systolic diameter > 40 mm). Therefore, despite the availability of surgery, most patients with MR of moderate severity are not immediate candidates for surgery, warranting analysis of potential beneficial effects of medical treatment. Chronic therapy with vasodilators reduces LV wall stress and thereby delays the need for valve replacement in aortic regurgitation; however, no such data are currently available in patients with chronic MR using standard vasodilators or agents that block the renin angiotensin system (RAS).
In a clinically-relevant dog model of MR, the investigators have shown increased LV ACE and chymase expression, increased LV angiotensin II but, as opposed to pressure overload, there was an absence of fibrosis with net extracellular matrix (ECM) degradation and activation of matrix metalloproteinases (MMPs). However, blockade of the RAS does not improve (and may actually exacerbate) LV remodeling in MR. Interestingly, the investigators and others have shown that ß1-receptor blockade (ß1-RB) is more effective than RAS blockade in attenuating progressive LV remodeling and ECM degradation in MR. Moreover, increased sympathetic drive and inflammation has been identified in patients with chronic MR. ß1-RB reduced plasma markers of inflammation in patients with heart failure and resulted in substantial reverse LV remodeling in patients with heart failure. Taken together, activation of the adrenergic nervous system early in the course of volume overload contributes to increased production of reactive inflammatory species (RIS) and that one mechanism underlying the salutary effects of ß1-blockade may relate to attenuation of myocardial formation of RIS with subsequent beneficial effects on MMP activation and ECM and LV remodeling and function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Toprol XL | Active comparator | Drug: metoprolol succinate (Toprol XL)beta 1 receptor blockade; generic name metoprolol succinate |
| Placebo | Placebo comparator | Drug: PlaceboPill that looks like Toprol XL but does not have the active ingredients |
Who may qualify
- Ages
- 19 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (15 listed)
- Significant obstructive coronary artery disease and/or myocardial ischemia on graded exercise test with myocardial perfusion.
- Previous myocardial infarction or percutaneous coronary intervention.
- Hypertrophic cardiomyopathy, congenital or pericardial disease.
- Aortic valve disease (> trace aortic regurgitation or mean gradient > 10 mmHg).
- Mitral stenosis (mean gradient >5 mmHg, valve area < 1.5 cm2).
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 |
|---|---|---|
| metoprolol succinate (Toprol XL)Toprol XL 100 mg once a day for 2 years | Drug | Toprol XL |
| PlaceboPlacebo 100 mg once a day for 2 years | Drug | Placebo |
Primary outcome
Left Ventricular End Diastolic Volume Indexed to Body Surface Area
Time frame: 5 visits per Participant over 2 years (about every 6 months)
Left Ventricular End Diastolic Volume Indexed to Body Surface Area: As an indicator of heart size, the blood volume of the heart is related to the body size. The end diastolic volume is the blood volume of the heart at the end of filling, just before contraction. The relation of heart blood volume to body size is more accurate in determining pathology because larger people require a larger heart blood volume. The values that are too high or too low indicate a diseased myocardium.
Left Ventricular End-diastolic Mass Indexed to Left Ventricular End-diastolic Volume
Time frame: 5 visits per Participant over 2 years (about every 6 months)
Left Ventricular End-diastolic Mass Indexed to Left Ventricular End-diastolic Volume As an indicator of heart muscle mass and heart blood volume, the mass indexed to end diastolic volume determines whether there is an adequate amount of heart muscle to pump the heart blood volume obtained from a three-dimensional analysis. The values that are too high or too low indicate a diseased myocardium.
Left Ventricular End-Diastolic Radius to Wall Thickness
Time frame: 5 visits per Participant over 2 years (about every 6 months)
Left Ventricular End-Diastolic Radius to Wall Thickness As an indicator of heart muscle mass and heart volume chamber diameter, the end-diastolic radius indexed to end diastolic wall thickness determines whether there is an adequate amount of heart muscle to pump the heart blood volume obtained from a two-dimensional analysis. The values that are too high or too low indicate a diseased myocardium.
Left Ventricular End Systolic Volume Indexed to Body Surface Area
Time frame: 5 visits per Participant over 2 years (about every 6 months)
Left Ventricular End Systolic Volume Indexed to Body Surface Area As an indicator of heart size, the blood volume of the heart is related to the body size. The end systolic volume is the blood volume of the heart at the end of contraction and is an index of the pump function of the heart. This relation to body size is more accurate in determining pathology because larger people require a larger heart blood volume. The values that are too high or too low indicate a diseased myocardium.
Left Ventricular Ejection Fraction
Time frame: 5 visits per Participant over 2 years (about every 6 months)
Left Ventricular Ejection Fraction Is a calculation of heart pump function determined from the volume after complete filling minus the volume after complete contraction divided by the volume after complete filling. A value of 55% or greater is normal.
Systolic Longitudinal Strain
Time frame: 5 visits per Participant over 2 years (about every 6 months)
Systolic Longitudinal Strain. By identifying two points on the heart, the strain is the difference between the distance between these two points at the end of filling of the heart and the end of contraction divided by the length at the end of filling. Thus, the measure is like the ejection fraction, however the strain is more localized to a specified segment in the heart muscle. The higher values indicate a healthy heart.
Peak Early Filling Rate: Rate of Change Over Time
Time frame: 5 visits per Participant over 2 years (about every 6 months)
Peak Early Filling Rate The peak early filling rate of change is calculated from the slope of the volume during the early filling of the heart with respect to time. The higher values indicate a very healthy heart muscle and lower values are indicative of a very stiff muscle.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background1. Dell'Italia LJ. Mitral Regurgitation. In Hurst The Heart. Eds. O'Rourke, Sclhant, Alexader, Fuster. 11th Edition, Chapter 57 pp 1169-1695, 2004.
- Background: PubMed 3796056Olson LJ, Subramanian R, Ackermann DM, Orszulak TA, Edwards WD. Surgical pathology of the mitral valve: a study of 712 cases spanning 21 years. Mayo Clin Proc. 1987 Jan;62(1):22-34. doi: 10.1016/s0025-6196(12)61522-5.
- Background: PubMed 12482807Otto CM. Timing of surgery in mitral regurgitation. Heart. 2003 Jan;89(1):100-5. doi: 10.1136/heart.89.1.100. No abstract available.
- Background: PubMed 1734647Wisenbaugh T, Essop R, Rothlisberger C, Sareli P. Effects of a single oral dose of captopril on left ventricular performance in severe mitral regurgitation. Am J Cardiol. 1992 Feb 1;69(4):348-53. doi: 10.1016/0002-9149(92)90232-n.
- Background: PubMed 8184862Rothlisberger C, Sareli P, Wisenbaugh T. Comparison of single dose nifedipine and captopril for chronic severe mitral regurgitation. Am J Cardiol. 1994 May 15;73(13):978-81. doi: 10.1016/0002-9149(94)90148-1. No abstract available.
- Background: PubMed 8012639Wisenbaugh T, Sinovich V, Dullabh A, Sareli P. Six month pilot study of captopril for mildly symptomatic, severe isolated mitral and isolated aortic regurgitation. J Heart Valve Dis. 1994 Mar;3(2):197-204.
- Background: PubMed 9179087Marcotte F, Honos GN, Walling AD, Beauvais D, Blais MJ, Daoust C, Lisbona A, McCans JL. Effect of angiotensin-converting enzyme inhibitor therapy in mitral regurgitation with normal left ventricular function. Can J Cardiol. 1997 May;13(5):479-85.
- Background: PubMed 9295005Host U, Kelbaek H, Hildebrandt P, Skagen K, Aldershvile J. Effect of ramipril on mitral regurgitation secondary to mitral valve prolapse. Am J Cardiol. 1997 Sep 1;80(5):655-8. doi: 10.1016/s0002-9149(97)00445-1.
- Background: PubMed 9678300Tischler MD, Rowan M, LeWinter MM. Effect of enalapril therapy on left ventricular mass and volumes in asymptomatic chronic, severe mitral regurgitation secondary to mitral valve prolapse. Am J Cardiol. 1998 Jul 15;82(2):242-5. doi: 10.1016/s0002-9149(98)00325-7.
- Background: PubMed 11230841Dujardin KS, Enriquez-Sarano M, Bailey KR, Seward JB, Tajik AJ. Effect of losartan on degree of mitral regurgitation quantified by echocardiography. Am J Cardiol. 2001 Mar 1;87(5):570-6. doi: 10.1016/s0002-9149(00)01433-8.
- Background: PubMed 11955859Gaasch WH, Aurigemma GP. Inhibition of the renin-angiotensin system and the left ventricular adaptation to mitral regurgitation. J Am Coll Cardiol. 2002 Apr 17;39(8):1380-3. doi: 10.1016/s0735-1097(02)01766-7. No abstract available.
- Background: PubMed 12676546Stewart JA Jr, Wei CC, Brower GL, Rynders PE, Hankes GH, Dillon AR, Lucchesi PA, Janicki JS, Dell'Italia LJ. Cardiac mast cell- and chymase-mediated matrix metalloproteinase activity and left ventricular remodeling in mitral regurgitation in the dog. J Mol Cell Cardiol. 2003 Mar;35(3):311-9. doi: 10.1016/s0022-2828(03)00013-0.
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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.
Louis . J. Dell'Italia, M.D principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing metoprolol succinate (Toprol XL) in people with Mitral Regurgitation, run by University of Alabama at Birmingham at 1 site in United States.
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 0 inclusion and 15 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 22 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Indexed to Body Surface Area (time frame: 5 visits per Participant over 2 years (about every 6 months)). The study lists 7 primary outcomes in all. 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 NCT01052428, which also lists 37 linked publications.
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 22 Nov 2012.