Clinical trial NCT01531374: 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
Official title: Medtronic CoreValve® Continued Access Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Aortic Stenosis
Keywords: Valvular Heart Disease
Critical Aortic Stenosis
Severe Aortic Stenosis
Extreme Risk
High Risk
Aortic Valve Replacement
Lead sponsor: Medtronic Cardiovascular
Sponsor class: INDUSTRY
First posted: 2012-02-10
Enrollment: 2777
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality
timeFrame: 1 year
Secondary outcomes:
measure: Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: The Occurrence of Individual MACCE Components
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Major Adverse Events (MAEs)
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Conduction Disturbance Requiring Permanent Pacemaker Implantation
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Change From Baseline in NYHA Class
timeFrame: Baseline to 30 days, baseline to 6 months, baseline to 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Change From Baseline in Distance Walked During 6-Minute Walk Test (6MWT)
timeFrame: Baseline to 30 days, baseline to 1 year
measure: Ratio of Days Alive Out of Hospital at 365 Days Post Procedure Versus Total Days Alive
timeFrame: 1 year
measure: Quality of Life (QoL) Change
timeFrame: 30 day, 6 month, 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Echocardiographic Assessment of Valve Performance
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Echocardiographic Assessment of Valve Performance
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Echocardiographic Assessment of Valve Performance
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Aortic Valve Hospitalizations
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Cardiovascular Deaths and Valve-Related Deaths
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Strokes and Transient Ischemic Attacks (TIAs)
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
measure: Index Procedure Related MAEs
timeFrame: Procedure
measure: Length of Index Procedure Hospital Stay
timeFrame: Number of days from admission to discharge
measure: Device Success
timeFrame: Number of days from admission to discharge
measure: Procedural Success
timeFrame: Number of days from admission to discharge
measure: Prosthetic Valve Dysfunction (PVD)
timeFrame: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Good Samaritan
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California University Hospital
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente - Los Angeles Medical Center
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center / Georgetown Hospital
state: District of Columbia
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami Health System / Jackson Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Atlanta
country: United States
facility: Saint Joseph's Hospital of Atlanta
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Heart Center of Indiana
state: Indiana
city: Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Houma
country: United States
facility: Cardiovascular Institute of the South/Terrebonne General
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
city: Detroit
country: United States
facility: Detroit Medical Center Cardiovascular Institute
state: Michigan
city: Detroit
country: United States
facility: St. John Hospital and Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals
state: Michigan
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Manhasset
country: United States
facility: North Shore University Hospital/ Long Island Jewish Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: The Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University - Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals - Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center - The Richard M. Ross Heart Hospital
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Harrisburg
country: United States
facility: Pinnacle Health
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Heart and Vascular Hospital
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute at St. Luke's Episcopal Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital - The Methodist DeBakey Heart & Vascular Center
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center
state: Washington
city: Milwaukee
country: United States
facility: St. Luke's Medical Center - Aurora Health Care
state: Wisconsin
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: David H Adams, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.