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. (see Contacts and Locations)
Verified May 2014 by Medtronic Cardiovascular
Sponsor:
Information provided by (Responsible Party):
Medtronic Cardiovascular
ClinicalTrials.gov Identifier:
NCT01240902
First received: November 10, 2010
Last updated: May 30, 2014
Last verified: May 2014

November 10, 2010
May 30, 2014
November 2010
August 2015   (final data collection date for primary outcome measure)
High Risk Surgical: All-cause Mortality, Extreme Risk: All-cause Death or 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 or Major Stroke(Extreme Risk- Medtronic CoreValve® System)
Freedom from Death, Co-Primary Endpoints: Freedom from Death and Major Stroke or a composite of freedom from death, major stroke, number and length of hospitalization for aortic valve disease. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Freedom from Death (Medtronic CoreValve® System vs. Surgical Valve),Co-Primary Endpoints: Freedom from Death and Major Stroke or a composite of freedom from death, major stroke, number and length of hospitalization for aortic valve disease (Medtronic CoreValve® System vs. Optimal Medical Management)
Complete list of historical versions of study NCT01240902 on ClinicalTrials.gov Archive Site
  • 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, and
    • EuroQoL
  • Echocardiographic assessment of prosthetic 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 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: Numbers of days from admission to discharge ] [ Designated as safety issue: Yes ]

    Medtronic CoreValve® System subjects only.

    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 ]

    Medtronic CoreValve® System subjects only.

    Defined as device success and absence of in-hospital MACCE.

  • Evidence of prosthetic valve dysfunction [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Medtronic CoreValve® System subjects only.
  • Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)-free survival [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    Freedom from all cause death, myocardial infarction (MI), major stroke, and reintervention
  • The occurrence of individual MACCE components [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    Freedom from all cause death, myocardial infarction (MI), major stroke, and reintervention
  • Major Adverse Events (MAE) [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
  • Conduction disturbance requiring permanent pacemaker implantation [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
  • Change in NYHA class from baseline [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: No ]
  • Change in distance walked during 6-minute walk test (6MWT) from baseline [ Time Frame: 30 days and 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 from baseline [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: No ]
    Kansas City Cardiomyopathy Questionnaire (KCCQ), SF-12, and EuroQoL
  • Echocardiographic assessment of prosthetic valve performance [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    Measured by transvalvular mean gradient, effective orifice area, degree of aortic valve regurgitation (transvalvular and paravalvular)
  • Repeat hospitalization [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: No ]
  • Cardiovascular deaths and valve-related deaths [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
  • Strokes (of any severity) and TIAs [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
  • Index procedure related MAEs [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Medtronic CoreValve® System and SAVR subjects only
  • Length of index procedure hospital stay [ Designated as safety issue: No ]
    Medtronic CoreValve® System and SAVR subjects only
  • Device success [ Designated as safety issue: Yes ]
    Medtronic CoreValve® System subjects only
  • Procedural success [ Designated as safety issue: No ]
    Device success and absence of in-hospital MACCE
  • Evidence of prosthetic valve dysfunction [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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
Medtronic CoreValve® U.S. Pivotal Trial

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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Severe Aortic Stenosis
  • Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
  • Device: Surgical Aortic Valve Replacement (SAVR)
  • Experimental: Medtronic CoreValve® System TAVI
    Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
    Intervention: 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)
    Intervention: 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
    Intervention: 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.
    Intervention: Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1650
August 2019
August 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Extreme Risk Only: Subject must have comorbidities 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 Only: Subject must have comorbidities 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.
  • 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
  • Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater.
  • 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.
  • The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

Exclusion Criteria:

Clinical

  • Evidence of an acute myocardial infarction ≤ 30 days before the intended treatment.
  • Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the intended treatment. (High Risk Surgical Only: Including bare metal stents. Additionally, any drug eluting stents placed within 6 months prior to the index procedure.)
  • Blood dyscrasias as defined: leukopenia (WBC < 1000mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy.
  • Untreated clinically significant coronary artery disease requiring revascularization.
  • Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
  • Need for emergency surgery for any reason.
  • Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% as measured by resting echocardiogram.
  • Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
  • End stage renal disease requiring chronic dialysis or creatinine clearance < 20 cc/min.
  • Active Gastrointestinal (GI) bleeding within the past 3 months.
  • A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated:
  • Aspirin
  • Heparin (HIT/HITTS)
  • Bivalirudin (Extreme Risk Only)
  • Nitinol (titanium or nickel)
  • Ticlopidine and clopidogrel
  • Contrast media
  • Ongoing sepsis, including active endocarditis.
  • Subject refuses a blood transfusion.
  • Life expectancy < 12 months due to associated non-cardiac co-morbid conditions.
  • Other medical, social, or psychological conditions that in the opinion of an Investigator precludes the subject from appropriate consent.
  • 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).
  • Currently participating in an investigational drug or another device trial.
  • Symptomatic carotid or vertebral artery disease.
  • Subject has been offered surgical aortic valve replacement but declined. (High Risk Surgical Only)

Anatomical

  • Native aortic annulus size < 18 mm or > 29 mm per the baseline diagnostic imaging.
  • Pre-existing prosthetic heart valve any position.
  • Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation (3-4+)).
  • Moderate to severe (3-4+) or severe (4+) mitral or severe (4+) tricuspid regurgitation.
  • Moderate to severe mitral stenosis.
  • Hypertrophic obstructive cardiomyopathy.
  • New or untreated echocardiographic evidence of intracardiac mass, thrombus or vegetation.
  • Severe basal septal hypertrophy with an outflow gradient.
  • 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).
  • 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.
  • Congenital bicuspid or unicuspid valve verified by echocardiography.
  • Sinus of valsalva anatomy that would prevent adequate coronary perfusion.

Vascular

- Transarterial access not able to accommodate an 18Fr sheath.

Both
Not Provided
No
Contact: Joleen Perkins RS.CSTechSupport@medtronic.com
United States
 
NCT01240902
MCV-US-2009-01
Yes
Medtronic Cardiovascular
Medtronic Cardiovascular
Not Provided
Principal Investigator: David H Adams, MD Mount Sinai School of Medicine
Principal Investigator: Jeffrey J Popma, MD Beth Israel Deaconess Medical Center
Medtronic Cardiovascular
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP