Mitral Valve InsufficiencyPhase 3SMMART-HFNCT00608140
Effectiveness of Surgical Mitral Valve Repair Versus Medical Treatment for People With Significant Mitral Regurgitation and Non-ischemic Congestive Heart Failure
A Phase 3 study testing Surgical mitral valvuloplasty with placement of annular ring (SMVR) and Optimal medical therapy (OMT) in people with Mitral Valve Insufficiency and Heart Failure, run by Duke University at 9 sites in 2 countries.
Trial summary
Mitral regurgitation (MR), also known as mitral insufficiency, is a condition in which the heart's mitral valve, located between two of the heart's main chambers, does not firmly shut, allowing blood to leak backwards within the heart. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mitral Valve Insufficiency, Heart Failure
- What is being tested?
- Surgical mitral valvuloplasty with placement of annular ring (SMVR) and Optimal medical therapy (OMT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Mar 2008to Mar 2010
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Symptomatic chronic heart failure, New York Heart Association (NYHA) class II to IIIb
- Left ventricular ejection fraction of 0.35 due to non-ischemic etiology
- Evidence by transthoracic echocardiography (TTE) of moderate or severe MR without obvious primary mitral valve pathology
- Peak VO2 less than or equal to 22 ml/kg/min, as obtained at study entry
- Optimal heart failure therapy for at least 6 months prior to study entry
Who cannot join
- Significant coronary artery disease (greater than 75% lesion in any vessel) by coronary angiography or by a history of a prior heart attack
- Heart failure due to active myocarditis, congenital heart disease, or obstructive hypertrophic cardiomyopathy
- Significant ventricular arrhythmias not treated with an implantable defibrillator
- Primary MR due to significant chordal or leaflet abnormalities by TTE
- Other hemodynamically relevant stenotic or regurgitant valvular diseases
- Severe tricuspid regurgitation (TR) (moderate TR is allowed)
Show all 19Show fewer
- Severe pulmonic regurgitation (PR) (moderate PR is allowed)
- Moderate to severe aortic regurgitation
- Any moderate to severe stenotic lesions using American Heart Association/American College of Cardiology (AHA/ACC) criteria 31
- Dependence on chronic inotropic therapy
- Restrictive cardiomyopathy or constrictive pericarditis
- Severe right ventricular dysfunction
- Baseline creatinine greater than or equal to 3 mg/dL or renal replacement therapy (chronic hemodialysis or peritoneal dialysis)
- Poor transthoracic sonographic windows precluding reasonable assessment of LV endocardial borders from apical imaging on TTE
- Inability to perform the spirometric exercise testing
- Significant chronic lung disease that might interfere with the ability to interpret the spirometric measurements, including home oxygen, forced expiratory volume in 1 second (FEV1) less than 1.0 L/min, or exertional hypoxemia with saturations less than 90%
- Any known neoplastic disease other than skin cancer
- Other terminal illness with a life expectancy less than 1 year
- Plan for percutaneous mitral valve procedure
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States8 sites
Morehouse School of Medicine
Atlanta, Georgia, 30310
Brigham and Women's Hospital
Boston, Massachusetts, 02115
University of Vermont - Fletcher Allen Health Care
Burlington, Vermont, 05401
Duke University Medical Center
Durham, North Carolina, 27705
Baylor College of Medicine
Houston, Texas, 77030
Minnesota Heart Failure Network
Minneapolis, Minnesota, 55415
University of Utah Health Sciences Center
Murray, Utah, 84107
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: Surgery Versus Medical Treatment Alone for Patients With Significant Mitral Regurgitation and Non-ischemic Congestive Heart Failure: SMMART-HF
Mitral regurgitation (MR), also known as mitral insufficiency, is a condition in which the heart's mitral valve, located between two of the heart's main chambers, does not firmly shut, allowing blood to leak backwards within the heart. Improper functioning of the mitral valve disrupts the proper flow of blood through the body, resulting in shortness of breath and fatigue. When mild, MR may not pose a significant danger to a person's health, but severe MR may be associated with serious complications, such as heart failure, irregular heart rhythm, and high blood pressure. Although there are treatments for MR, including medication and surgery, more information is needed on the effectiveness of these treatments in people with significant MR. This study will compare the safety and effectiveness of corrective surgery added to optimal medical treatment (OMT) versus OMT alone in treating people with significant MR caused by an enlarged heart.
Read the detailed description
It is estimated that approximately 4 out of 10 people with an enlarged heart due to heart failure develop MR, referred to as secondary MR. This type of MR is caused by enlargement of the left ventricle (LV), one of the heart's main chambers. In turn, the enlargement leads to stretching of certain heart muscles around the mitral valve and of the valve itself. Symptoms of secondary MR may include shortness of breath, fatigue, dizziness, swollen feet, cough, and heart palpitations. Mitral valve repair or replacement surgery is sometimes considered as a treatment option to restore proper heart function in people with secondary MR. Surgical repair with placement of an artificial ring around the mitral valve can help to tighten the valve and add benefit to non-surgical treatments for MR. However, although surgical placement of the ring improves mitral valve function in most people, it is not known whether this surgery helps people live longer and healthier lives. This study will compare the safety and effectiveness of surgical mitral valvuloplasty with placement of an annular ring (SMVR) added to optimal medical treatment (OMT) versus OMT alone in non-ischemic heart failure patients with significant secondary MR.
Participation from baseline through follow-up in this study will last 18 months. All potential participants will initially undergo a transesophageal echocardiogram to confirm the presence of an abnormal mitral valve. Eligible participants will then undergo a number of baseline tests, which will include cardiopulmonary exercise stress testing, a chest wall echocardiogram, blood draw, 6-minute walk test, medical questionnaires, and a physical exam. Next, participants will be randomly assigned to receive immediate open heart surgery with the placement of a mitral valve ring, delayed surgery at least 18 months later, or OMT. Participants assigned to receive immediate surgery will undergo the surgery 2 weeks after baseline testing. Participants assigned to receive OMT will receive treatment with any of the following medication regimens: combination of vasodilator therapy and diuretics, nitrates and nifedipine, and beta-adrenergic blocker therapy. Follow-up visits for all participants will occur at Months 1, 3, 6, 12, and 18 and will include repeat baseline testing. Long-term survival status data may be collected beyond 18 months for some participants.
- Conditions
- Mitral Valve Insufficiency, Heart Failure
- Being tested
- Surgical mitral valvuloplasty with placement of annular ring (SMVR), Optimal medical therapy (OMT)
- Keywords
- Advanced Heart Failure, Non-Ischemic Heart Failure, Mitral Regurgitation, Mitral Valve Replacement, Congestive Heart Failure, Surgical Mitral Valvuloplasty, Dilated Cardiomyopathy, Annular Ring
- Medical subject headings
- Mitral Valve Insufficiency, Heart Failure, Cardiomyopathy, Dilated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical mitral valvuloplasty with placement of annular ring (SMVR)Procedure or surgery
Participants will undergo open heart surgery to mechanically reduce mitral regurgitation (MR). A complete rigid or semi-rigid annular ring will be placed unless specifically contraindicated by intraoperative findings. The ring size will be between 24 mm and 27 mm in the anteroposterior diameter. Annular ring sutures will be placed circumferentially approximately 1 mm off the hinge point between the leaflet and the atrial tissue. The total number of sutures will vary between 4 and 7 sutures anteriorly, while 8 to 12 sutures will be utilized for the posterior segment of the annulus. Additional repair of the mitral apparatus itself will be based on intraoperative findings. Leaflet repair will be performed for significant prolapse. Submitral apparatus repair will be performed for ruptured or significantly elongated chordae as well as significant chordal tethering.
Optimal medical therapy (OMT)Drug
Optimal medical therapy can include, but is not limited to, any of the following treatment regimens: combination of vasodilator therapy and diuretics, nitrates and nifedipine, and beta-adrenergic blocker therapy.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive optimal medical therapy plus surgical mitral valve repair with complete annular ring placement Receives: Procedure: Surgical mitral valvuloplasty with placement of annular ring (SMVR); Drug: Optimal medical therapy (OMT) |
| 2 | Active comparator | Participants will receive optimal medical therapy alone Receives: Drug: Optimal medical therapy (OMT) |
| 3 | Experimental | Participants will receive optimal medical therapy plus 18-month delayed surgical mitral valve repair with complete annular ring placement Receives: Procedure: Surgical mitral valvuloplasty with placement of annular ring (SMVR); Drug: Optimal medical therapy (OMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of Adding SMVR to OMT Alone on LV Remodeling, Specifically LV End-systolic Volume Index (LVESVI)
Measured: Measured at Month 18
Secondary outcomes (6)
Peak VO2
Measured: Measured at Month 18
Change in 6-minute Walk Test
The 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No data were collected for this outcome measure and no analysis was performed.
Measured: Measured at baseline and Month 18 but n/a
Change in Minnesota Living With Heart Failure (MLHF) Score
Change in MLHF score. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed.
Measured: Planned to be measured at baseline and Month 18 but n/a
Total Days Alive and Total Days Not Hospitalized
Total days alive and not hospitalized by 18 months. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed.
Measured: Measured at baseline and Month 18
Total Mortality (All Causes)
Total all-cause mortality at 18 months. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed.
Measured: Measured at Month 18
Perioperative Mortality
Measured: Measured between Days 0 and 30 postsurgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2008 (estimated)
- Study startMar 2008
- Primary completionMar 2010
- Study completionMar 2010
Why it stopped: Unable to recruit sufficient numbers of patients.
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.
- Other trials for Mitral Valve InsufficiencyStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Heart Failure Clinical Research Network
- Responsible party
- Sponsor
- Investigators
- Kerry L. Lee, PhD, Principal investigator, Duke Clinical Research InstituteEugene Braunwald, MD, Study chair, Harvard University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00608140
- Sponsor's protocol ID
- Pro00002860
- Other IDs
- U01HL084904
- Acronym
- SMMART-HF
- Status last verified
- Jul 2013
- First submitted
- 24 Jan 2008
- Last updated
- 4 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surgery Versus Medical Treatment Alone for Patients With Significant Mitral Regurgitation and Non-ischemic Congestive Heart Failure: SMMART-HF
- ClinicalTrials.gov ID
- NCT00608140
- Acronym / sponsor ID
- SMMART-HF / Pro00002860
- Conditions
- Mitral Valve Insufficiency, Heart Failure
- Keywords
- Advanced Heart Failure, Non-Ischemic Heart Failure, Mitral Regurgitation, Mitral Valve Replacement, Congestive Heart Failure, Surgical Mitral Valvuloplasty, Dilated Cardiomyopathy, Annular Ring
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to recruit sufficient numbers of patients.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Heart Failure Clinical Research Network
- Study start
- Mar 2008
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 6 Feb 2008 (estimated)
- Results
- Posted 18 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mitral regurgitation (MR), also known as mitral insufficiency, is a condition in which the heart's mitral valve, located between two of the heart's main chambers, does not firmly shut, allowing blood to leak backwards within the heart. Improper functioning of the mitral valve disrupts the proper flow of blood through the body, resulting in shortness of breath and fatigue. When mild, MR may not pose a significant danger to a person's health, but severe MR may be associated with serious complications, such as heart failure, irregular heart rhythm, and high blood pressure. Although there are treatments for MR, including medication and surgery, more information is needed on the effectiveness of these treatments in people with significant MR. This study will compare the safety and effectiveness of corrective surgery added to optimal medical treatment (OMT) versus OMT alone in treating people with significant MR caused by an enlarged heart.
Detailed description
It is estimated that approximately 4 out of 10 people with an enlarged heart due to heart failure develop MR, referred to as secondary MR. This type of MR is caused by enlargement of the left ventricle (LV), one of the heart's main chambers. In turn, the enlargement leads to stretching of certain heart muscles around the mitral valve and of the valve itself. Symptoms of secondary MR may include shortness of breath, fatigue, dizziness, swollen feet, cough, and heart palpitations. Mitral valve repair or replacement surgery is sometimes considered as a treatment option to restore proper heart function in people with secondary MR. Surgical repair with placement of an artificial ring around the mitral valve can help to tighten the valve and add benefit to non-surgical treatments for MR. However, although surgical placement of the ring improves mitral valve function in most people, it is not known whether this surgery helps people live longer and healthier lives. This study will compare the safety and effectiveness of surgical mitral valvuloplasty with placement of an annular ring (SMVR) added to optimal medical treatment (OMT) versus OMT alone in non-ischemic heart failure patients with significant secondary MR.
Participation from baseline through follow-up in this study will last 18 months. All potential participants will initially undergo a transesophageal echocardiogram to confirm the presence of an abnormal mitral valve. Eligible participants will then undergo a number of baseline tests, which will include cardiopulmonary exercise stress testing, a chest wall echocardiogram, blood draw, 6-minute walk test, medical questionnaires, and a physical exam. Next, participants will be randomly assigned to receive immediate open heart surgery with the placement of a mitral valve ring, delayed surgery at least 18 months later, or OMT. Participants assigned to receive immediate surgery will undergo the surgery 2 weeks after baseline testing. Participants assigned to receive OMT will receive treatment with any of the following medication regimens: combination of vasodilator therapy and diuretics, nitrates and nifedipine, and beta-adrenergic blocker therapy. Follow-up visits for all participants will occur at Months 1, 3, 6, 12, and 18 and will include repeat baseline testing. Long-term survival status data may be collected beyond 18 months for some participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Procedure: Surgical mitral valvuloplasty with placement of annular ring (SMVR), Drug: Optimal medical therapy (OMT)Participants will receive optimal medical therapy plus surgical mitral valve repair with complete annular ring placement |
| 2 | Active comparator | Drug: Optimal medical therapy (OMT)Participants will receive optimal medical therapy alone |
| 3 | Experimental | Procedure: Surgical mitral valvuloplasty with placement of annular ring (SMVR), Drug: Optimal medical therapy (OMT)Participants will receive optimal medical therapy plus 18-month delayed surgical mitral valve repair with complete annular ring placement |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Symptomatic chronic heart failure, New York Heart Association (NYHA) class II to IIIb
- Left ventricular ejection fraction of 0.35 due to non-ischemic etiology
- Evidence by transthoracic echocardiography (TTE) of moderate or severe MR without obvious primary mitral valve pathology
- Peak VO2 less than or equal to 22 ml/kg/min, as obtained at study entry
- Optimal heart failure therapy for at least 6 months prior to study entry
Key exclusion criteria (19 listed)
- Significant coronary artery disease (greater than 75% lesion in any vessel) by coronary angiography or by a history of a prior heart attack
- Heart failure due to active myocarditis, congenital heart disease, or obstructive hypertrophic cardiomyopathy
- Significant ventricular arrhythmias not treated with an implantable defibrillator
- Primary MR due to significant chordal or leaflet abnormalities by TTE
- Other hemodynamically relevant stenotic or regurgitant valvular diseases
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 |
|---|---|---|
| Surgical mitral valvuloplasty with placement of annular ring (SMVR)Participants will undergo open heart surgery to mechanically reduce mitral regurgitation (MR). A complete rigid or semi-rigid annular ring will be placed unless specifically contraindicated by intraoperative findings. The ring size will be between 24 mm and 27 mm in the anteroposterior diameter. Annular ring sutures will be placed circumferentially approximately 1 mm off the hinge point between the leaflet and the atrial tissue. The total number of sutures will vary between 4 and 7 sutures anteriorly, while 8 to 12 sutures will be utilized for the posterior segment of the annulus. Additional repair of the mitral apparatus itself will be based on intraoperative findings. Leaflet repair will be performed for significant prolapse. Submitral apparatus repair will be performed for ruptured or significantly elongated chordae as well as significant chordal tethering. | Procedure or surgery | 1, 3 |
| Optimal medical therapy (OMT)Optimal medical therapy can include, but is not limited to, any of the following treatment regimens: combination of vasodilator therapy and diuretics, nitrates and nifedipine, and beta-adrenergic blocker therapy. | Drug | 1, 2, 3 |
Primary outcome
Effect of Adding SMVR to OMT Alone on LV Remodeling, Specifically LV End-systolic Volume Index (LVESVI)
Time frame: Measured at Month 18
6 secondary outcomes
Peak VO2
Time frame: Measured at Month 18
Change in 6-minute Walk Test
Time frame: Measured at baseline and Month 18 but n/a
Change in Minnesota Living With Heart Failure (MLHF) Score
Time frame: Planned to be measured at baseline and Month 18 but n/a
Total Days Alive and Total Days Not Hospitalized
Time frame: Measured at baseline and Month 18
Total Mortality (All Causes)
Time frame: Measured at Month 18
Perioperative Mortality
Time frame: Measured between Days 0 and 30 postsurgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kerry L. Lee, PhD principal investigator
Duke Clinical Research Institute
Eugene Braunwald, MD study chair
Harvard University
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Surgical mitral valvuloplasty with placement of annular ring (SMVR) and Optimal medical therapy (OMT) in people with Mitral Valve Insufficiency and Heart Failure, run by Duke University at 9 sites in 2 countries.
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 5 inclusion and 19 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: stopped early, as of the sponsor's last update on 4 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Canada. 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. 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 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 18 Jul 2013). 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?
Effect of Adding SMVR to OMT Alone on LV Remodeling, Specifically LV End-systolic Volume Index (LVESVI) (time frame: Measured at Month 18). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Apr 2018.