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

October 21, 2022 updated by: Medtronic Cardiovascular

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1453

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Banner Good Samaritan
    • California
      • Los Angeles, California, United States, 90033
        • University of Southern California University Hospital
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente - Los Angeles Medical Center
      • Mountain View, California, United States, 94040
        • El Camino Hospital
      • Palo Alto, California, United States, 94304
        • VA Palo Alto Health Care System
    • Connecticut
      • Hartford, Connecticut, United States, 06102
        • Hartford Hospital
      • New Haven, Connecticut, United States, 06520
        • Yale New Haven Hospital
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Washington Hospital Center / Georgetown Hospital
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Health System / Jackson Memorial Hospital
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Saint Joseph's Hospital of Atlanta
      • Atlanta, Georgia, United States, 30309
        • Piedmont Heart Institute
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46290
        • St. Vincent Heart Center of Indiana
    • Iowa
      • Des Moines, Iowa, United States, 50314
        • Iowa Heart Center
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Hospital
    • Louisiana
      • Houma, Louisiana, United States, 70360
        • Cardiovascular Institute of the South/ Terrebone General
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health Systems
      • Detroit, Michigan, United States, 48236
        • St. John Hospital and Medical Center
      • Detroit, Michigan, United States, 48201
        • Detroit Medical Center Cardiovascular Institute
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health Hospitals
    • New Jersey
      • Morristown, New Jersey, United States, 07962
        • Morristown Memorial Hospital
    • New York
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital/ Long Island Jewish Hospital
      • New York, New York, United States, 10016
        • NYU Langone Medical Center
      • New York, New York, United States, 10029
        • The Mount Sinai Medical Center
      • New York, New York, United States, 10075
        • Lenox Hill Hospital
      • Roslyn, New York, United States, 11576
        • St. Francis Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University - Baptist Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals - Case Medical Center
      • Columbus, Ohio, United States, 43214
        • Riverside Methodist Hospital
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center - The Richard M. Ross Heart Hospital
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Harrisburg, Pennsylvania, United States, 17043
        • Pinnacle Health
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75226
        • Baylor Heart and Vascular Hospital
      • Houston, Texas, United States, 77030
        • Texas Heart Institute at St. Luke's Episcopal Hospital
      • Houston, Texas, United States, 77030
        • The Methodist Hospital - The Methodist DeBakey Heart & Vascular Center
    • Vermont
      • Burlington, Vermont, United States, 05458
        • University of Vermont Medical Center
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
    • Washington
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • St. Luke's Medical Center - Aurora Health Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)
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)
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)
Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Active Comparator: High Risk: SAVR
High Risk Surgical Patients: Surgical Aortic Valve Replacement (SAVR)
Device: Surgical Aortic Valve Replacement (SAVR)
Surgical Aortic Valve Replacement (SAVR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality
Time Frame: 1 year
All-cause Death or Major Stroke (Extreme Risk- Medtronic CoreValve® System); All-cause Mortality (High Risk Surgical- Medtronic CoreValve® System vs. Surgical Valve)
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
Time Frame: 30 day, 6 month, 1 year, 2 year

MACCE is defined as a composite of:

  • All Cause Mortality
  • Myocardial infarction (MI)
  • All Stroke
  • Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)
30 day, 6 month, 1 year, 2 year
The Occurrence of Individual MACCE Components
Time Frame: 30 day, 6 month, 1 year, 2 year

Individual MACCE Components Include:

  • All Cause Mortality
  • MI
  • All stroke
  • Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)
30 day, 6 month, 1 year, 2 year
Major Adverse Events (MAEs)
Time Frame: 30 day, 6 month, 1 year, 2 year

MAEs Include:

  • MACCE
  • Acute Kidney Injury
  • Cardiac Tamponade
  • Prosthetic Valve Dysfunction
  • Cardiogenic Shock
  • Valve Endocarditis
  • Life-Threatening, Disabling or Major Bleeding
  • Major Vascular Complication
  • Cardiac Perforation
  • Device Migration/Valve Embolism
30 day, 6 month, 1 year, 2 year
Conduction Disturbance Requiring Permanent Pacemaker Implantation
Time Frame: 30 day, 6 month, 1 year, 2 year
30 day, 6 month, 1 year, 2 year
Change in NYHA Class
Time Frame: 30 day, 6 month, 1 year, 2 year

Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.

