Effectiveness of Surgical Mitral Valve Repair Versus Medical Treatment for People With Significant Mitral Regurgitation and Non-ischemic Congestive Heart Failure

NCT00608140 | Terminated Phase 3 Results DMC

• 2 other identifiers: Pro00002860U01HL084904
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 9

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.

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

Outcome Measures

Primary Outcomes (1)

• Effect of Adding SMVR to OMT Alone on LV Remodeling, Specifically LV End-systolic Volume Index (LVESVI)

  Measured at Month 18

Secondary Outcomes (6)

• Peak VO2

  Measured at Month 18

• Change in 6-minute Walk Test

  Measured at baseline and Month 18 but n/a

• Change in Minnesota Living With Heart Failure (MLHF) Score

  Planned to be measured at baseline and Month 18 but n/a

• Total Days Alive and Total Days Not Hospitalized

  Measured at baseline and Month 18

• Total Mortality (All Causes)

  Measured at Month 18

Study Arms (3)

1

EXPERIMENTAL

Participants will receive optimal medical therapy plus surgical mitral valve repair with complete annular ring placement

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

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

Procedure: Surgical mitral valvuloplasty with placement of annular ring (SMVR); Drug: Optimal medical therapy (OMT)

Interventions

Surgical mitral valvuloplasty with placement of annular ring (SMVR) PROCEDURE

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.

1; 3

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.

1; 2; 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Heart Failure Clinical Research Network: collaborator

Study Sites (9)

Morehouse School of Medicine

Atlanta, Georgia, 30310, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Minnesota Heart Failure Network

Minneapolis, Minnesota, 55415, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah Health Sciences Center

Murray, Utah, 84107, United States

Location

University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Montreal Heart Institute

Montreal, Quebec, H1T - 1C8, Canada

Location

MeSH Terms

Conditions

Mitral Valve Insufficiency; Heart Failure; Cardiomyopathy, Dilated

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Cardiomegaly; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Mary Ann Sellers
• Organization: Duke University

maryann.sellers@duke.edu

919-668-8544

Study Officials

• Kerry L. Lee, PhD

  Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

• Eugene Braunwald, MD

  Harvard University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2008
• First Posted: February 6, 2008
• Study Start: March 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: April 4, 2018
• Results First Posted: July 18, 2013

Record last verified: 2013-07

Locations

US (8); CA (1)