CompletedNCT01240902Updated Oct 25, 2022Results posted

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

An interventional study of Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) and Surgical Aortic Valve Replacement (SAVR) in Severe Aortic Stenosis, sponsored by Medtronic Cardiovascular. Completed at 45 sites in United States. Per ClinicalTrials.gov, last updated 2022-10-25.

Sponsored by Medtronic Cardiovascular (part of Medtronic) · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 1,453
Allocation: Randomized
Sex: All

Study 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.

Conditions studied

Severe Aortic Stenosis

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Keywords

Valvular Heart Disease
Critical Aortic Stenosis
Severe Aortic Stenosis
High Risk
Aortic Valve Replacement

In context

Aortic Valve Stenosis

1,006 studies on the registry are indexed under Aortic Valve Stenosis; 284 are open to participants now.

This study's enrollment of 1,453 is above the median of 120 across 537 interventional studies indexed under Aortic Valve Stenosis.

Browse Aortic Valve Stenosis studies →

Lead sponsor

Medtronic Cardiovascular is the lead sponsor of 70 studies on the registry; 7 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 5 (100%) have results posted.

Browse Medtronic Cardiovascular studies →All Medtronic studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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.

Exclusion criteria

Exclusion Criteria:

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.
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.

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 1,453 participants (actual)

Study arms

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

Interventions

DeviceMedtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
DeviceSurgical Aortic Valve Replacement (SAVR)
Surgical Aortic Valve Replacement (SAVR)

What researchers measure

Primary outcomes

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)
Time frame: 1 year

Secondary outcomes

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)
Time frame: 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)
Time frame: 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
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
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.
Time frame: 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
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
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.
Time frame: 30 day, 6 month, 1 year, 2 year
Echocardiographic Assessment of Valve Performance
Using the following measures: \- Effective Orifice Area (EOA)
Time frame: 30 day, 6 month, 1 year, 2 year
Echocardiographic Assessment of Valve Performance
Using the following measures: \- Transvalvular Mean Gradient
Time frame: 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)
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)
Strokes (of any severity) and 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
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
Time frame: Number of days from admission to discharge
Procedural Success
Medtronic CoreValve® System subjects only. Defined as device success and absence of in-hospital MACCE.
Time frame: 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
Time frame: 30 day, 6 month, 1 year, 2 year

Results

Posted Jun 8, 2015

Participant flow

Between Feb 17, 2011 and Aug 23, 2013, 656 subjects were enrolled into the CoreValve US Pivotal Trial Extreme Risk study at 41 of the 43 activated centers in the United States. Between February 2, 2011 and July 23, 2013, 797 subjects were enrolled into the CoreValve US Pivotal Trial High Risk study at 45 centers in the United States.

Participant flow — Overall Study
Milestone	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
Started	500	156	395	402
Completed	289	77	295	237
Not completed	211	79	100	165

Outcome measures

PrimaryExtreme 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)

Time frame:: 1 year
Reported as:: Number · percentage of participants, Kaplan-Meier

Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality
percentage of participants, Kaplan-Meier	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality	26.0	39.3	14.1	18.9

Statistical analysis

Extreme Risk: TAVI Iliofemoral · z-test, 1 sided · p = <0.0001 · Kaplan-meier: 26.0 · 95% CI 22.3 to 30.1Kaplan-Meier Event Rate Greenwood Standard Error
Extreme Risk: TAVI Non-Iliofemoral · Kaplan-meier: 39.3Kaplan-Meier Event Rate Greenwood Standard Error
High Risk: TAVI · z-test, 1 sided · p = <0.0001

SecondaryMajor 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)

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Number · percentage of participants, Kaplan-Meier

Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
percentage of participants, Kaplan-Meier	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day	12.3	17.3	7.7	10.3
6 month	22.5	34.7	15.4	21.0
1 year	29.2	41.4	20.5	27.0
2 Year	42.3	51.0	29.7	38.6

Statistical analysis

High Risk: TAVI vs High Risk: SAVR · Kaplan-Meier Point Estimate · p = 0.1033 (Hierarchical test item #5, MACCE at 30 days or hospital discharge; whichever was longer. K-M rates TAVR 8.21%, SAVR 10.93%, Difference -2.73%, Standard Error 2.16%, and Upper 95% CI 1.5%.)Using Greenwood formula