New York Heart Association (NYHA) Classification:

Class I: Subjects with cardiac disease but without resulting limitations of physical activity.

Class I: Subjects with cardiac disease resulting in slight limitation of physical activity.

Class III: Subjects with cardiac disease resulting in marked limitation of physical activity.

Class IV: Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort.
30 day, 6 month, 1 year, 2 year
Change in Distance Walked During 6-Minute Walk Test (6MWT)
Time Frame: 30 day, 1 year
Change in distance walked during 6MWT from baseline
30 day, 1 year
Ratio of Days Alive Out of Hospital Versus Total Days Alive
Time Frame: 1 year
1 year
Quality of Life (QoL) Change
Time Frame: 30 day, 6 month, 1 year, 2 year

QoL summary score change from baseline using the following measures:

  • Kansas City Cardiomyopathy Questionnaire (KCCQ): Quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
  • 12 Item Short Form Health Survey (SF-12): Measures functional health and well-being. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
  • European QoL (EQ-5D): Measures 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that can be converted to utilities using an algorithm. Utilities range from 0 to 1, with 1 representing perfect health, and 0 corresponding to the worst imaginable health state.
30 day, 6 month, 1 year, 2 year
Echocardiographic Assessment of Valve Performance
Time Frame: 30 day, 6 month, 1 year, 2 year

Using the following measures:

- Effective Orifice Area (EOA)
30 day, 6 month, 1 year, 2 year
Echocardiographic Assessment of Valve Performance
Time Frame: 30 day, 6 month, 1 year, 2 year

Using the following measures:

- Transvalvular Mean Gradient
30 day, 6 month, 1 year, 2 year
Echocardiographic Assessment of Valve Performance
Time Frame: 30 day, 6 month, 1 year, 2 year

Using the following measure:

- Degree of Aortic Valve Regurgitation (Transvalvular and Paravalvular)
30 day, 6 month, 1 year, 2 year
Aortic Valve Hospitalizations
Time Frame: 30 day, 6 month, 1 year, 2 year
30 day, 6 month, 1 year, 2 year
Cardiovascular Deaths and Valve Related Deaths
Time Frame: 30 day, 6 month, 1 year, 2 year
30 day, 6 month, 1 year, 2 year
Strokes and Transient Ischemic Attacks (TIAs)
Time Frame: 30 day, 6 month, 1 year, 2 year
Strokes (of any severity) and TIAs
30 day, 6 month, 1 year, 2 year
Index Procedure Related MAEs
Time Frame: Procedure
Procedure
Length of Index Procedure Hospital Stay
Time Frame: Number of days from admission to discharge
Number of days from admission to discharge
Device Success
Time Frame: Number of days from admission to discharge

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
Number of days from admission to discharge
Procedural Success
Time Frame: Number of days from admission to discharge

Medtronic CoreValve® System subjects only.

Defined as device success and absence of in-hospital MACCE.
Number of days from admission to discharge
Prosthetic Valve Dysfunction (PVD)
Time Frame: 30 day, 6 month, 1 year, 2 year

PVD was defined according to VARC I using the Core Lab Echocardiography assessments including aortic regurgitation (AR) and aortic stenosis (AS) evaluations. Total AR reported as moderate or severe was considered PVD. AS was defined as significant stenosis and considered PVD if one of the following was met:

  • Peak velocity >4 m/s
  • Mean gradient >35 mmHg
  • EOA < 0.8 cm2
  • TVIV1 / TVIV2 < 0.25
30 day, 6 month, 1 year, 2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medtronic Cardiovascular

Investigators

  • Principal Investigator: David H Adams, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 10, 2010

Primary Completion (Actual)

August 1, 2014

Study Completion (Actual)

May 15, 2019

Study Registration Dates

First Submitted

November 10, 2010

First Submitted That Met QC Criteria

November 12, 2010

First Posted (Estimate)

November 15, 2010

Study Record Updates

Last Update Posted (Actual)

October 25, 2022

Last Update Submitted That Met QC Criteria

October 21, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCV-US-2009-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Severe Aortic Stenosis

Clinical Trials on Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Estonia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe