Clinical trial NCT01675440: 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
Official title: Medtronic CoreValve® U.S. Expanded Use Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Severe Aortic Stenosis
Lead sponsor: Medtronic Cardiovascular
Sponsor class: INDUSTRY
First posted: 2012-08-30
Enrollment: 782
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects with symptomatic severe aortic stenosis requiring aortic valve replacement, with predicted operative mortality or serious, irreversible morbidity risk of ≥ 50% at 30 days, and at least one of the following conditions:

* Severe (≥3-4+) mitral valve regurgitation
* Severe (≥3-4+) tricuspid valve regurgitation
* End stage renal disease (ESRD) requiring renal replacement therapy or creatinine clearance \<20cc/min, but not requiring renal replacement therapy
* Low gradient, low output aortic stenosis
* Failed bioprosthetic surgical aortic valve
* 2 or more conditions (listed above)

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.

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.

Primary outcomes:
measure: All-cause Mortality or Major stroke
timeFrame: 12 months
Secondary outcomes:
measure: Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) Event Rate
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
measure: The Occurrence of individual MACCE Components
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
measure: Major Adverse Events (MAEs)
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
measure: Conduction Disturbance Requiring Permanent Pacemaker Implantation
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
measure: Change in NYHA Class
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
measure: Change in Distance Walked During 6-minute Walk Test (6MWT) from Baseline
timeFrame: 30 days and 12 months
measure: Ratio of Days Alive Out of Hospital Versus Total Days Alive
timeFrame: 12 months
measure: Quality of Life (QoL) Change from Baseline
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
measure: Echocardiographic Assessment of Valve Performance
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
measure: Aortic Valve Disease Hospitalization
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
measure: Cardiovascular Deaths and Valve-related Deaths
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
measure: Strokes
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
measure: Index Procedure Related Major Adverse Events (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: Evidence of Prosthetic Valve Dysfunction
timeFrame: 30 days, 6 months, 12 months and annually thereafter up to 5 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Good Samaritan
state: Arizona
city: Los Angeles
country: United States
facility: Kaiser Permanente - Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California University 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: The 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
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: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Wormleysburg
country: United States
facility: Pinnacle Health
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: Milwaukee
country: United States
facility: St. Luke's Medical Center - Aurora Health Care
state: Wisconsin
Study officials:
affiliation: Mount Sinai Health System
name: David H Adams
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: 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.