Percutaneous or Surgical Repair In Mitral Prolapse And Regurgitation for ≥60 Year-olds (PRIMARY)
- Conditions
- Mitral Valve Regurgitation
- Interventions
- Procedure: Mitral valve repairDevice: Transcatheter edge-to-edge repair
- Registration Number
- NCT05051033
- Lead Sponsor
- Annetine Gelijns
- Brief Summary
This is a prospective, multicenter, open-label, randomized trial comparing mitral valve (MV) transcatheter edge-to-edge repair (TEER) to surgical repair (1:1 ratio) in patients with primary, degenerative mitral regurgitation (MR). The trial will be conducted in the U.S., Canada, Germany and the United Kingdom, and is designed as a strategy trial. Thus, all devices legally marketed for TEER of primary degenerative MR in a particular country are eligible to be used in this trial.
- Detailed Description
The primary aim of this study is to evaluate the long-term effectiveness and safety of MV TEER compared with surgical repair in patients with primary, degenerative MR. The secondary aim is to analyze the relationship between the adequacy of MR correction at one-year post intervention and longer-term clinical outcomes (death, heart failure hospitalizations/urgent care visits, valve re-interventions, and quality of life). The tertiary aim of this trial is to evaluate a range of patient-centered outcomes (quality of life, functional status, and discharge location) of transcatheter edge-to-edge MV repair compared with MV surgical repair in patients with primary, degenerative mitral regurgitation.
The patient population for this trial consists of adult patients with severe, primary degenerative MR for whom the local heart team has verified that an indication for MV intervention is present and for whom both transcatheter edge-to-edge and surgical repair strategies are anatomically feasible.
Because the use of the commercial edge-to-edge mitral repair device in the U.S. is approved only in patients considered to be at prohibitive risk of MV surgery by a heart team, use of such devices in this trial is considered investigational by the FDA. As such, this trial will be conducted under an Investigational Device Exemption (IDE ).
Outcomes will be measured from randomization over a period of 5 years post intervention. The estimated enrollment period is 36 months, and all patients will be followed from randomization for up to 10 years post intervention for particular endpoints. Long-term follow-up will include leveraging administrative datasets linked to clinical trial data.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 450
- Adult patients ≥65 yrs with moderately-severe or severe (3+ or 4+/4+) primary degenerative (Carpentier type II) MR defined by transthoracic echocardiography
- Clinical indication for MV intervention and anatomic candidate for both MV transcatheter edge-to-edge and surgical repair per local heart team assessment
- Patients across the surgical risk spectrum (low, intermediate, and high risk) depending on the local heart team assessment (see 2020 ACC/AHA guidelines for the management of patients with valvular heart disease)
- Patients with AF who meet an indication for concomitant ablation may be included provided the local heart team verifies they are eligible for both catheter-based and surgical ablation.
- Ability to perform 6-minute walk test (6MWT) and complete Kansas City Cardiomyopathy Questionnaire (KCCQ) instrument
- Non-degenerative types of primary MR (e.g., cleft leaflet)
- Secondary or functional MR
- Hypertrophic obstructive cardiomyopathy
- Presence of an IVC filter or pacing/ICD leads that would interfere with TEER per local heart team assessment
- Known allergic reactions to intravenous contrast
- Febrile illness within 30-days prior to randomization
- Any absolute contraindication to transesophageal echocardiography
- Any contraindication to systemic heparinization including active bleeding diatheses, and heparin induced thrombocytopenia
- Patients with CAD requiring revascularization
- Any prior mitral valve intervention or any prior repair of atrial septal defect
- Any prior MV intervention or any prior repair of atrial septal defect
- Need for any of the following concomitant procedures: aortic valve or aortic surgery, tricuspid valve surgery
- Need for any emergency intervention or surgery
- Active endocarditis
- Hemodynamic instability defined as cardiac index <2.0 l/min/m2 or systolic blood pressure <90mmHg or need for inotropic support or any mechanical circulatory support
- Left ventricular ejection fraction <25%
- Intracardiac mass or thrombus
- Co-morbid medical or oncologic condition for which local heart team believes that meaningful survival beyond 2 years is unlikely
- Active substance abuse
- Suspected inability to adhere to follow-up
- Treatment with another investigational drug or other intervention, assessment of which has not completed its primary endpoint or that clinically interferes with the present study endpoints.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Surgical mitral valve repair Mitral valve repair Patients who are randomized to the surgical arm will undergo mitral surgery. Transcatheter edge-to-edge repair Transcatheter edge-to-edge repair In the transcatheter edge-to-edge repair arm, patients will be treated with a commercially-approved edge-to-edge mitral repair device.
- Primary Outcome Measures
Name Time Method All-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 3+ MR (by transthoracic echocardiogram (TTE)) composite score. 3 years post intervention Composite score of all-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 3+ MR (by transthoracic echocardiogram (TTE)) from randomization to a minimum follow-up of 3 years post randomization (including a one-month post intervention blanking period for HF hospitalizations/urgent visits).
Composite score will be expressed as a Z-score - The Z-Score is a statistical measurement of a score's relationship to the mean in a group of scores. A Z-score of 0 is equal to the mean, with negative numbers indicating values lower than the mean and positive values higher than the mean.
- Secondary Outcome Measures
Name Time Method Procedure failure 10 years post randomization Procedure failure defined as residual moderately severe or severe (3+ or 4+/4+) MR at the end of the procedure, or conversion of a TEER to an open surgical repair or replacement, or conversion of a surgical mitral valve repair to a mitral valve replacement procedure.
All-cause mortality 10 years post intervention All-cause mortality from randomization through 10 years post intervention
Adequacy of MR correction one year post intervention Adequacy of MR correction at one year post intervention, defined as \< 2+ MR as assessed by TTE
Valve re-interventions 10 years post intervention Valve re-interventions through 10 years post intervention
Mitral valve gradient through 5 years post intervention The valve gradient is the difference in pressure on each side of the valve. When a valve is narrowed (a condition called stenosis), the pressure on the front of the valve builds up as blood is forced through the narrow opening. This causes a larger pressure difference between the front and back of the valve. The valve gradient can be used to determine the severity of the valve disorder.
6 Minute Walk Test (6MWT) through 5 years post intervention Functional status as measured by the 6MWT at yearly time intervals over 5 years. 6MT - The distance covered over a time of 6 minutes
Left Ventricular End Diastolic Volume (LVEDV) through 5 years post intervention Left Ventricular end diastolic volume (LVEDV) is the volume of blood in the left ventricle at the end of the diastole or ventricular filling.
Cost through 10 years post intervention Costs associated with the index hospitalization as well as follow-up readmissions will be measured.
Cardiovascular and non-cardiovascular mortality 10 years post intervention Cardiovascular and non-cardiovascular mortality from randomization through 10 years post intervention
Kansas City Cardiomyopathy Questionnaire (KCCQ) up to 10 years post intervention Disease-specific quality of life as measured by the KCCQ at 6-month time intervals up to 5 years. KCCQ has 23 items that map to 7 domains: symptom frequency; symptom burden; symptom stability; physical limitations; social limitations; quality of life; and self-efficacy. The symptom frequency and symptom burden domains are merged into a total symptom score, which can be combined with the physical limitation domain to create a clinical summary score. All scores are scaled 0 to 100, with higher scores indicating better health outcome.
MR grade through 5 years post intervention Mitral Regurgitation (MR) grade as mild, moderate, or severe. (grade I-IV, with higher grade indicating poorer health outcomes.)
Left Ventricular End Systolic Dimension (LVESD) through 5 years post intervention Left ventricular end systolic dimension (LVESD) is the diameter across the left ventricle of the heart at the end of systole, that is, when the heart muscle is maximally contracted, and usually corresponds to its smallest diameter.
Cost-effectiveness through 10 years post intervention A cost-effectiveness analysis (CEA) comparing cumulative costs and quality-adjusted life years (QALYs) of transcatheter edge-to-edge repair vs surgical repair will be performed from U.S., Canadian, German and United Kingdom health care sector perspectives according to national guidelines.
ICU days of index hospitalization through 10 years post intervention Number of ICU days of index hospitalization
Serious or protocol-defined adverse events 5 years post intervention Serious or protocol-defined adverse events, including stroke, acute kidney injury (AKI), and renal failure, through 5 years
Left Ventricular Ejection Fraction (LVEF) through 5 years post intervention Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction.
Left Ventricular End Diastolic Dimension (LVEDD) through 5 years post intervention Left ventricular end diastolic dimension (LVEDD) is the diameter across the left ventricle of the heart at the end of diastole, that is, when the heart muscle is maximally relaxed, and usually corresponds to its largest diameter.
Left Ventricular End Systolic Volume (LVESV) through 5 years post intervention Left Ventricular end systolic volume (LVESV) is the volume of blood in the left ventricle at the end of the systolic ejection phase immediately before the beginning of diastole or ventricular filling.
Forward stroke volume through 5 years post intervention The forward stroke volume is the volume entering the aorta.
EuroQol- 5 Dimension (EQ-5D) through 10 years post intervention Generic QoL as measured by the EuroQol-5D (EQ-5D). The EQ-5D descriptive system is a preference-based HRQL measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The answers given to ED-5D permit to find 243 unique health states or can be converted into EQ- 5D index an utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).
Length of stay (LOS) through 10 years post intervention Length of stay as measured by number of days hospitalized.
Number and reasons for readmissions through 10 years post intervention Number and reasons for readmissions, including for valve re-intervention and readmissions/urgent visits for heart failure
Trial Locations
- Locations (41)
Baylor, Scott and White
🇺🇸Dallas, Texas, United States
Deutsches Herzzentrum Berlin
🇩🇪Berlin, Germany
Kerckhoff Klinik Bad Nauheim
🇩🇪Bad Nauheim, Germany
Lübeck
🇩🇪Lübeck, Germany
London Health Sciences
🇨🇦London, Ontario, Canada
Universitätsklinikum Frankfurt
🇩🇪Frankfurt, Germany
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Virginia Medical Center
🇺🇸Charlottesville, Virginia, United States
Northwell Health
🇺🇸New York, New York, United States
Deutsches Herzzentrum der Charité
🇩🇪Berlin, Germany
Institut Universitaire de Cardiologie et de Pneumologie de Quebec (Laval University)
🇨🇦Quebec City, Quebec, Canada
South Tees Hospitals NHS Foundation Trust
🇬🇧Middlesbrough, United Kingdom
Universitätsklinikum Schleswig-Holstein Campus Kiel
🇩🇪Kiel, Germany
Deutsches Herzzentrum München
🇩🇪München, Germany
Stanford University
🇺🇸Stanford, California, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
Nyph/Cumc
🇺🇸New York, New York, United States
Weill Cornell Medicine/ New York-Presbyterian Hospital
🇺🇸New York, New York, United States
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
Universitätsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Jena
🇩🇪Jena, Germany
West Virginia University Hospital
🇺🇸Morgantown, West Virginia, United States
Schüchtermann-Klinik Bad Rothenfelde
🇩🇪Bad Rothenfelde, Germany
Asklepios Klinik St. Georg Hamburg
🇩🇪Hamburg, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Herzzentrum Leipzig
🇩🇪Leipzig, Germany
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Keck Hospital of the University of Southern California
🇺🇸Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Piedmont Heart Institute
🇺🇸Atlanta, Georgia, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Ochsner Clinic
🇺🇸New Orleans, Louisiana, United States
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
University of Michigan Hospital
🇺🇸Ann Arbor, Michigan, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Brigham and Women's
🇺🇸Boston, Massachusetts, United States
Saint Luke's Hospital of Kansas City/MidAmerica Heart and Lung Surgeons
🇺🇸Kansas City, Missouri, United States
Duke University Hospital
🇺🇸Durham, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States