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.
Sponsor:
Information provided by (Responsible Party):
Medtronic Cardiovascular
ClinicalTrials.gov Identifier:
NCT01531374
First received: February 3, 2012
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

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: Endpoint Classification: Safety/Efficacy Study
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 ] [ Designated as safety issue: Yes ]

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 [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Change in distance walked during 6-minute walk test (6MWT) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Ratio of days alive out of hospital versus total days alive [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Quality of Life (QoL) change [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

    Using the following measures:

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

  • Echocardiographic assessment of valve performance [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
  • Cardiovascular deaths and valve-related deaths [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Strokes (of any severity) and Transient Ischemic Attacks (TIAs) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Index procedure related MAEs [ Time Frame: Number of days from admission to discharge ] [ Designated as safety issue: Yes ]
  • Length of index procedure hospital stay [ Time Frame: Number of days from admission to discharge ] [ Designated as safety issue: Yes ]
  • Device success [ Time Frame: Number of days from admission to discharge ] [ Designated as safety issue: Yes ]

    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: Number of days from admission to discharge ] [ Designated as safety issue: Yes ]
    Defined as device success and absence of in-hospital MACCE.

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

Estimated Enrollment: 4500
Study Start Date: February 2012
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Medtronic CoreValve® System TAVI
Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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 ClinicalTrials.gov identifier: NCT01531374

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

No publications provided

Responsible Party: Medtronic Cardiovascular
ClinicalTrials.gov Identifier: NCT01531374     History of Changes
Other Study ID Numbers: 10037989DOC REV 1C
Study First Received: February 3, 2012
Last Updated: September 11, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 22, 2014