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

NCT ID: NCT01531374

Last Updated: 2022-10-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

2777 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-21

Study Completion Date

2019-11-18

Brief Summary

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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.

Detailed Description

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Conditions

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Severe Aortic Stenosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Extreme Risk: TAVI Iliofemoral

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Group Type EXPERIMENTAL

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type DEVICE

Extreme Risk: TAVI Non-Iliofemoral

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Group Type EXPERIMENTAL

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type DEVICE

High Risk: TAVI

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Group Type EXPERIMENTAL

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type DEVICE

Interventions

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Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Intervention Type DEVICE

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medtronic Cardiovascular

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David H Adams, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

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Banner Good Samaritan

Phoenix, Arizona, United States

Site Status

University of Southern California University Hospital

Los Angeles, California, United States

Site Status

Kaiser Permanente - Los Angeles Medical Center

Los Angeles, California, United States

Site Status

El Camino Hospital

Mountain View, California, United States

Site Status

VA Palo Alto Health Care System

Palo Alto, California, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

Washington Hospital Center / Georgetown Hospital

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

Site Status

University of Miami Health System / Jackson Memorial Hospital

Miami, Florida, United States

Site Status

Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Piedmont Heart Institute

Atlanta, Georgia, United States

Site Status

Saint Joseph's Hospital of Atlanta

Atlanta, Georgia, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

St. Vincent Heart Center of Indiana

Indianapolis, Indiana, United States

Site Status

Iowa Heart Center

Des Moines, Iowa, United States

Site Status

University of Kansas Hospital

Kansas City, Kansas, United States

Site Status

Cardiovascular Institute of the South/Terrebonne General

Houma, Louisiana, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Health Systems

Ann Arbor, Michigan, United States

Site Status

Detroit Medical Center Cardiovascular Institute

Detroit, Michigan, United States

Site Status

St. John Hospital and Medical Center

Detroit, Michigan, United States

Site Status

Spectrum Health Hospitals

Grand Rapids, Michigan, United States

Site Status

Morristown Memorial Hospital

Morristown, New Jersey, United States

Site Status

North Shore University Hospital/ Long Island Jewish Hospital

Manhasset, New York, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

The Mount Sinai Medical Center

New York, New York, United States

Site Status

Lenox Hill Hospital

New York, New York, United States

Site Status

St. Francis Hospital

Roslyn, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest University - Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

University Hospitals - Case Medical Center

Cleveland, Ohio, United States

Site Status

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

Columbus, Ohio, United States

Site Status

Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Pinnacle Health

Harrisburg, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Baylor Heart and Vascular Hospital

Dallas, Texas, United States

Site Status

Texas Heart Institute at St. Luke's Episcopal Hospital

Houston, Texas, United States

Site Status

The Methodist Hospital - The Methodist DeBakey Heart & Vascular Center

Houston, Texas, United States

Site Status

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Providence Sacred Heart Medical Center

Spokane, Washington, United States

Site Status

St. Luke's Medical Center - Aurora Health Care

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Yakubov SJ, Van Mieghem NM, Oh JK, Ito S, Grubb KJ, O'Hair D, Forrest JK, Gada H, Mumtaz M, Deeb GM, Tang GHL, Rovin JD, Jain R, Windecker S, Skelding KA, Kleiman NS, Chetcuti SJ, Dedrick A, Boatman SV, Popma JJ, Reardon MJ. Impact of Transcatheter or Surgical Aortic Valve Performance on 5-Year Outcomes in Patients at >/= Intermediate Risk. J Am Coll Cardiol. 2025 Apr 8;85(13):1419-1430. doi: 10.1016/j.jacc.2025.02.009. Epub 2025 Mar 9.

Reference Type DERIVED
PMID: 40175015 (View on PubMed)

Klautz RJM, Rao V, Reardon MJ, Deeb GM, Dagenais F, Moront MG, Little SH, Labrousse L, Patel HJ, Ito S, Li S, Sabik JF 3rd, Oh JK. Examining the typical hemodynamic performance of nearly 3000 modern surgical aortic bioprostheses. Eur J Cardiothorac Surg. 2024 May 3;65(5):ezae122. doi: 10.1093/ejcts/ezae122.

Reference Type DERIVED
PMID: 38710669 (View on PubMed)

O'Hair D, Yakubov SJ, Grubb KJ, Oh JK, Ito S, Deeb GM, Van Mieghem NM, Adams DH, Bajwa T, Kleiman NS, Chetcuti S, Sondergaard L, Gada H, Mumtaz M, Heiser J, Merhi WM, Petrossian G, Robinson N, Tang GHL, Rovin JD, Little SH, Jain R, Verdoliva S, Hanson T, Li S, Popma JJ, Reardon MJ. Structural Valve Deterioration After Self-Expanding Transcatheter or Surgical Aortic Valve Implantation in Patients at Intermediate or High Risk. JAMA Cardiol. 2023 Feb 1;8(2):111-119. doi: 10.1001/jamacardio.2022.4627.

Reference Type DERIVED
PMID: 36515976 (View on PubMed)

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)

Pineda AM, Kevin Harrison J, Kleiman NS, Reardon MJ, Conte JV, O'Hair DP, Chetcuti SJ, Huang J, Yakubov SJ, Popma JJ, Beohar N. Clinical impact of baseline chronic kidney disease in patients undergoing transcatheter or surgical aortic valve replacement. Catheter Cardiovasc Interv. 2019 Mar 1;93(4):740-748. doi: 10.1002/ccd.27928. Epub 2018 Oct 20.

Reference Type DERIVED
PMID: 30341970 (View on PubMed)

Kleiman NS, Maini BJ, Reardon MJ, Conte J, Katz S, Rajagopal V, Kauten J, Hartman A, McKay R, Hagberg R, Huang J, Popma J; CoreValve Investigators. Neurological Events Following Transcatheter Aortic Valve Replacement and Their Predictors: A Report From the CoreValve Trials. Circ Cardiovasc Interv. 2016 Sep;9(9):e003551. doi: 10.1161/CIRCINTERVENTIONS.115.003551.

Reference Type DERIVED
PMID: 27601429 (View on PubMed)

Other Identifiers

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10037989DOC REV 1C

Identifier Type: -

Identifier Source: org_study_id

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