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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01531374
Other study ID # 10037989DOC REV 1C
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date February 21, 2012
Est. completion date November 18, 2019

Study information

Verified date October 2022
Source Medtronic Cardiovascular
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 2777
Est. completion date November 18, 2019
Est. primary completion date November 2015
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility Inclusion Criteria: 1. 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. 2. 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 3. Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater. 4. 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. 5. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits. Exclusion Criteria: Clinical 1. Evidence of an acute myocardial infarction = 30 days before the intended treatment. 2. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the MCS TAVI procedure including bare metal and drug eluting stents. 3. Blood dyscrasias as defined: leukopenia (WBC < 1000mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy. 4. Untreated clinically significant coronary artery disease requiring revascularization. 5. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support. 6. Need for emergency surgery for any reason. 7. Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% as measured by resting echocardiogram. 8. Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA). 9. End stage renal disease requiring chronic dialysis or creatinine clearance < 20 cc/min. 10. Active GI bleeding that would preclude anticoagulation. 11. 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 12. Ongoing sepsis, including active endocarditis. 13. Subject refuses a blood transfusion. 14. Life expectancy < 12 months due to associated non-cardiac co-morbid conditions. 15. Other medical, social, or psychological conditions that in the opinion of an Investigator precludes the subject from appropriate consent. 16. 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). 17. Currently participating in an investigational drug or another device trial. 18. Symptomatic carotid or vertebral artery disease. Anatomical 19. 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) 20. Pre-existing prosthetic heart valve any position. 21. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation (3-4+)). 22. Moderate to severe (3-4+) or severe (4+) mitral or severe (4+) tricuspid regurgitation. 23. Moderate to severe mitral stenosis. 24. Hypertrophic obstructive cardiomyopathy. 25. Echocardiographic evidence of new or untreated intracardiac mass, thrombus or vegetation. 26. Severe basal septal hypertrophy with an outflow gradient. 27. 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). 28. 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). 29. Congenital bicuspid or unicuspid valve verified by echocardiography. 30. Sinus of valsalva anatomy that would prevent adequate coronary perfusion. Vascular 31. Transarterial access not able to accommodate an 18Fr sheath.

Study Design


Intervention

Device:
Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)


Locations

Country Name City State
United States University of Michigan Health Systems Ann Arbor Michigan
United States Piedmont Heart Institute Atlanta Georgia
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 University of Vermont Medical Center Burlington Vermont
United States University Hospitals - Case Medical Center Cleveland Ohio
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 Baylor Heart and Vascular Hospital Dallas Texas
United States Geisinger Medical Center Danville Pennsylvania
United States Iowa Heart Center Des Moines Iowa
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 Inova Fairfax Hospital Falls Church Virginia
United States Spectrum Health Hospitals Grand Rapids Michigan
United States Pinnacle Health Harrisburg Pennsylvania
United States Hartford Hospital Hartford Connecticut
United States Cardiovascular Institute of the South/Terrebonne General Houma Louisiana
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 St. Vincent Heart Center of Indiana Indianapolis Indiana
United States University of Kansas Hospital Kansas City Kansas
United States Kaiser Permanente - Los Angeles Medical Center Los Angeles California
United States University of Southern California University Hospital Los Angeles California
United States North Shore University Hospital/ Long Island Jewish Hospital Manhasset New York
United States Loyola University Medical Center Maywood Illinois
United States University of Miami Health System / Jackson Memorial Hospital Miami Florida
United States Mount Sinai Medical Center Miami Beach Florida
United States St. Luke's Medical Center - Aurora Health Care Milwaukee Wisconsin
United States Morristown Memorial Hospital Morristown New Jersey
United States El Camino Hospital Mountain View California
United States Vanderbilt University Medical Center Nashville Tennessee
United States Yale New Haven Hospital New Haven Connecticut
United States Lenox Hill Hospital New York New York
United States NYU Langone Medical Center New York New York
United States The Mount Sinai Medical Center New York New York
United States VA Palo Alto Health Care System Palo Alto California
United States Banner Good Samaritan Phoenix Arizona
United States University of Pittsburgh Medical Center Pittsburgh Pennsylvania
United States St. Francis Hospital Roslyn New York
United States Providence Sacred Heart Medical Center Spokane Washington
United States Washington Hospital Center / Georgetown Hospital Washington District of Columbia
United States Wake Forest University - Baptist Medical Center Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Medtronic Cardiovascular

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality All-cause Death or Major Stroke (Extreme Risk- Medtronic CoreValve® System); All-cause Mortality (High Risk Surgical- Medtronic CoreValve® System vs. Surgical Valve) 1 year
Secondary Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) 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)
30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary The Occurrence of Individual MACCE Components 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)
30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary Major Adverse Events (MAEs) 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 Embolism
30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary 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.
Secondary Change From Baseline in NYHA Class 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.
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.
Secondary Change From Baseline in Distance Walked During 6-Minute Walk Test (6MWT) Change in distance walked during 6MWT from baseline Baseline to 30 days, baseline to 1 year
Secondary Ratio of Days Alive Out of Hospital at 365 Days Post Procedure Versus Total Days Alive 1 year
Secondary Quality of Life (QoL) Change 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.
30 day, 6 month, 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary Echocardiographic Assessment of Valve Performance Using the following measure:
• Effective Orifice Area (EOA) 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.
30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary Echocardiographic Assessment of Valve Performance Using the following measure:
• Transvalvular Mean Gradient 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.
30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary Echocardiographic Assessment of Valve Performance 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.
30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary Aortic Valve Hospitalizations 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary 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.
Secondary Strokes and Transient Ischemic Attacks (TIAs) Strokes (of any severity) and TIAs 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary Index Procedure Related MAEs Procedure
Secondary Length of Index Procedure Hospital Stay Number of days from admission to discharge
Secondary Device Success 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 location
Number of days from admission to discharge
Secondary Procedural Success Defined as device success and absence of in-hospital MACCE. Number of days from admission to discharge
Secondary Prosthetic Valve Dysfunction (PVD) 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
30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
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