Clinical trial NCT00608140: Effectiveness of Surgical Mitral Valve Repair Versus Medical Treatment for People With Significant Mitral Regurgitation and Non-ischemic Congestive Heart Failure
Official title: Surgery Versus Medical Treatment Alone for Patients With Significant Mitral Regurgitation and Non-ischemic Congestive Heart Failure: SMMART-HF
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
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
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Heart Failure Clinical Research Network
First posted: 2008-02-06
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)
* 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

Primary outcomes:
measure: Effect of Adding SMVR to OMT Alone on LV Remodeling, Specifically LV End-systolic Volume Index (LVESVI)
timeFrame: Measured at Month 18
Secondary outcomes:
measure: Peak VO2
timeFrame: Measured at Month 18
measure: Change in 6-minute Walk Test
timeFrame: Measured at baseline and Month 18 but n/a
measure: Change in Minnesota Living With Heart Failure (MLHF) Score
timeFrame: Planned to be measured at baseline and Month 18 but n/a
measure: Total Days Alive and Total Days Not Hospitalized
timeFrame: Measured at baseline and Month 18
measure: Total Mortality (All Causes)
timeFrame: Measured at Month 18
measure: Perioperative Mortality
timeFrame: Measured between Days 0 and 30 postsurgery
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Minnesota Heart Failure Network
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Murray
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Burlington
country: United States
facility: University of Vermont - Fletcher Allen Health Care
state: Vermont
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Duke Clinical Research Institute
name: Kerry L. Lee, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard University
name: Eugene Braunwald, MD
role: STUDY_CHAIR
References: