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 ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Medtronic Cardiovascular
ClinicalTrials.gov Identifier:
NCT01240902
First received: November 10, 2010
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 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 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)


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, 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.


Estimated Enrollment: 1650
Study Start Date: November 2010
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2015 (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)

  Eligibility

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

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.

  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: NCT01240902

  Hide Study Locations
Locations
United States, Arizona
Banner Good Samaritan
Phoenix, Arizona, United States, 85006
United States, California
Kaiser Permanente - Los Angeles Medical Center
Los Angeles, California, United States, 90027
University of Southern California University Hospital
Los Angeles, California, United States, 90033
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
University of Miami Health System / Jackson Memorial Hospital
Miami, Florida, United States, 33136
Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
United States, Georgia
Saint Joseph's Hospital of Atlanta
Atlanta, Georgia, United States, 30342
Piedmont Heart Institute
Atlanta, Georgia, United States, 30309
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/ Terrebone 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
St. John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Detroit Medical Center Cardiovascular Institute
Detroit, Michigan, United States, 48201
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
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
The Ohio State University Medical Center - The Richard M. Ross Heart Hospital
Columbus, Ohio, United States, 43210
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
Investigators
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 by Medtronic Cardiovascular

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Medtronic Cardiovascular
ClinicalTrials.gov Identifier: NCT01240902     History of Changes
Other Study ID Numbers: MCV-US-2009-01
Study First Received: November 10, 2010
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
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 October 16, 2014