Safety and Efficacy Continued Access Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in Very High Risk Subjects and High Risk Subjects Who Need Aortic Valve Replacement
- Conditions
- Severe Aortic Stenosis
- Interventions
- Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
- Registration Number
- NCT01531374
- Lead Sponsor
- Medtronic Cardiovascular
- Brief Summary
The purpose of the study is to evaluate the safety and efficacy of the Medtronic CoreValve® System in the treatment of symptomatic severe aortic stenosis in subjects who have a predicted very high risk and high risk for aortic valve surgery.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2777
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High Risk: Subject must have co-morbidities such that one cardiologist and two cardiac surgeons agree that predicted risk of operative mortality is ≥15% (and predicted operative mortality or serious, irreversible morbidity risk of < 50%) at 30 days.
OR
Extreme Risk: Subject must have co-morbidities such that one cardiologist and two cardiac surgeons agree that medical factors preclude operation, based on a conclusion that the probability of death or serious morbidity exceeds the probability of meaningful improvement. Specifically, the predicted operative risk of death or serious, irreversible morbidity is ≥ 50% at 30 days.
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Subject has senile degenerative aortic valve stenosis with:
- Mean gradient > 40 mmHg, or jet velocity greater than 4.0 m/sec by either resting or dobutamine stress echocardiogram, or simultaneous pressure recordings at cardiac catheterization (either resting or dobutamine stress), AND
- An initial aortic valve area of ≤ 0.8 cm2 (or aortic valve area index ≤ 0.5 cm2/m2) by resting echocardiogram or simultaneous pressure recordings at cardiac catheterization
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Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater.
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The subject or the subject's legal representative has been informed of the nature of the trial, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site.
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The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.
Clinical
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Evidence of an acute myocardial infarction ≤ 30 days before the intended treatment.
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Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the MCS TAVI procedure including bare metal and drug eluting stents.
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Blood dyscrasias as defined: leukopenia (WBC < 1000mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy.
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Untreated clinically significant coronary artery disease requiring revascularization.
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Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
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Need for emergency surgery for any reason.
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Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% as measured by resting echocardiogram.
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Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
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End stage renal disease requiring chronic dialysis or creatinine clearance < 20 cc/min.
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Active GI bleeding that would preclude anticoagulation.
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A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated:
- Aspirin
- Heparin (HIT/HITTS) and bivalirudin
- Nitinol (titanium or nickel)
- Ticlopidine and clopidogrel
- Contrast media
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Ongoing sepsis, including active endocarditis.
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Subject refuses a blood transfusion.
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Life expectancy < 12 months due to associated non-cardiac co-morbid conditions.
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Other medical, social, or psychological conditions that in the opinion of an Investigator precludes the subject from appropriate consent.
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Severe dementia (resulting in either inability to provide informed consent for the trial/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
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Currently participating in an investigational drug or another device trial.
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Symptomatic carotid or vertebral artery disease.
Anatomical
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High Risk:Native aortic annulus size < 20 mm or > 29 mm per the baseline diagnostic imaging (until 23mm valve enrollment completion/closure in the CoreValve® US Pivotal Trial-High Risk Cohort)
OR
Extreme Risk: Native aortic annulus size < 18 mm or > 29 mm per the baseline diagnostic imaging. (High risk and extreme risk upon 23mm valve enrollment completion/closure in the CoreValve® US Pivotal Trial-High Risk Cohort)
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Pre-existing prosthetic heart valve any position.
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Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation (3-4+)).
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Moderate to severe (3-4+) or severe (4+) mitral or severe (4+) tricuspid regurgitation.
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Moderate to severe mitral stenosis.
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Hypertrophic obstructive cardiomyopathy.
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Echocardiographic evidence of new or untreated intracardiac mass, thrombus or vegetation.
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Severe basal septal hypertrophy with an outflow gradient.
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Aortic root angulation (angle between plane of aortic valve annulus and horizontal plane/vertebrae) > 70° (for femoral and left subclavian/axillary access) and > 30° (for right subclavian/axillary access).
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Ascending aorta diameter >43 mm if the aortic annulus diameter is 23-29 mm; ascending aortic diameter > 40 mm if the aortic annulus diameter is 20-23 mm; or an ascending aorta diameter > 34 mm if the aortic annulus diameter is 18-20 mm (Extreme Risk only until 23 mm valve enrollment completion/closure in the CoreValve® US Pivotal Trial-High Risk Cohort).
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Congenital bicuspid or unicuspid valve verified by echocardiography.
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Sinus of valsalva anatomy that would prevent adequate coronary perfusion.
Vascular
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Transarterial access not able to accommodate an 18Fr sheath.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Extreme Risk: TAVI Iliofemoral Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access High Risk: TAVI Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Extreme Risk: TAVI Non-Iliofemoral Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access
- Primary Outcome Measures
Name Time Method Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality 1 year All-cause Death or Major Stroke (Extreme Risk- Medtronic CoreValve® System); All-cause Mortality (High Risk Surgical- Medtronic CoreValve® System vs. Surgical Valve)
- Secondary Outcome Measures
Name Time Method Conduction Disturbance Requiring Permanent Pacemaker Implantation 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete. Change From Baseline in Distance Walked During 6-Minute Walk Test (6MWT) Baseline to 30 days, baseline to 1 year Change in distance walked during 6MWT from baseline
Major Adverse Events (MAEs) 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete. MAEs Include:
* MACCE
* Acute Kidney Injury
* Cardiac Tamponade
* Prosthetic Valve Dysfunction
* Cardiogenic Shock
* Valve Endocarditis
* Life-Threatening, Disabling or Major Bleeding
* Major Vascular Complication
* Cardiac Perforation
* Device Migration/Valve EmbolismQuality of Life (QoL) Change 30 day, 6 month, 1 year. The 2-5 year outcome data will be reported once data set is complete. QoL summary score change from baseline using the following measures:
* Kansas City Cardiomyopathy Questionnaire (KCCQ): Quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
* 12 Item Short Form Health Survey (SF-12): Measures functional health and well-being. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
* European QoL (EQ-5D): Measures 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that can be converted to utilities using an algorithm. Utilities range from 0 to 1, with 1 representing perfect health, and 0 corresponding to the worst imaginable health state.Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete. MACCE is defined as a composite of:
* All-Cause Death
* Myocardial Infarction (MI)
* All Stroke
* Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)Ratio of Days Alive Out of Hospital at 365 Days Post Procedure Versus Total Days Alive 1 year Echocardiographic Assessment of Valve Performance 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete. Using the following measure:
- Degree of Aortic Valve Regurgitation (Transvalvular and Paravalvular) analyzed overall per Extreme Risk or High Risk. Iliofemoral access and non-iliofemoral access are not reported separate because this is a valve performance measurement.Cardiovascular Deaths and Valve-Related Deaths 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete. Strokes and Transient Ischemic Attacks (TIAs) 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete. Strokes (of any severity) and TIAs
Index Procedure Related MAEs Procedure Length of Index Procedure Hospital Stay Number of days from admission to discharge The Occurrence of Individual MACCE Components 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete. Individual MACCE Components Include:
* All Cause Mortality
* MI
* All stroke
* Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)Change From Baseline in NYHA Class Baseline to 30 days, baseline to 6 months, baseline to 1 year. The 2-5 year outcome data will be reported once data set is complete. Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.
NYHA Classification:
Class I: Subjects with cardiac disease but without resulting limitations of physical activity.
Class I: Subjects with cardiac disease resulting in slight limitation of physical activity.
Class III: Subjects with cardiac disease resulting in marked limitation of physical activity.
Class IV: Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort.Aortic Valve Hospitalizations 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete. Device Success Number of days from admission to discharge Defined as:
* Successful vascular access, delivery and deployment of the device, and successful retrieval of the delivery system,
* Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function),
* Intended performance of the prosthetic valve (aortic valve area \> 1.2 cm2 for 26, 29 and 31mm valves, ≥ 0.9 cm2 for 23mm valve (by echocardiography using the continuity equation) and mean aortic valve gradient \< 20 mmHg or peak velocity \< 3 m/sec, without moderate or severe prosthetic valve aortic regurgitation)
* Only one valve implanted in the proper anatomical locationProcedural Success Number of days from admission to discharge Defined as device success and absence of in-hospital MACCE.
Prosthetic Valve Dysfunction (PVD) 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete. PVD was defined according to VARC using the site reported echocardiography assessments including aortic regurgitation (AR) and aortic stenosis (AS) evaluations. Total AR reported as moderate or severe was considered PVD. AS was defined as significant stenosis and considered PVD if one of the following was met:
* Peak velocity \>4 m/s
* Mean gradient \>35 mmHg
* EOA \< 0.8 cm2
* TVIV1 / TVIV2 \< 0.25
Trial Locations
- Locations (45)
University of Southern California University Hospital
🇺🇸Los Angeles, California, United States
Kaiser Permanente - Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
El Camino Hospital
🇺🇸Mountain View, California, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Piedmont Heart Institute
🇺🇸Atlanta, Georgia, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
Texas Heart Institute at St. Luke's Episcopal Hospital
🇺🇸Houston, Texas, United States
The Methodist Hospital - The Methodist DeBakey Heart & Vascular Center
🇺🇸Houston, Texas, United States
University Hospitals - Case Medical Center
🇺🇸Cleveland, Ohio, United States
University of Miami Health System / Jackson Memorial Hospital
🇺🇸Miami, Florida, United States
VA Palo Alto Health Care System
🇺🇸Palo Alto, California, United States
Cardiovascular Institute of the South/Terrebonne General
🇺🇸Houma, Louisiana, United States
Iowa Heart Center
🇺🇸Des Moines, Iowa, United States
Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
North Shore University Hospital/ Long Island Jewish Hospital
🇺🇸Manhasset, New York, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
Banner Good Samaritan
🇺🇸Phoenix, Arizona, United States
University of Michigan Health Systems
🇺🇸Ann Arbor, Michigan, United States
Detroit Medical Center Cardiovascular Institute
🇺🇸Detroit, Michigan, United States
St. John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Wake Forest University - Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
St. Luke's Medical Center - Aurora Health Care
🇺🇸Milwaukee, Wisconsin, United States
Washington Hospital Center / Georgetown Hospital
🇺🇸Washington, District of Columbia, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
St. Vincent Heart Center of Indiana
🇺🇸Indianapolis, Indiana, United States
Saint Joseph's Hospital of Atlanta
🇺🇸Atlanta, Georgia, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Spectrum Health Hospitals
🇺🇸Grand Rapids, Michigan, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
St. Francis Hospital
🇺🇸Roslyn, New York, United States
The Mount Sinai Medical Center
🇺🇸New York, New York, United States
Lenox Hill Hospital
🇺🇸New York, New York, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
The Ohio State University Medical Center - The Richard M. Ross Heart Hospital
🇺🇸Columbus, Ohio, United States
Pinnacle Health
🇺🇸Harrisburg, Pennsylvania, United States
Baylor Heart and Vascular Hospital
🇺🇸Dallas, Texas, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Providence Sacred Heart Medical Center
🇺🇸Spokane, Washington, United States