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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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Medtronic Cardiovascular Identifier:
First received: February 3, 2012
Last updated: April 26, 2016
Last verified: April 2016
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.

Condition Intervention Phase
Severe Aortic Stenosis
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Medtronic CoreValve® Continued Access Study

Resource links provided by NLM:

Further study details as provided by Medtronic Cardiovascular:

Primary Outcome Measures:
  • All-cause Death or Major Stroke [ Time Frame: 12 Months ]

Secondary Outcome Measures:
  • Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)-free survival [ Time Frame: 5 years ]

    MACCE is defined as a composite of:

    • All-cause death
    • Myocardial infarction (MI)
    • All stroke, and
    • Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)

  • The occurrence of individual MACCE components [ Time Frame: 5 years ]
  • Major Adverse Events (MAE) [ Time Frame: 5 years ]
  • Conduction disturbance requiring permanent pacemaker implantation [ Time Frame: 5 years ]
  • Change in NYHA class [ Time Frame: 5 years ]
  • Change in distance walked during 6-minute walk test (6MWT) [ Time Frame: 12 months ]
  • Ratio of days alive out of hospital versus total days alive [ Time Frame: 12 months ]
  • Quality of Life (QoL) change [ Time Frame: 5 years ]

    Using the following measures:

    • Kansas City Cardiomyopathy Questionnaire (KCCQ)
    • SF-12
    • EuroQoL

  • Echocardiographic assessment of valve performance [ Time Frame: 5 years ]

    Using the following measures:

    • Transvalvular mean gradient
    • Effective orifice area
    • Degree of aortic valve regurgitation (transvalvular and paravalvular)

  • Aortic valve disease hospitalization [ Time Frame: 5 years ]
  • Cardiovascular deaths and valve-related deaths [ Time Frame: 5 years ]
  • Strokes (of any severity) and Transient Ischemic Attacks (TIAs) [ Time Frame: 5 years ]
  • Index procedure related MAEs [ Time Frame: 30 days ]
  • Length of index procedure hospital stay [ Time Frame: Admission to discharge ]
    The length of index procedure hospital stay will be summarized for all subjects. Descriptive statistics will be provided. The endpoint is descriptive and no statistical hypothesis test will be performed.

  • Device success [ Time Frame: 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 location

  • Procedural success [ Time Frame: Admission to discharge ]
    Defined as device success and absence of in-hospital MACCE.

  • Evidence of prosthetic valve dysfunction [ Time Frame: 5 years ]

Enrollment: 1690
Study Start Date: February 2012
Estimated Study Completion Date: October 2019
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Extreme Risk: TAVI Iliofemoral
Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Experimental: Extreme Risk: TAVI Non-Iliofemoral
Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Experimental: High Risk: TAVI
High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.


    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:


  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.


  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)


    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.


  31. Transarterial access not able to accommodate an 18Fr sheath.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01531374

  Hide Study Locations
United States, Arizona
Banner Good Samaritan
Phoenix, Arizona, United States, 85006
United States, California
University of Southern California University Hospital
Los Angeles, California, United States, 90033
Kaiser Permanente - Los Angeles Medical Center
Los Angeles, California, United States, 90072
El Camino Hospital
Mountain View, California, United States, 94040
VA Palo Alto Health Care System
Palo Alto, California, United States, 94304
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102
Yale New Haven Hospital
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Washington Hospital Center / Georgetown Hospital
Washington, District of Columbia, United States, 20010
United States, Florida
Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
University of Miami Health System / Jackson Memorial Hospital
Miami, Florida, United States, 33136
United States, Georgia
Piedmont Heart Institute
Atlanta, Georgia, United States, 30309
Saint Joseph's Hospital of Atlanta
Atlanta, Georgia, United States, 30342
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Indiana
St. Vincent Heart Center of Indiana
Indianapolis, Indiana, United States, 46290
United States, Iowa
Iowa Heart Center
Des Moines, Iowa, United States, 50314
United States, Kansas
University of Kansas Hospital
Kansas City, Kansas, United States, 66160
United States, Louisiana
Cardiovascular Institute of the South/Terrebonne General
Houma, Louisiana, United States, 70360
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Health Systems
Ann Arbor, Michigan, United States, 48109
Detroit Medical Center Cardiovascular Institute
Detroit, Michigan, United States, 48201
St. John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Spectrum Health Hospitals
Grand Rapids, Michigan, United States, 49503
United States, New Jersey
Morristown Memorial Hospital
Morristown, New Jersey, United States, 07962
United States, New York
North Shore University Hospital/ Long Island Jewish Hospital
Manhasset, New York, United States, 11030
NYU Langone Medical Center
New York, New York, United States, 10016
The Mount Sinai Medical Center
New York, New York, United States, 10029
Lenox Hill Hospital
New York, New York, United States, 10075
St. Francis Hospital
Roslyn, New York, United States, 11576
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest University - Baptist Medical Center
Winston Salem, North Carolina, United States, 27157
United States, Ohio
University Hospitals - Case Medical Center
Cleveland, Ohio, United States, 44106
The Ohio State University Medical Center - The Richard M. Ross Heart Hospital
Columbus, Ohio, United States, 43210
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
United States, Pennsylvania
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822
Pinnacle Health
Harrisburg, Pennsylvania, United States, 17043
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Baylor Heart and Vascular Hospital
Dallas, Texas, United States, 75226
Texas Heart Institute at St. Luke's Episcopal Hospital
Houston, Texas, United States, 77030
The Methodist Hospital - The Methodist DeBakey Heart & Vascular Center
Houston, Texas, United States, 77030
United States, Vermont
Fletcher Allen Healthcare
Burlington, Vermont, United States, 05458
United States, Virginia
Inova Fairfax Hospital
Falls Church, Virginia, United States, 22042
United States, Washington
Providence Sacred Heart Medical Center
Spokane, Washington, United States, 99204
United States, Wisconsin
St. Luke's Medical Center - Aurora Health Care
Milwaukee, Wisconsin, United States, 53215
Sponsors and Collaborators
Medtronic Cardiovascular
Principal Investigator: Jeffrey J Popma, MD Beth Israel Deaconess Medical Center
Principal Investigator: David H Adams, MD Icahn School of Medicine at Mount Sinai
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Medtronic Cardiovascular Identifier: NCT01531374     History of Changes
Other Study ID Numbers: 10037989DOC REV 1C
Study First Received: February 3, 2012
Last Updated: April 26, 2016

Keywords provided by Medtronic Cardiovascular:
Valvular Heart Disease
Critical Aortic Stenosis
Severe Aortic Stenosis
Extreme Risk
High Risk
Aortic Valve Replacement

Additional relevant MeSH terms:
Constriction, Pathologic
Aortic Valve Stenosis
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction processed this record on April 28, 2017