Severe Aortic StenosisNCT01675440
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
An observational study of Severe Aortic Stenosis, run by Medtronic Cardiovascular at 43 sites in United States.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Severe Aortic Stenosis
- What is being tested?
- Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
- Type of treatment
- Medical device
- How many people
- 782 participants
- Where
- 43 sitesUnited States
- Study dates
- Aug 2012to 8 Apr 2025
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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)
Who may be able to join
- 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:
- Senile degenerative aortic valve stenosis and i. At least one of the following co-morbid conditions:
- Severe (≥3-4+) mitral valve regurgitation as measured by echocardiography
- Severe (≥3-4+) tricuspid valve regurgitation as measured by echocardiography
- 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
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- AND
- 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
- 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.
Who cannot join
- 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.
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- 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:
- that could affect the implantation or function of the study valve OR
- 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.
Trial locations and contacts
43 sites in 1 country.
43 sites in 1 country
United States43 sites
University of Michigan Health Systems
Ann Arbor, Michigan, 48109
Piedmont Heart Institute
Atlanta, Georgia, 30309
Saint Joseph's Hospital of Atlanta
Atlanta, Georgia, 30342
The Johns Hopkins Hospital
Baltimore, Maryland, 21287
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
University of Vermont Medical Center
Burlington, Vermont, 05458
University Hospitals - Case Medical Center
Cleveland, Ohio, 44106
The Ohio State University Medical Center - The Richard M. Ross Heart Hospital
Columbus, Ohio, 43210
Riverside Methodist Hospital
Columbus, Ohio, 43214
Baylor Heart and Vascular Hospital
Dallas, Texas, 75226
Geisinger Medical Center
Danville, Pennsylvania, 17822
Iowa Heart Center
Des Moines, Iowa, 50314
Detroit Medical Center Cardiovascular Institute
Detroit, Michigan, 48201
St. John Hospital and Medical Center
Detroit, Michigan, 48236
Duke University Medical Center
Durham, North Carolina, 27710
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Spectrum Health Hospitals
Grand Rapids, Michigan, 49503
Hartford Hospital
Hartford, Connecticut, 06102
Cardiovascular Institute of the South/Terrebonne General
Houma, Louisiana, 70360
Texas Heart Institute at St. Luke's Episcopal Hospital
Houston, Texas, 77030
The Methodist Hospital - The Methodist DeBakey Heart & Vascular Center
Houston, Texas, 77030
St. Vincent Heart Center of Indiana
Indianapolis, Indiana, 46290-1090
University of Kansas Hospital
Kansas City, Kansas, 66160
Kaiser Permanente - Los Angeles Medical Center
Los Angeles, California, 90027
University of Southern California University Hospital
Los Angeles, California, 90033
North Shore University Hospital
Manhasset, New York, 11030
Loyola University Medical Center
Maywood, Illinois, 60153
University of Miami Health System / Jackson Memorial Hospital
Miami, Florida, 33136
Mount Sinai Medical Center
Miami Beach, Florida, 10029
St. Luke's Medical Center - Aurora Health Care
Milwaukee, Wisconsin, 53215
Morristown Memorial Hospital
Morristown, New Jersey, 07962
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Yale New Haven Hospital
New Haven, Connecticut, 06520
NYU Langone Medical Center
New York, New York, 10016
The Mount Sinai Medical Center
New York, New York, 10029
Lenox Hill Hospital
New York, New York, 10075
VA Palo Alto Health Care System
Palo Alto, California, 94304
Banner Good Samaritan
Phoenix, Arizona, 85006
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
St. Francis Hospital
Roslyn, New York, 11576
Washington Hospital Center / Georgetown Hospital
Washington D.C., District of Columbia, 20010
Wake Forest University - Baptist Medical Center
Winston-Salem, North Carolina, 27157
Pinnacle Health
Wormleysburg, Pennsylvania, 17101
About this study
Official title: Medtronic CoreValve® U.S. Expanded Use Study
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.
Read the 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
- Being tested
- Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)Device
| Study group | Role | What they receive |
|---|---|---|
| Severe (≥3-4+) Mitral Valve Regurgitation | Mitral valve regurgitation ≥3-4+ Receives: Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) | |
| Severe (≥3-4+) Tricuspid Valve Regurgitation | Tricuspid valve regurgitation ≥3-4+ Receives: Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) | |
| 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 Receives: Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) | |
| Low Gradient Low Output Aortic Stenosis | Low gradient low output aortic stenosis Receives: Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) | |
| Failed Bioprosthetic Surgical Aortic Valve | Stenosed, insufficient or combined bioprosthetic surgical aortic valve failure Receives: Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) | |
| 2 or More Conditions | 2 or more of the listed conditions Receives: Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause Mortality or Major stroke
All-cause Mortality or Major Stroke
Measured: 12 months
Secondary outcomes (17)
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)
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
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)
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
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
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
Conduction Disturbance Requiring Permanent Pacemaker Implantation
The incidence of conduction disturbance requiring permanent pacemaker implantation
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
Change in NYHA Class
Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
Change in Distance Walked During 6-minute Walk Test (6MWT) from Baseline
Change in distance walked during 6MWT from baseline
Measured: 30 days and 12 months
Ratio of Days Alive Out of Hospital Versus Total Days Alive
Measured: 12 months
Quality of Life (QoL) Change from Baseline
QoL change from baseline using the following measures: •Kansas City Cardiomyopathy Questionnaire (KCCQ) •SF-12 •EuroQoL
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
Echocardiographic Assessment of Valve Performance
Using the following measures: • Transvalvular mean gradient • Effective orifice area (EOA) •degree of aortic valve regurgitation
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
Aortic Valve Disease Hospitalization
The number of subjects re-hospitalized after the initial procedure
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
Cardiovascular Deaths and Valve-related Deaths
The number of cardiovascular deaths and valve-related deaths
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
Strokes
The number of subjects with strokes and TIAs
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
Index Procedure Related Major Adverse Events (MAEs)
Index procedure-related MAE events will be summarized
Measured: Procedure
Length of Index Procedure Hospital Stay
The length of index procedure hospital stay will be summarized
Measured: Number of days from admission to discharge
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.
Measured: Number of days from admission to discharge
Procedural Success
Defined as device success and absence of in-hospital MACCE
Measured: Number of days from admission to discharge
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
Measured: 30 days, 6 months, 12 months and annually thereafter up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2012 (estimated)
- Study startAug 2012
- Primary completionDec 2016
- Study completion8 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Severe Aortic StenosisStudies of the same condition, open and under way.
- More trials run by Medtronic CardiovascularThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 782 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medtronic Cardiovascular
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David H Adams, Principal investigator, Mount Sinai Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01675440
- Sponsor's protocol ID
- 10050361DOC
- Status last verified
- May 2026
- First submitted
- 22 Aug 2012
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 34529944Dauerman 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.
PubMed 31607151