Severe Aortic StenosisNCT01531374
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
A study testing Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) in people with Severe Aortic Stenosis, run by Medtronic Cardiovascular at 45 sites in United States.
Trial 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. 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
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,777 participants
- Where
- 45 sitesUnited States
- Study dates
- 21 Feb 2012to 18 Nov 2019
- Phase
- Interventional
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
Who may be able to join
- 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.
- 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
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- 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 trial, 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 intended treatment.
- Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the MCS TAVI procedure including bare metal and drug eluting stents.
- 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).
- End stage renal disease requiring chronic dialysis or creatinine clearance < 20 cc/min.
- Active GI bleeding that would preclude anticoagulation.
- 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
- 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 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).
- Currently participating in an investigational drug or another device trial.
- Symptomatic carotid or vertebral artery disease.
- Anatomical
- 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)
- Pre-existing prosthetic heart valve any position.
- Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation (3-4+)).
- Moderate to severe (3-4+) or severe (4+) mitral or severe (4+) tricuspid regurgitation.
- Moderate to severe mitral stenosis.
- 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 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).
- Congenital bicuspid or unicuspid valve verified by echocardiography.
- Sinus of valsalva anatomy that would prevent adequate coronary perfusion.
- Vascular
- Transarterial access not able to accommodate an 18Fr sheath.
Trial locations and contacts
45 sites in 1 country.
45 sites in 1 country
United States45 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
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
Pinnacle Health
Harrisburg, Pennsylvania, 17043
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
University of Kansas Hospital
Kansas City, Kansas, 66160
University of Southern California University Hospital
Los Angeles, California, 90033
Kaiser Permanente - Los Angeles Medical Center
Los Angeles, California, 90072
North Shore University Hospital/ Long Island Jewish 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, 33140
St. Luke's Medical Center - Aurora Health Care
Milwaukee, Wisconsin, 53215
Morristown Memorial Hospital
Morristown, New Jersey, 07962
El Camino Hospital
Mountain View, California, 94040
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
Providence Sacred Heart Medical Center
Spokane, Washington, 99204
Washington Hospital Center / Georgetown Hospital
Washington D.C., District of Columbia, 20010
Wake Forest University - Baptist Medical Center
Winston-Salem, North Carolina, 27157
About this study
Official title: Medtronic CoreValve® Continued Access Study
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.
- Conditions
- Severe Aortic Stenosis
- Being tested
- Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
- Keywords
- Valvular Heart Disease, Critical Aortic Stenosis, Severe Aortic Stenosis, Extreme Risk, High Risk, Aortic Valve Replacement
- Medical subject headings
- Aortic Valve Stenosis, Heart Valve Diseases
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 |
|---|---|---|
| Extreme Risk: TAVI Iliofemoral | Experimental | Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access Receives: Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) |
| Extreme Risk: TAVI Non-Iliofemoral | Experimental | Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access Receives: Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) |
| High Risk: TAVI | Experimental | High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) 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.
Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality
All-cause Death or Major Stroke (Extreme Risk- Medtronic CoreValve® System); All-cause Mortality (High Risk Surgical- Medtronic CoreValve® System vs. Surgical Valve)
Measured: 1 year
Secondary outcomes (19)
Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
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 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
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 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
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 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Conduction Disturbance Requiring Permanent Pacemaker Implantation
Measured: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Change From Baseline in NYHA Class
Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.
NYHA Classification:
Class I: Subjects with cardiac disease but without resulting limitations of physical activity.
Class I: Subjects with cardiac disease resulting in slight limitation of physical activity.
Class III: Subjects with cardiac disease resulting in marked limitation of physical activity.
Class IV: Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort.
Measured: 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.
Change From Baseline in Distance Walked During 6-Minute Walk Test (6MWT)
Change in distance walked during 6MWT from baseline
Measured: Baseline to 30 days, baseline to 1 year
Ratio of Days Alive Out of Hospital at 365 Days Post Procedure Versus Total Days Alive
Measured: 1 year
Quality of Life (QoL) Change
QoL summary score change from baseline using the following measures:
- Kansas City Cardiomyopathy Questionnaire (KCCQ): Quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
- 12 Item Short Form Health Survey (SF-12): Measures functional health and well-being. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
- European QoL (EQ-5D): Measures 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that can be converted to utilities using an algorithm. Utilities range from 0 to 1, with 1 representing perfect health, and 0 corresponding to the worst imaginable health state.
Measured: 30 day, 6 month, 1 year. The 2-5 year outcome data will be reported once data set is complete.
Echocardiographic Assessment of Valve Performance
Using the following measure:
- Effective Orifice Area (EOA) analyzed overall per Extreme Risk or High Risk. Iliofemoral access and non-iliofemoral access are not reported separate because this is a valve performance measurement.
Measured: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Echocardiographic Assessment of Valve Performance
Using the following measure:
- Transvalvular Mean Gradient analyzed overall per Extreme Risk or High Risk. Iliofemoral access and non-iliofemoral access are not reported separate because this is a valve performance measurement.
Measured: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Echocardiographic Assessment of Valve Performance
Using the following measure:
- Degree of Aortic Valve Regurgitation (Transvalvular and Paravalvular) analyzed overall per Extreme Risk or High Risk. Iliofemoral access and non-iliofemoral access are not reported separate because this is a valve performance measurement.
Measured: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Aortic Valve Hospitalizations
Measured: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Cardiovascular Deaths and Valve-Related Deaths
Measured: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Strokes and Transient Ischemic Attacks (TIAs)
Strokes (of any severity) and TIAs
Measured: 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Index Procedure Related MAEs
Measured: Procedure
Length of Index Procedure Hospital Stay
Measured: Number of days from admission to discharge
Device Success
Defined as:
- Successful vascular access, delivery and deployment of the device, and successful retrieval of the delivery system,
- Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function),
- 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)
- Only one valve implanted in the proper anatomical location
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
Prosthetic Valve Dysfunction (PVD)
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 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2012 (estimated)
- Study start21 Feb 2012
- Primary completionNov 2015
- Study completion18 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2,777 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medtronic Cardiovascular
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David H Adams, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01531374
- Sponsor's protocol ID
- 10037989DOC REV 1C
- Status last verified
- Oct 2022
- First submitted
- 3 Feb 2012
- Last updated
- 25 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 40175015Klautz 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.
PubMed 38710669O'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.
PubMed 36515976Butala 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 34529944Pineda 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.
PubMed 30341970Kleiman 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.
PubMed 27601429