Severe Aortic StenosisNCT01240902

Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement

A study testing Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) and Surgical Aortic Valve Replacement (SAVR) in people with Severe Aortic Stenosis, run by Medtronic Cardiovascular at 45 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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 high risk for aortic valve surgery and/or very 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) and Surgical Aortic Valve Replacement (SAVR)
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,453 participants
Where: 45 sitesUnited States
Study dates: 10 Dec 2010to 15 May 2019
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Extreme Risk Only: Subject must have comorbidities 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.
High Risk Surgical Only: Subject must have comorbidities 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.
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
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 intended treatment. (High Risk Surgical Only: Including bare metal stents. Additionally, any drug eluting stents placed within 6 months prior to the index 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.

Show all 41Show fewer

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 Gastrointestinal (GI) bleeding within the past 3 months.
A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated:
Aspirin
Heparin (HIT/HITTS)
Bivalirudin (Extreme Risk Only)
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.
Subject has been offered surgical aortic valve replacement but declined. (High Risk Surgical Only)
Anatomical
Native aortic annulus size < 18 mm or > 29 mm per the baseline diagnostic imaging.
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.
New or untreated echocardiographic evidence of 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 aorta 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.
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.

City, postcode or hospital

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/ Terrebone 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
Kaiser Permanente - Los Angeles Medical Center
Los Angeles, California, 90027
University of Southern California University Hospital
Los Angeles, California, 90033
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

Other trials in United States

About this study

Official title: Medtronic CoreValve® U.S. Pivotal Trial

Conditions: Severe Aortic Stenosis
Being tested: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI), Surgical Aortic Valve Replacement (SAVR)
Keywords: Valvular Heart Disease, Critical Aortic Stenosis, Severe Aortic Stenosis, 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
Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Surgical Aortic Valve Replacement (SAVR)Device
Surgical Aortic Valve Replacement (SAVR)

Study groups in NCT01240902
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)
High Risk: SAVR	Active comparator	High Risk Surgical Patients: Surgical Aortic Valve Replacement (SAVR) Receives: Device: Surgical Aortic Valve Replacement (SAVR)

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 Mortality
- 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 month, 1 year, 2 year
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 month, 1 year, 2 year
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 month, 1 year, 2 year
Conduction Disturbance Requiring Permanent Pacemaker Implantation
Measured: 30 day, 6 month, 1 year, 2 year
Change in NYHA Class
Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.
New York Heart Association (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: 30 day, 6 month, 1 year, 2 year
Change in Distance Walked During 6-Minute Walk Test (6MWT)
Change in distance walked during 6MWT from baseline
Measured: 30 day, 1 year
Ratio of Days Alive Out of Hospital 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, 2 year
Echocardiographic Assessment of Valve Performance
Using the following measures:
- Effective Orifice Area (EOA)
Measured: 30 day, 6 month, 1 year, 2 year
Echocardiographic Assessment of Valve Performance
Using the following measures:
- Transvalvular Mean Gradient
Measured: 30 day, 6 month, 1 year, 2 year
Echocardiographic Assessment of Valve Performance
Using the following measure:
- Degree of Aortic Valve Regurgitation (Transvalvular and Paravalvular)
Measured: 30 day, 6 month, 1 year, 2 year
Aortic Valve Hospitalizations
Measured: 30 day, 6 month, 1 year, 2 year
Cardiovascular Deaths and Valve Related Deaths
Measured: 30 day, 6 month, 1 year, 2 year
Strokes and Transient Ischemic Attacks (TIAs)
Strokes (of any severity) and TIAs
Measured: 30 day, 6 month, 1 year, 2 year
Index Procedure Related MAEs
Measured: Procedure
Length of Index Procedure Hospital Stay
Measured: Number of days from admission to discharge
Device Success
Medtronic CoreValve® System subjects only.
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
Medtronic CoreValve® System subjects only.
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 I using the Core Lab 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 month, 1 year, 2 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Dec 201015 May 2019

First posted15 Nov 2010 (estimated)
Study start10 Dec 2010
Primary completionAug 2014
Study completion15 May 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 (27)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: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 1,453 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01240902
Sponsor's protocol ID: MCV-US-2009-01
Status last verified: Oct 2022
First submitted: 10 Nov 2010
Last updated: 25 Oct 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

O'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 36515976
Lanz J, Reardon MJ, Pilgrim T, Stortecky S, Deeb GM, Chetcuti S, Yakubov SJ, Gleason TG, Huang J, Windecker S. Incidence and Outcomes of Infective Endocarditis After Transcatheter or Surgical Aortic Valve Replacement. J Am Heart Assoc. 2021 Oct 5;10(19):e020368. doi: 10.1161/JAHA.120.020368. Epub 2021 Sep 28.
PubMed 34581194
Arnold SV, Petrossian G, Reardon MJ, Kleiman NS, Yakubov SJ, Wang K, Hermiller J Jr, Harrison JK, Deeb GM, Huang J, Cohen DJ; US CoreValve Investigators. Five-Year Clinical and Quality of Life Outcomes From the CoreValve US Pivotal Extreme Risk Trial. Circ Cardiovasc Interv. 2021 Jun;14(6):e010258. doi: 10.1161/CIRCINTERVENTIONS.120.010258. Epub 2021 Jun 7.
PubMed 34092091
Arnold SV, Chinnakondepalli KM, Magnuson EA, Reardon MJ, Deeb GM, Gleason T, Yakubov SJ, Cohen DJ; CoreValve US Pivotal Trial Investigators. Five-Year Health Status After Self-expanding Transcatheter or Surgical Aortic Valve Replacement in High-risk Patients With Severe Aortic Stenosis. JAMA Cardiol. 2021 Jan 1;6(1):97-101. doi: 10.1001/jamacardio.2020.4397.
PubMed 32997095
Ito S, Nkomo VT, Orsinelli DA, Lin G, Cavalcante J, Popma JJ, Adams DH, Checuti SJ, Deeb GM, Boulware M, Huang J, Little SH, Cohen SA, Reardon MJ, Oh JK. Impact of Stroke Volume Index and Left Ventricular Ejection Fraction on Mortality After Aortic Valve Replacement. Mayo Clin Proc. 2020 Jan;95(1):69-76. doi: 10.1016/j.mayocp.2019.10.031.
PubMed 31902431
Lindman BR, Goel K, Bermejo J, Beckman J, O'Leary J, Barker CM, Kaiser C, Cavalcante JL, Elmariah S, Huang J, Hickey GL, Adams DH, Popma JJ, Reardon MJ. Lower Blood Pressure After Transcatheter or Surgical Aortic Valve Replacement is Associated with Increased Mortality. J Am Heart Assoc. 2019 Nov 5;8(21):e014020. doi: 10.1161/JAHA.119.014020. Epub 2019 Oct 31.
PubMed 31665959
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.
PubMed 30341970
Gleason TG, Reardon MJ, Popma JJ, Deeb GM, Yakubov SJ, Lee JS, Kleiman NS, Chetcuti S, Hermiller JB Jr, Heiser J, Merhi W, Zorn GL 3rd, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Conte JV, Mumtaz M, Oh JK, Huang J, Adams DH; CoreValve U.S. Pivotal High Risk Trial Clinical Investigators. 5-Year Outcomes of Self-Expanding Transcatheter Versus Surgical Aortic Valve Replacement in High-Risk Patients. J Am Coll Cardiol. 2018 Dec 4;72(22):2687-2696. doi: 10.1016/j.jacc.2018.08.2146. Epub 2018 Sep 21.
PubMed 30249462
Grayburn PA, Oh JK, Reardon MJ, Popma JJ, Deeb GM, Boulware M, Huang J, Stoler RC. Effect of Baseline Aortic Regurgitation on Mortality in Patients Treated With Transcatheter or Surgical Aortic Valve Replacement (from the CoreValve US Pivotal Trial). Am J Cardiol. 2018 Nov 1;122(9):1527-1535. doi: 10.1016/j.amjcard.2018.07.018. Epub 2018 Aug 3.
PubMed 30172363
Crestanello JA, Popma JJ, Adams DH, Deeb GM, Mumtaz M, George B, Huang J, Reardon MJ. Long-Term Health Benefit of Transcatheter Aortic Valve Replacement in Patients With Chronic Lung Disease. JACC Cardiovasc Interv. 2017 Nov 27;10(22):2283-2293. doi: 10.1016/j.jcin.2017.07.025. Epub 2017 Nov 1.
PubMed 29102579
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.
PubMed 27601429
Reardon MJ, Kleiman NS, Adams DH, Yakubov SJ, Coselli JS, Deeb GM, O'Hair D, Gleason TG, Lee JS, Hermiller JB Jr, Chetcuti S, Heiser J, Merhi W, Zorn GL 3rd, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Maini B, Mumtaz M, Conte JV, Resar JR, Aharonian V, Pfeffer T, Oh JK, Huang J, Popma JJ. Outcomes in the Randomized CoreValve US Pivotal High Risk Trial in Patients With a Society of Thoracic Surgeons Risk Score of 7% or Less. JAMA Cardiol. 2016 Nov 1;1(8):945-949. doi: 10.1001/jamacardio.2016.2257.
PubMed 27541162
Popma JJ, Reardon MJ, Yakubov SJ, Hermiller JB Jr, Harrison JK, Gleason TG, Conte JV, Deeb GM, Chetcuti S, Oh JK, Boulware MJ, Huang J, Adams DH; CoreValve US Clinical Investigators. Safety and Efficacy of Self-Expanding TAVR in Patients With Aortoventricular Angulation. JACC Cardiovasc Imaging. 2016 Aug;9(8):973-81. doi: 10.1016/j.jcmg.2016.06.002.
PubMed 27491485
Hermiller JB Jr, Yakubov SJ, Reardon MJ, Deeb GM, Adams DH, Afilalo J, Huang J, Popma JJ; CoreValve United States Clinical Investigators. Predicting Early and Late Mortality After Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2016 Jul 26;68(4):343-52. doi: 10.1016/j.jacc.2016.04.057.
PubMed 27443429
Popma JJ, Gleason TG, Yakubov SJ, Harrison JK, Forrest JK, Maini B, Ruiz CE, Pinto DS, Costa M, Resar J, Conte J, Crestanello J, Chang Y, Oh JK, Reardon MJ, Adams DH. Relationship of Annular Sizing Using Multidetector Computed Tomographic Imaging and Clinical Outcomes After Self-Expanding CoreValve Transcatheter Aortic Valve Replacement. Circ Cardiovasc Interv. 2016 Jul;9(7):e003282. doi: 10.1161/CIRCINTERVENTIONS.115.003282.
PubMed 27369803

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Medtronic CoreValve® U.S. Pivotal Trial
ClinicalTrials.gov ID: NCT01240902
Acronym / sponsor ID: MCV-US-2009-01
Conditions: Severe Aortic Stenosis
Keywords: Valvular Heart Disease, Critical Aortic Stenosis, Severe Aortic Stenosis, High Risk, Aortic Valve Replacement
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,453 participants (actual)
Lead sponsor: Medtronic CardiovascularIndustry (pharma, biotech, devices)
Study start: 10 Dec 2010 (actual)
Primary completion: Aug 2014 (actual)
Study completion: 15 May 2019 (actual)
First posted: 15 Nov 2010 (estimated)
Results: Posted 8 Jun 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Extreme Risk: TAVI Iliofemoral	Experimental	Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access
Extreme Risk: TAVI Non-Iliofemoral	Experimental	Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access
High Risk: TAVI	Experimental	Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
High Risk: SAVR	Active comparator	Device: Surgical Aortic Valve Replacement (SAVR)High Risk Surgical Patients: Surgical Aortic Valve Replacement (SAVR)

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (6 listed)

Extreme Risk Only: Subject must have comorbidities 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.
High Risk Surgical Only: Subject must have comorbidities 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.
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
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.

Key exclusion criteria (41 listed)

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 intended treatment. (High Risk Surgical Only: Including bare metal stents. Additionally, any drug eluting stents placed within 6 months prior to the index 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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)	Device	Extreme Risk: TAVI Iliofemoral, Extreme Risk: TAVI Non-Iliofemoral, High Risk: TAVI
Surgical Aortic Valve Replacement (SAVR)Surgical Aortic Valve Replacement (SAVR)	Device	High Risk: SAVR

Primary outcome

Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality
Time frame: 1 year
All-cause Death or Major Stroke (Extreme Risk- Medtronic CoreValve® System); All-cause Mortality (High Risk Surgical- Medtronic CoreValve® System vs. Surgical Valve)

19 secondary outcomes

Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
Time frame: 30 day, 6 month, 1 year, 2 year
The Occurrence of Individual MACCE Components
Time frame: 30 day, 6 month, 1 year, 2 year
Major Adverse Events (MAEs)
Time frame: 30 day, 6 month, 1 year, 2 year
Conduction Disturbance Requiring Permanent Pacemaker Implantation
Time frame: 30 day, 6 month, 1 year, 2 year
Change in NYHA Class
Time frame: 30 day, 6 month, 1 year, 2 year
Change in Distance Walked During 6-Minute Walk Test (6MWT)
Time frame: 30 day, 1 year
Ratio of Days Alive Out of Hospital Versus Total Days Alive
Time frame: 1 year
Quality of Life (QoL) Change
Time frame: 30 day, 6 month, 1 year, 2 year
Echocardiographic Assessment of Valve Performance
Time frame: 30 day, 6 month, 1 year, 2 year
Echocardiographic Assessment of Valve Performance
Time frame: 30 day, 6 month, 1 year, 2 year
Echocardiographic Assessment of Valve Performance
Time frame: 30 day, 6 month, 1 year, 2 year
Aortic Valve Hospitalizations
Time frame: 30 day, 6 month, 1 year, 2 year
Cardiovascular Deaths and Valve Related Deaths
Time frame: 30 day, 6 month, 1 year, 2 year
Strokes and Transient Ischemic Attacks (TIAs)
Time frame: 30 day, 6 month, 1 year, 2 year
Index Procedure Related MAEs
Time frame: Procedure
Length of Index Procedure Hospital Stay
Time frame: Number of days from admission to discharge
Device Success
Time frame: Number of days from admission to discharge
Procedural Success
Time frame: Number of days from admission to discharge
Prosthetic Valve Dysfunction (PVD)
Time frame: 30 day, 6 month, 1 year, 2 year

Results and safety

Results posted to the registry on 8 Jun 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Extreme Risk: TAVI Iliofemoral	500	289
Extreme Risk: TAVI Non-Iliofemoral	156	77
High Risk: TAVI	395	295
High Risk: SAVR	402	237

Primary outcome: Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality

Time frame: 1 year. Number. Unit: percentage of participants, Kaplan-Meier

Measure	Extreme Risk: TAVI Iliofemoral n = 489	Extreme Risk: TAVI Non-Iliofemoral n = 150	High Risk: TAVI n = 391	High Risk: SAVR n = 359
Value	26.0	39.3	14.1	18.9

Extreme Risk: TAVI Iliofemoral: Kaplan-Meier: 26.0 (95% CI 22.3 to 30.1), p <0.0001, z-test, 1 sided
Extreme Risk: TAVI Non-Iliofemoral: Kaplan-Meier: 39.3
High Risk: TAVI: p <0.0001, z-test, 1 sided

Population analysed: Participant Population= Consisted of all subjects with an attempted implant procedure.

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AEs) were collected from study enrollment to study closure, up to 5 years. Adverse event data are currently available and reported for up to 1 year. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Extreme Risk: TAVI Iliofemoral	452 of 489 (92.4%)	440 of 489 (90%)	Not reported
Extreme Risk: TAVI Non-Iliofemoral	142 of 150 (94.7%)	139 of 150 (92.7%)	Not reported
High Risk: TAVI	346 of 390 (88.7%)	355 of 390 (91%)	Not reported
High Risk: SAVR	324 of 357 (90.8%)	320 of 357 (89.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36515976O'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.
Derived from this study: PubMed 34581194Lanz J, Reardon MJ, Pilgrim T, Stortecky S, Deeb GM, Chetcuti S, Yakubov SJ, Gleason TG, Huang J, Windecker S. Incidence and Outcomes of Infective Endocarditis After Transcatheter or Surgical Aortic Valve Replacement. J Am Heart Assoc. 2021 Oct 5;10(19):e020368. doi: 10.1161/JAHA.120.020368. Epub 2021 Sep 28.
Derived from this study: PubMed 34092091Arnold SV, Petrossian G, Reardon MJ, Kleiman NS, Yakubov SJ, Wang K, Hermiller J Jr, Harrison JK, Deeb GM, Huang J, Cohen DJ; US CoreValve Investigators. Five-Year Clinical and Quality of Life Outcomes From the CoreValve US Pivotal Extreme Risk Trial. Circ Cardiovasc Interv. 2021 Jun;14(6):e010258. doi: 10.1161/CIRCINTERVENTIONS.120.010258. Epub 2021 Jun 7.
Derived from this study: PubMed 32997095Arnold SV, Chinnakondepalli KM, Magnuson EA, Reardon MJ, Deeb GM, Gleason T, Yakubov SJ, Cohen DJ; CoreValve US Pivotal Trial Investigators. Five-Year Health Status After Self-expanding Transcatheter or Surgical Aortic Valve Replacement in High-risk Patients With Severe Aortic Stenosis. JAMA Cardiol. 2021 Jan 1;6(1):97-101. doi: 10.1001/jamacardio.2020.4397.
Derived from this study: PubMed 31902431Ito S, Nkomo VT, Orsinelli DA, Lin G, Cavalcante J, Popma JJ, Adams DH, Checuti SJ, Deeb GM, Boulware M, Huang J, Little SH, Cohen SA, Reardon MJ, Oh JK. Impact of Stroke Volume Index and Left Ventricular Ejection Fraction on Mortality After Aortic Valve Replacement. Mayo Clin Proc. 2020 Jan;95(1):69-76. doi: 10.1016/j.mayocp.2019.10.031.
Derived from this study: PubMed 31665959Lindman BR, Goel K, Bermejo J, Beckman J, O'Leary J, Barker CM, Kaiser C, Cavalcante JL, Elmariah S, Huang J, Hickey GL, Adams DH, Popma JJ, Reardon MJ. Lower Blood Pressure After Transcatheter or Surgical Aortic Valve Replacement is Associated with Increased Mortality. J Am Heart Assoc. 2019 Nov 5;8(21):e014020. doi: 10.1161/JAHA.119.014020. Epub 2019 Oct 31.
Derived from this study: PubMed 30341970Pineda 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.
Derived from this study: PubMed 30249462Gleason TG, Reardon MJ, Popma JJ, Deeb GM, Yakubov SJ, Lee JS, Kleiman NS, Chetcuti S, Hermiller JB Jr, Heiser J, Merhi W, Zorn GL 3rd, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Conte JV, Mumtaz M, Oh JK, Huang J, Adams DH; CoreValve U.S. Pivotal High Risk Trial Clinical Investigators. 5-Year Outcomes of Self-Expanding Transcatheter Versus Surgical Aortic Valve Replacement in High-Risk Patients. J Am Coll Cardiol. 2018 Dec 4;72(22):2687-2696. doi: 10.1016/j.jacc.2018.08.2146. Epub 2018 Sep 21.
Derived from this study: PubMed 30172363Grayburn PA, Oh JK, Reardon MJ, Popma JJ, Deeb GM, Boulware M, Huang J, Stoler RC. Effect of Baseline Aortic Regurgitation on Mortality in Patients Treated With Transcatheter or Surgical Aortic Valve Replacement (from the CoreValve US Pivotal Trial). Am J Cardiol. 2018 Nov 1;122(9):1527-1535. doi: 10.1016/j.amjcard.2018.07.018. Epub 2018 Aug 3.
Derived from this study: PubMed 29102579Crestanello JA, Popma JJ, Adams DH, Deeb GM, Mumtaz M, George B, Huang J, Reardon MJ. Long-Term Health Benefit of Transcatheter Aortic Valve Replacement in Patients With Chronic Lung Disease. JACC Cardiovasc Interv. 2017 Nov 27;10(22):2283-2293. doi: 10.1016/j.jcin.2017.07.025. Epub 2017 Nov 1.
Derived from this study: PubMed 27601429Kleiman 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.
Derived from this study: PubMed 27541162Reardon MJ, Kleiman NS, Adams DH, Yakubov SJ, Coselli JS, Deeb GM, O'Hair D, Gleason TG, Lee JS, Hermiller JB Jr, Chetcuti S, Heiser J, Merhi W, Zorn GL 3rd, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Maini B, Mumtaz M, Conte JV, Resar JR, Aharonian V, Pfeffer T, Oh JK, Huang J, Popma JJ. Outcomes in the Randomized CoreValve US Pivotal High Risk Trial in Patients With a Society of Thoracic Surgeons Risk Score of 7% or Less. JAMA Cardiol. 2016 Nov 1;1(8):945-949. doi: 10.1001/jamacardio.2016.2257.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David H Adams, MD principal investigator

Icahn School of Medicine at Mount Sinai

45 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01240902, which also lists 27 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2022.