Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement

This study is currently recruiting participants.
Verified August 2013 by Medtronic Cardiovascular
Information provided by (Responsible Party):
Medtronic Cardiovascular Identifier:
First received: November 10, 2010
Last updated: August 27, 2013
Last verified: August 2013

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 high risk for aortic valve surgery and/or very high risk for aortic valve surgery.

Condition Intervention
Severe Aortic Stenosis
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Device: Surgical Aortic Valve Replacement (SAVR)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Medtronic CoreValve® U.S. Pivotal Trial

Resource links provided by NLM:

Further study details as provided by Medtronic Cardiovascular:

Primary Outcome Measures:
  • High Risk Surgical: All-cause Mortality, Extreme Risk: All-cause Death and Major Stroke [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    All-cause Mortality (High Risk Surgical- Medtronic CoreValve® System vs. Surgical Valve), All-cause Death and Major Stroke(Extreme Risk- Medtronic CoreValve® System)

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

    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 ] [ Designated as safety issue: Yes ]
  • Major Adverse Events (MAE) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Conduction disturbance requiring permanent pacemaker implantation [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Change in NYHA class from baseline [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • Change in distance walked during 6-minute walk test (6MWT) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Ratio of days alive out of hospital versus total days alive [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Quality of Life (QoL) change [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Kansas City Cardiomyopathy Questionnaire (KCCQ), SF-12, and EuroQoL

  • Echocardiographic assessment of prosthetic valve performance [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Measured by transvalvular mean gradient, effective orifice area, degree of aortic valve regurgitation (transvalvular and paravalvular)

  • Aortic valve disease hospitalization [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Cardiovascular deaths and valve-related deaths [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Strokes (of any severity) and TIAs [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Index procedure related MAEs [ Time Frame: Numbers of days from admission to discharge ] [ Designated as safety issue: Yes ]
  • Length of index procedure hospital stay [ Time Frame: Numbers of days from admission to discharge ] [ Designated as safety issue: No ]
  • Device success [ Time Frame: Numbers of days from admission to discharge ] [ Designated as safety issue: Yes ]
    Medtronic CoreValve® System subjects only

  • Procedural success [ Time Frame: Numbers of days from admission to discharge ] [ Designated as safety issue: No ]
    Device success and absence of in-hospital MACCE

  • Evidence of prosthetic valve dysfunction [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1650
Study Start Date: November 2010
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Medtronic CoreValve® System TAVI
Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Experimental: Medtronic CoreValve® System TAVI-High Risk
High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Active Comparator: High Risk Surgical Patients: Surgical Aortic Valve Replacement
High Risk Surgical Patients: Surgical Aortic Valve Replacement
Device: Surgical Aortic Valve Replacement (SAVR)
Experimental: Extreme Risk Patients: TAVI Non-Iliofemoral Observational arm
Observation arm of the study of up to 200 subjects.
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

High Risk Surgical Only

1. 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 Only

  1. 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.

    High Risk Surgical and Extreme Risk

  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 catherterization
  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 index procedure.
  2. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the index procedure.
  3. Blood dyscrasias as defined: leukopenia (WBC < 1000mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
  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 Gastrointestinal (GI) bleeding within the past 3 months.
  11. A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated:

    • aspirin
    • Heparin (HIT/HITTS) and bivalirudin (only for Extreme Risk patients)
    • nitinol (titanium or nickel alloy)
    • 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.

    Additional Exclusion for High Risk Surgical only: Subject has been offered surgical aortic valve replacement but declined.


  19. Native aortic annulus size < 18 mm or > 29 mm per the baseline diagnostic imaging.
  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 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 aorta 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.
  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
Please refer to this study by its identifier: NCT01240902

Contact: Gloria Toledo

  Show 45 Study Locations
Sponsors and Collaborators
Medtronic Cardiovascular
Principal Investigator: David H Adams, MD Mount Sinai School of Medicine
Principal Investigator: Jeffrey J Popma, MD Beth Israel Deaconess Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Medtronic Cardiovascular Identifier: NCT01240902     History of Changes
Other Study ID Numbers: MCV-US-2009-01
Study First Received: November 10, 2010
Last Updated: August 27, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Aortic Valve Stenosis
Constriction, Pathologic
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Pathological Conditions, Anatomical processed this record on April 14, 2014