Safety & Efficacy Study of the Medtronic CoreValve® System-Treatment of Symptomatic Severe Aortic Stenosis With Significant Comorbidities in Extreme Risk Subjects Who Need Aortic Valve Replacement

NCT ID: NCT01675440

Last Updated: 2025-10-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 782 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2026-01-31

Brief Summary

To evaluate the safety and efficacy of the Medtronic CoreValve® System for the treatment of symptomatic severe aortic stenosis in subjects with significant comorbidities in whom the risk of surgical aortic valve replacement has a predicted operative mortality or serious, irreversible morbidity risk of ≥50% at 30 days.

Detailed Description

The primary objective of the study is to evaluate the safety and effectiveness of the Medtronic CoreValve® System (MCS) in a subset of subjects excluded from the U.S. Extreme Risk Pivotal Trial population due to one or more additional co-morbidities, as measured by a composite of all-cause death or major stroke at 12 months, in the treatment of symptomatic severe aortic stenosis in subjects necessitating aortic valve replacement. Subjects enrolled in this study have a predicted operative mortality or serious, irreversible morbidity risk of ≥50% at 30 days associated with surgical aortic valve replacement.

Conditions

Severe Aortic Stenosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Severe (≥3-4+) Mitral Valve Regurgitation

Mitral valve regurgitation ≥3-4+

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type: DEVICE

Severe (≥3-4+) Tricuspid Valve Regurgitation

Tricuspid valve regurgitation ≥3-4+

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type: DEVICE

End Stage Renal Disease (ESRD)

End stage renal disease requiring renal replacement therapy or a creatinine clearance (CRCL) \<20 cc/min, but not on dialysis

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type: DEVICE

Low Gradient Low Output Aortic Stenosis

Low gradient low output aortic stenosis

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type: DEVICE

Failed Bioprosthetic Surgical Aortic Valve

Stenosed, insufficient or combined bioprosthetic surgical aortic valve failure

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type: DEVICE

2 or More Conditions

2 or more of the listed conditions

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type: DEVICE

Interventions

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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.
• Subjects must meet all of the criteria under at least one of the sub-groups 2a-c:

a. Senile degenerative aortic valve stenosis and i. At least one of the following co-morbid conditions:

1. Severe (≥3-4+) mitral valve regurgitation as measured by echocardiography

2. Severe (≥3-4+) tricuspid valve regurgitation as measured by echocardiography

3. End-stage renal disease requiring renal replacement therapy (Stage 5 of the KDOQI CKD Classification) or creatinine clearance <20cc/min but not requiring renal replacement therapy

AND

ii. mean gradient > 40 mmHg or jet velocity greater than 4.0 m/sec by either resting or dobutamine stress echocardiogram (if the LVEF < 50%), or simultaneous pressure recordings at cardiac catheterization either resting or with dobutamine stress (if the LVEF < 50%) AND iii. 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

AND/OR

b. Low gradient, low output aortic stenosis as defined by the presence of all three of the following i. In the presence of LVEF <50%, absence of contractile reserve, a mean gradient ≥25mmHg and <40mmHg AND jet velocity less than 4.0m/sec with dobutamine stress echocardiography or simultaneous pressure recordings at cardiac catheterization OR In the presence of LVEF ≥50%, a mean gradient ≥25mmHg and <40mmHg AND jet velocity less than 4.0 m/sec, by echocardiography or simultaneous pressure recordings at cardiac catheterization AND ii. 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 AND iii. radiographic evidence of severe aortic valve calcification AND/OR c. Failed bioprosthetic surgical aortic valve

• 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 study, 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 MCS TAVI procedure.
• Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the MCS TAVI 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).
• Active Gastrointestinal (GI) bleeding that would preclude anticoagulation.
• A known hypersensitivity or contraindication to all anticoagulation/antiplatelet regimens (including ability to be anticoagulated for the index procedure), nitinol, or [allergic] sensitivity to contrast media which cannot be adequately pre-medicated.
• 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 study/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 study.
• Symptomatic carotid or vertebral artery disease.

Anatomical

Subject has a:

• Native aortic annulus size <18 mm or >29 mm per the baseline diagnostic imaging (not applicable for TAV in SAV subjects) OR
• Surgical bioprosthetic annulus <17mm or >29mm i. Stented SAV per the manufactured labeled inner diameter OR ii. Stentless SAV per the baseline diagnostic imaging
• Subject has a pre-existing prosthetic heart valve with a rigid support structure in either the mitral or pulmonic position:

1. that could affect the implantation or function of the study valve OR

2. the implantation of the study valve could affect the function of the pre-existing prosthetic heart valve

