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

Severe Aortic Stenosis Clinical Trial

Official title:

Medtronic CoreValve® U.S. Expanded Use Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01675440
• Other study ID #: 10050361DOC
• Status: Active, not recruiting
• Start date: August 2012
• Est. completion date: January 2026

Study information

• Verified date: October 2023
• Source: Medtronic Cardiovascular
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 782
• Est. completion date: January 2026
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic
• Severe Aortic Stenosis

Intervention

Device:
• Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Locations

Country	Name	City	State
United States	University of Michigan Health Systems	Ann Arbor	Michigan
United States	Piedmont Heart Institute	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	University of Vermont Medical Center	Burlington	Vermont
United States	University Hospitals - Case Medical Center	Cleveland	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Ohio State University Medical Center - The Richard M. Ross Heart Hospital	Columbus	Ohio
United States	Baylor Heart and Vascular Hospital	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Iowa Heart Center	Des Moines	Iowa
United States	Detroit Medical Center Cardiovascular Institute	Detroit	Michigan
United States	St. John Hospital and Medical Center	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Spectrum Health Hospitals	Grand Rapids	Michigan
United States	Hartford Hospital	Hartford	Connecticut
United States	Cardiovascular Institute of the South/Terrebonne General	Houma	Louisiana
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	St. Vincent Heart Center of Indiana	Indianapolis	Indiana
United States	University of Kansas Hospital	Kansas City	Kansas
United States	Kaiser Permanente - Los Angeles Medical Center	Los Angeles	California
United States	University of Southern California University Hospital	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Miami Health System / Jackson Memorial Hospital	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	St. Luke's Medical Center - Aurora Health Care	Milwaukee	Wisconsin
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Lenox Hill Hospital	New York	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	VA Palo Alto Health Care System	Palo Alto	California
United States	Banner Good Samaritan	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	St. Francis Hospital	Roslyn	New York
United States	Washington Hospital Center / Georgetown Hospital	Washington	District of Columbia
United States	Wake Forest University - Baptist Medical Center	Winston-Salem	North Carolina
United States	Pinnacle Health	Wormleysburg	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiovascular

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause Mortality or Major stroke	All-cause Mortality or Major Stroke	12 months
Secondary	Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) Event Rate	MACCE is defined as a composite of: • All-Cause Death • 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 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary	The Occurrence of individual MACCE Components	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 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary	Major Adverse Events (MAEs)	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 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary	Conduction Disturbance Requiring Permanent Pacemaker Implantation	The incidence of conduction disturbance requiring permanent pacemaker implantation	30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary	Change in NYHA Class	Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.	30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary	Change in Distance Walked During 6-minute Walk Test (6MWT) from Baseline	Change in distance walked during 6MWT from baseline	30 days and 12 months
Secondary	Ratio of Days Alive Out of Hospital Versus Total Days Alive		12 months
Secondary	Quality of Life (QoL) Change from Baseline	QoL change from baseline using the following measures: •Kansas City Cardiomyopathy Questionnaire (KCCQ) •SF-12 •EuroQoL	30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary	Echocardiographic Assessment of Valve Performance	Using the following measures: • Transvalvular mean gradient • Effective orifice area (EOA) •degree of aortic valve regurgitation	30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary	Aortic Valve Disease Hospitalization	The number of subjects re-hospitalized after the initial procedure	30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary	Cardiovascular Deaths and Valve-related Deaths	The number of cardiovascular deaths and valve-related deaths	30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary	Strokes	The number of subjects with strokes and TIAs	30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary	Index Procedure Related Major Adverse Events (MAEs)	Index procedure-related MAE events will be summarized	Procedure
Secondary	Length of Index Procedure Hospital Stay	The length of index procedure hospital stay will be summarized	Number of days from admission to discharge
Secondary	Device Success	Defined as: 1) Successful vascular access, delivery and deployment of the device, and successful retrieval of the delivery system, 2) Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function), 3) 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) 4) Only one valve implanted in the proper anatomical location. For TAV in SAV subjects, only # 1, 2 and 4 will be used to calculate device success.	Number of days from admission to discharge
Secondary	Procedural Success	Defined as device success and absence of in-hospital MACCE	Number of days from admission to discharge
Secondary	Evidence of Prosthetic Valve Dysfunction	PVD was defined according to VARC using the site reported 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 days, 6 months, 12 months and annually thereafter up to 5 years