• Moderate to severe mitral stenosis.
• Mixed aortic valve disease: aortic stenosis and aortic regurgitation with predominant aortic regurgitation, (AR is moderate-severe to severe (≥3-4+))(except for failed surgical bioprothesis)
• Hypertrophic obstructive cardiomyopathy.
• Echocardiographic evidence of new or untreated 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 that exceeds the maximum diameter for any given native or surgical bioprosthetic* aortic annulus size (see table below) Aortic Annulus Diameter/ Ascending Aorta Diameter, 18 mm* - 20 mm/ >34 mm, 20 mm - 23 mm/ >40 mm, 23 mm - 27 mm/ >43 mm, 27 mm - 29 mm/ >43 mm,

• 17mm for surgical bioprosthetic aortic annulus
• Congenital bicuspid or unicuspid valve verified by echocardiography (Not applicable for TAV in SAV subjects).
• Sinus of valsalva anatomy that would prevent adequate coronary perfusion.
• Degenerated surgical bioprothesis presents with a significant concomitant perivalvular leak (between prothesis and native annulus), is not securely fixed in the native annulus, or is not structurally intact (e.g. wireform frame fracture) (ONLY FOR TAV in SAV subjects)
• Degenerated surgical bioprothesis presents with a partially detached leaflet that in the aortic position may obstruct a coronary ostium (ONLY FOR TAV in SAV subjects)

Vascular

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medtronic Cardiovascular

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David H Adams

Role: PRINCIPAL_INVESTIGATOR

Mount Sinai Health System

Locations

Banner Good Samaritan

Phoenix, Arizona, United States

Kaiser Permanente - Los Angeles Medical Center

Los Angeles, California, United States

University of Southern California University Hospital

Los Angeles, California, United States

VA Palo Alto Health Care System

Palo Alto, California, United States

Hartford Hospital

Hartford, Connecticut, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Washington Hospital Center / Georgetown Hospital

Washington D.C., District of Columbia, United States

University of Miami Health System / Jackson Memorial Hospital

Miami, Florida, United States

Mount Sinai Medical Center

Miami Beach, Florida, United States

Piedmont Heart Institute

Atlanta, Georgia, United States

Saint Joseph's Hospital of Atlanta

Atlanta, Georgia, United States

Loyola University Medical Center

Maywood, Illinois, United States

St. Vincent Heart Center of Indiana

Indianapolis, Indiana, United States

Iowa Heart Center

Des Moines, Iowa, United States

University of Kansas Hospital

Kansas City, Kansas, United States

Cardiovascular Institute of the South/Terrebonne General

Houma, Louisiana, United States

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Michigan Health Systems

Ann Arbor, Michigan, United States

Detroit Medical Center Cardiovascular Institute

Detroit, Michigan, United States

St. John Hospital and Medical Center

Detroit, Michigan, United States

Spectrum Health Hospitals

Grand Rapids, Michigan, United States

Morristown Memorial Hospital

Morristown, New Jersey, United States

North Shore University Hospital

Manhasset, New York, United States

NYU Langone Medical Center

New York, New York, United States

The Mount Sinai Medical Center

New York, New York, United States

Lenox Hill Hospital

New York, New York, United States

St. Francis Hospital

Roslyn, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University - Baptist Medical Center

Winston-Salem, North Carolina, United States

University Hospitals - Case Medical Center

Cleveland, Ohio, United States

The Ohio State University Medical Center - The Richard M. Ross Heart Hospital

Columbus, Ohio, United States

Riverside Methodist Hospital

Columbus, Ohio, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Pinnacle Health

Wormleysburg, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor Heart and Vascular Hospital

Dallas, Texas, United States

Texas Heart Institute at St. Luke's Episcopal Hospital

Houston, Texas, United States

The Methodist Hospital - The Methodist DeBakey Heart & Vascular Center

Houston, Texas, United States

University of Vermont Medical Center

Burlington, Vermont, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

St. Luke's Medical Center - Aurora Health Care

Milwaukee, Wisconsin, United States

Countries

United States

References

Butala NM, Song Y, Shen C, Cohen DJ, Yeh RW. Effect of intensive versus limited monitoring on clinical trial conduct and outcomes: A randomized trial. Am Heart J. 2022 Jan;243:77-86. doi: 10.1016/j.ahj.2021.09.002. Epub 2021 Sep 14.

Reference Type: DERIVED

PMID: 34529944 (View on PubMed)

Dauerman HL, Deeb GM, O'Hair DP, Waksman R, Yakubov SJ, Kleiman NS, Chetcuti SJ, Hermiller JB Jr, Bajwa T, Khabbaz K, de Marchena E, Salerno T, Dries-Devlin JL, Li S, Popma JJ, Reardon MJ. Durability and Clinical Outcomes of Transcatheter Aortic Valve Replacement for Failed Surgical Bioprostheses. Circ Cardiovasc Interv. 2019 Oct;12(10):e008155. doi: 10.1161/CIRCINTERVENTIONS.119.008155. Epub 2019 Oct 14.

Reference Type: DERIVED

PMID: 31607151 (View on PubMed)

Other Identifiers

10050361DOC

Identifier Type: -

Identifier Source: org_study_id