SecondaryThe 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)

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Number · percentage of participants, Kaplan-Meier

The Occurrence of Individual MACCE Components
percentage of participants, Kaplan-Meier	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day All Cause Mortality	8.4	11.3	3.3	4.5
30 day MI	1.2	2.1	0.8	0.8
30 day Stroke	4.0	8.8	4.9	6.2
30 day Reintervention	1.1	0.0	0.8	0.0
6 month All Cause Mortality	18.6	28.7	9.0	14.0
6 month MI	1.5	2.1	1.6	1.1
6 month Stroke	5.2	12.0	7.3	9.9
6 month Reintervention	1.5	0.0	1.0	0.0
1 year All Cause Mortality	24.3	36.0	14.1	18.9
1 year MI	2.0	2.1	1.9	1.5
1 year Stroke	7.0	13.0	8.7	12.5
1 year Reintervention	1.8	1.0	2.2	0.0
2 year All Cause Mortality	36.6	44.9	22.2	28.6
2 year MI	2.8	3.2	1.9	2.3
2 year Stroke	8.6	16.1	10.9	16.6
2 year Reintervention	1.8	1.0	2.5	0.4

SecondaryMajor 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

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Number · percentage of participants, Kaplan-Meier

Major Adverse Events (MAEs)
percentage of participants, Kaplan-Meier	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day	54.2	69.3	52.4	50.2
6 month	60.5	76.0	58.6	76.4
1 year	63.4	80.0	60.1	59.8
2 year	71.3	84.0	66.4	66.8

SecondaryConduction Disturbance Requiring Permanent Pacemaker Implantation

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Number · percentage of participants, Kaplan-Meier

Conduction Disturbance Requiring Permanent Pacemaker Implantation
percentage of participants, Kaplan-Meier	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day	21.6	16.4	20.0	7.1
6 month	24.4	20.5	21.9	9.9
1 year	26.4	21.5	22.5	11.6
2 year	28.8	22.6	25.8	12.8

SecondaryChange 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.

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Mean · average classification level change

Change in NYHA Class
average classification level change	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day	-1.3 ± 0.9	-1.0 ± 0.8	-1.3 ± 0.8	-1.0 ± 0.9
6 month	-1.6 ± 0.9	-1.4 ± 0.8	-1.5 ± 0.8	-1.4 ± 0.8
1 year	-1.6 ± 0.9	-1.4 ± 0.8	-1.5 ± 0.8	-1.5 ± 0.8
2 year	-1.6 ± 0.8	-1.4 ± 0.7	-1.5 ± 0.8	-1.5 ± 0.9

Statistical analysis

Extreme Risk: TAVI Iliofemoral · t-test, 2 sided · p = <0.0001 (Hierarchical test item #3, change from baseline to 1 year.) · Mean difference (net): -1.6
High Risk: TAVI vs High Risk: SAVR · t-test, 1 sided · p = <0.0001 (Hierarchical test item #3, change from baseline to 1 year.)

SecondaryChange in Distance Walked During 6-Minute Walk Test (6MWT)

Change in distance walked during 6MWT from baseline

Time frame:: 30 day, 1 year
Reported as:: Mean · meters

Change in Distance Walked During 6-Minute Walk Test (6MWT)
meters	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day	19.6 ± 109.1	13.3 ± 110.0	25.8 ± 105.5	-6.9 ± 89.8
1 year	13.9 ± 140.4	22.2 ± 136.2	27.0 ± 114.3	24.0 ± 111.8

SecondaryRatio of Days Alive Out of Hospital Versus Total Days Alive

Time frame:: 1 year
Reported as:: Mean · ratio of days alive and out of hospital

Ratio of Days Alive Out of Hospital Versus Total Days Alive
ratio of days alive and out of hospital	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
Ratio of Days Alive Out of Hospital Versus Total Days Alive	0.86 ± 0.28	0.81 ± 0.31	0.92 ± 0.20	0.89 ± 0.23

SecondaryQuality 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.

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Mean · units on a scale

Quality of Life (QoL) Change
units on a scale	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day KCCQ- Overall	24.2 ± 28.9	7.9 ± 33.5	19.0 ± 29.4	4.3 ± 28.1
30 day KCCQ- Clinical	20.2 ± 28.0	6.8 ± 32.0	14.7 ± 28.6	2.7 ± 27.1
30 day SF-12-Physical	5.9 ± 10.4	1.9 ± 10.4	4.9 ± 10.2	-0.0 ± 10.1
30 day SF-12-Mental	3.7 ± 14.2	-1.7 ± 16.2	2.6 ± 13.1	-2.5 ± 13.4
30 day EQ-5D	0.09 ± 0.29	0.00 ± 0.30	0.04 ± 0.24	-0.07 ± 0.26
6 month KCCQ-Overall	27.4 ± 27.0	23.1 ± 28.3	24.8 ± 26.9	22.9 ± 26.4
6 month KCCQ- Clinical	22.2 ± 26.1	17.5 ± 26.6	18.6 ± 25.7	17.7 ± 25.7
6 month SF-12-Physical	5.2 ± 11.3	4.5 ± 8.9	6.3 ± 11.0	6.2 ± 9.9
6 month SF-12-Mental	4.6 ± 13.6	4.4 ± 13.8	4.6 ± 11.8	2.6 ± 13.1
6 month EQ-5D	0.09 ± 0.22	0.05 ± 0.21	0.05 ± 0.22	0.04 ± 0.17
1 year KCCQ-Overall	27.9 ± 27.1	21.9 ± 26.8	23.2 ± 25.4	21.8 ± 26.5
1 year KCCQ- Clinical	20.8 ± 26.8	18.1 ± 24.9	16.7 ± 25.5	15.2 ± 26.0
1 year SF-12-Physical	5.5 ± 10.8	4.6 ± 10.0	6.0 ± 11.5	5.3 ± 10.3
1 year SF-12-Mental	5.2 ± 13.7	2.4 ± 14.3	4.5 ± 11.8	3.2 ± 12.1
1 year EQ-5D	0.06 ± 0.25	0.05 ± 0.25	0.04 ± 0.19	0.01 ± 0.19
2 year KCCQ - Overall	25.2 ± 27.2	14.9 ± 29.5	22.2 ± 26.5	18.7 ± 25.6
2 year KCCQ - Clinical	18.8 ± 26.1	11.6 ± 26.9	14.6 ± 26.0	12.6 ± 25.8
2 year SF-12 - Physical	4.0 ± 11.2	1.9 ± 11.9	5.0 ± 12.1	4.3 ± 10.2
2 year SF-12 - Mental	3.8 ± 15.3	2.2 ± 14.8	3.6 ± 13.0	1.7 ± 13.0
2 year EQ-5D	0.04 ± 0.25	0.03 ± 0.26	-0.01 ± 0.24	-0.01 ± 0.21

Statistical analysis

Extreme Risk: TAVI Iliofemoral · t-test, 2 sided · p = <0.0001 (Hierarchical test item #4)
High Risk: TAVI vs High Risk: SAVR · t-test, 1 sided · p = 0.0063 (Hierarchical test item #4)
High Risk: TAVI vs High Risk: SAVR · t-test, 2 sided · p = <0.0001 (Hierarchical test item #6. Item #5 failed, therefore, item #6 also fails. Nominal p- value provided.)

SecondaryEchocardiographic Assessment of Valve Performance

Using the following measures: \- Effective Orifice Area (EOA)

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Mean · cm^2

Echocardiographic Assessment of Valve Performance
cm^2	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day EOA	1.86 ± 0.56	1.82 ± 0.64	1.94 ± 0.56	1.60 ± 0.51
6 month EOA	1.88 ± 0.55	1.85 ± 0.51	1.91 ± 0.53	1.56 ± 0.49
1 year EOA	1.88 ± 0.54	1.85 ± 0.51	1.91 ± 0.52	1.57 ± 0.49
2 year EOA	1.86 ± 0.55	1.83 ± 0.58	1.87 ± 0.48	1.51 ± 0.43

Statistical analysis

Extreme Risk: TAVI Iliofemoral · t-test, 2 sided · p = <0.0001 (Hierarchical test item #2)
High Risk: TAVI vs High Risk: SAVR · t-test, 1 sided · p = <0.0001 (Hierarchical test item #2)

SecondaryEchocardiographic Assessment of Valve Performance

Using the following measures: \- Transvalvular Mean Gradient

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Mean · mmHg

Echocardiographic Assessment of Valve Performance
mmHg	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day Mean Gradient	8.68 ± 4.16	9.74 ± 5.82	8.88 ± 3.86	11.72 ± 5.70
6 month Mean Gradient	9.10 ± 3.89	9.42 ± 5.60	9.08 ± 4.08	12.12 ± 6.31
1 year Mean Gradient	8.86 ± 4.09	9.46 ± 5.65	9.09 ± 3.49	12.44 ± 7.36
2 year Mean Gradient	8.70 ± 4.22	9.24 ± 5.35	8.47 ± 3.76	12.05 ± 6.32

Statistical analysis

Extreme Risk: TAVI Iliofemoral · t-test, 2 sided · p = <0.0001 (Hierarchical test item #1)
High Risk: TAVI vs High Risk: SAVR · t-test, 1 sided · p = <0.0001 (Hierarchical test item #1)

SecondaryEchocardiographic Assessment of Valve Performance

Using the following measure: \- Degree of Aortic Valve Regurgitation (Transvalvular and Paravalvular)

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Number · percentage of participants

Echocardiographic Assessment of Valve Performance
percentage of participants	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day Total Aortic Regurgitation- None	9.1	19.0	12.2	65.0
30 day Total Aortic Regurgitation- Trivial	32.7	33.9	41.4	23.0
30 day Total Aortic Regurgitation- Mild	43.0	34.7	36.4	10.7
30 day Total Aortic Regurgitation- Moderate	14.1	10.7	8.1	1.3
30 day Total Aortic Regurgitation- Severe	1.2	1.7	1.9	0.0
6 month Total Aortic Regurgitation- None	19.9	33.3	21.6	60.6
6 month Total Aortic Regurgitation- Trivial	33.5	27.1	37.2	28.0
6 month Total Aortic Regurgitation- Mild	36.5	35.4	29.7	9.8
6 month Total Aortic Regurgitation- Moderate	9.8	4.2	10.0	1.6
6 month Total Aortic Regurgitation- Severe	0.3	0.0	1.6	0.0
1 year Total Aortic Regurgitation- None	21.5	39.0	28.3	68.1
1 year Total Aortic Regurgitation- Trivial	40.6	36.6	35.7	21.7
1 year Total Aortic Regurgitation- Mild	31.5	20.7	29.0	8.8
1 year Total Aortic Regurgitation- Moderate	6.4	2.4	6.7	0.9
1 year Total Aortic Regurgitation- Severe	0.0	1.2	0.3	0.4
2 year Total Aortic Regurgitation - None	31.0	35.3	32.8	58.5
2 year Total Aortic Regurgitation - Trivial	26.3	36.8	27.0	27.3
2 year Total Aortic Regurgitation - Mild	36.1	23.5	32.0	13.1
2 year Total Aortic Regurgitation - Moderate	6.7	4.4	6.6	1.1
2 year Total Aortic Regurgitation - Severe	0.0	0.0	1.6	0.0

SecondaryAortic Valve Hospitalizations

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Number · percentage of participants, Kaplan-Meier

Aortic Valve Hospitalizations
percentage of participants, Kaplan-Meier	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day	6.7	8.7	3.9	5.2
6 month	16.4	18.3	13.4	9.0
1 year	21.9	21.2	16.5	14.0
2 year	29.5	27.2	24.2	18.2

SecondaryCardiovascular Deaths and Valve Related Deaths

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Number · percentage of participants, Kaplan-Meier

Cardiovascular Deaths and Valve Related Deaths
percentage of participants, Kaplan-Meier	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day Cardiovascular Deaths	8.4	11.3	3.3	4.5
30 Day Valve Related Deaths	2.5	2.8	2.3	0.6
6 month Cardiovascular Deaths	15.0	23.6	7.4	10.5
6 month Valve Related Deaths	4.1	4.5	3.6	1.8
1 year Cardiovascular Deaths	18.3	28.7	10.6	12.9
1 year Valve Related Deaths	5.1	5.4	5.6	2.2
2 year Cardiovascular Deaths	26.2	35.1	15.4	19.4
2 year Valve Related Deaths	6.2	7.5	6.8	4.2

SecondaryStrokes and Transient Ischemic Attacks (TIAs)

Strokes (of any severity) and TIAs

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Number · percentage of participants, Kaplan-Meier

Strokes and Transient Ischemic Attacks (TIAs)
percentage of participants, Kaplan-Meier	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day	4.6	10.2	5.7	6.5
6 month	6.0	14.3	8.4	10.8
1 year	8.1	15.2	10.3	14.1
2 year	10.1	19.5	13.2	17.8

SecondaryIndex Procedure Related MAEs

Time frame:: Procedure
Reported as:: Number · percentage of participants

Index Procedure Related MAEs
percentage of participants	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
Index Procedure Related MAEs	53.5	68.9	52.6	49.9

SecondaryLength of Index Procedure Hospital Stay

Time frame:: Number of days from admission to discharge
Reported as:: Mean · days

Length of Index Procedure Hospital Stay
days	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
Length of Index Procedure Hospital Stay	9.2 ± 8.1	11.2 ± 8.9	8.0 ± 6.8	12.5 ± 10.7

SecondaryDevice 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

Time frame:: Number of days from admission to discharge
Reported as:: Number · percentage of participants

Device Success
percentage of participants	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
Device Success	84.6	88.7	86.8	—

SecondaryProcedural Success

Medtronic CoreValve® System subjects only. Defined as device success and absence of in-hospital MACCE.

Time frame:: Number of days from admission to discharge
Reported as:: Number · percentage of participants

Procedural Success
percentage of participants	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
Procedural Success	77.5	77.5	81.3	—

SecondaryProsthetic 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

Time frame:: 30 day, 6 month, 1 year, 2 year
Reported as:: Number · percentage of participants

Prosthetic Valve Dysfunction (PVD)
percentage of participants	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
30 day Aortic Stenosis	2.3	6.1	3.1	4.8
30 day Aortic Regurgitation	23.5	16.9	13.6	1.7
6 month Aortic Stenosis	3.1	6.1	3.8	6.5
6 month Aortic Regurgitation	26.1	18.2	17.2	2.3
1 year Aortic Stenosis	3.5	6.1	4.9	8.2
1 year Aortic Regurgitation	27.0	19.6	17.9	2.8
2 year Aortic Stenosis	3.9	6.8	5.4	9.3
2 year Aortic Regurgitation	27.8	19.6	19.7	2.8

Adverse events

Collected over 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. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Extreme Risk: TAVI Iliofemoral	—	452/489 (92.4%)	440/489 (90%)
Extreme Risk: TAVI Non-Iliofemoral	—	142/150 (94.7%)	139/150 (92.7%)
High Risk: TAVI	—	346/390 (88.7%)	355/390 (91%)
High Risk: SAVR	—	324/357 (90.8%)	320/357 (89.6%)

Most frequent serious events

Showing 10 of 362

Most frequent serious events
Event	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
Anaemias NecBlood and lymphatic system disorders	140/489	70/150	106/390	151/357
Heart Failures NecCardiac disorders	117/489	29/150	69/390	62/357
Cardiac Conduction DisordersCardiac disorders	106/489	24/150	79/390	18/357
Renal Failure And ImpairmentRenal and urinary disorders	90/489	31/150	38/390	58/357
Supraventricular ArrhythmiasCardiac disorders	65/489	17/150	43/390	69/357
Pneumothorax And Pleural Effusions NecRespiratory, thoracic and mediastinal disorders	54/489	26/150	29/390	67/357
Respiratory Failures (Excl Neonatal)Respiratory, thoracic and mediastinal disorders	54/489	28/150	36/390	54/357
Ventricular Arrhythmias And Cardiac ArrestCardiac disorders	48/489	26/150	27/390	27/357
Lower Respiratory Tract And Lung InfectionsInfections and infestations	74/489	25/150	44/390	36/357
Breathing AbnormalitiesRespiratory, thoracic and mediastinal disorders	26/489	21/150	30/390	26/357

Most frequent other events

Showing 10 of 37

Most frequent other events
Event	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
Pneumothorax And Pleural Effusions NecReproductive system and breast disorders	76/489	30/150	52/390	91/357
ThrombocytopeniasBlood and lymphatic system disorders	68/489	32/150	61/390	90/357
Supraventricular ArrhythmiasCardiac disorders	60/489	36/150	59/390	80/357
Cardiac Conduction DisordersCardiac disorders	114/489	32/150	80/390	54/357
Anaemias NecBlood and lymphatic system disorders	90/489	27/150	76/390	69/357
Urinary Tract InfectionsInfections and infestations	75/489	28/150	51/390	58/357
Vascular Hypotensive DisordersVascular disorders	68/489	18/150	40/390	40/357
Renal Failure And ImpairmentRenal and urinary disorders	67/489	16/150	40/390	44/357
Vascular Hypertensive Disorders NecVascular disorders	45/489	20/150	46/390	37/357
Leukocytoses NecBlood and lymphatic system disorders	38/489	18/150	25/390	46/357

Baseline characteristics

Participant Population= As Treated (AT) cohort. The AT cohort consisted of all Intent to Treat (ITT) subjects with an attempted implant procedure.

Age, Continuous
Age, Continuous(years)	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR	Total
Mean	83.2 ± 8.7	81.3 ± 7.4	83.2 ± 7.1	83.3 ± 6.4	83.0 ± 7.6

Sex: Female, Male
Sex: Female, Male(Participants)	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR	Total
Female	255	82	184	171	692
Male	234	68	207	188	697

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR	Total
American Indian or Alaska Native	0	0	0	1	1
Asian	2	1	0	1	4
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	19	5	3	11	38
White	468	143	387	343	1341
More than one race	0	0	0	0	0
Unknown or Not Reported	0	1	1	2	4

Body Surface Area
Body Surface Area(m^2)	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR	Total
Mean	1.8 ± 0.3	1.8 ± 0.2	1.8 ± 0.2	1.9 ± 0.2	1.8 ± 0.2

NYHA Classification
NYHA Classification(participants)	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR	Total
NYHA I	0	0	0	0	0
NYHA II	40	12	57	47	156
NYHA III	313	98	255	250	916
NYHA IV	136	40	79	62	317

Society of Thoracic Surgeons (STS) Risk Score
Society of Thoracic Surgeons (STS) Risk Score(% risk of mortality or morbidity)	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR	Total
Mean	10.3 ± 5.5	10.7 ± 5.7	7.3 ± 3.0	7.5 ± 3.3	8.8 ± 4.7

Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE)
Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE)(%)	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR	Total
Mean	22.6 ± 17.1	22.9 ± 15.9	17.7 ± 13.0	18.8 ± 13.2	20.3 ± 15.1

Study locations

45 sites

Banner Good Samaritan
Phoenix, Arizona 85006, United States
Kaiser Permanente - Los Angeles Medical Center
Los Angeles, California 90027, United States
University of Southern California University Hospital
Los Angeles, California 90033, United States
El Camino Hospital
Mountain View, California 94040, United States
VA Palo Alto Health Care System
Palo Alto, California 94304, United States
Hartford Hospital
Hartford, Connecticut 06102, United States
Yale New Haven Hospital
New Haven, Connecticut 06520, United States
Washington Hospital Center / Georgetown Hospital
Washington D.C., District of Columbia 20010, United States
University of Miami Health System / Jackson Memorial Hospital
Miami, Florida 33136, United States
Mount Sinai Medical Center
Miami Beach, Florida 33140, United States
Piedmont Heart Institute
Atlanta, Georgia 30309, United States
Saint Joseph's Hospital of Atlanta
Atlanta, Georgia 30342, United States
Loyola University Medical Center
Maywood, Illinois 60153, United States
St. Vincent Heart Center of Indiana
Indianapolis, Indiana 46290, United States
Iowa Heart Center
Des Moines, Iowa 50314, United States
University of Kansas Hospital
Kansas City, Kansas 66160, United States
Cardiovascular Institute of the South/ Terrebone General
Houma, Louisiana 70360, United States
Johns Hopkins Hospital
Baltimore, Maryland 21287, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215, United States
University of Michigan Health Systems
Ann Arbor, Michigan 48109, United States
Detroit Medical Center Cardiovascular Institute
Detroit, Michigan 48201, United States
St. John Hospital and Medical Center
Detroit, Michigan 48236, United States
Spectrum Health Hospitals
Grand Rapids, Michigan 49503, United States
Morristown Memorial Hospital
Morristown, New Jersey 07962, United States
North Shore University Hospital/ Long Island Jewish Hospital
Manhasset, New York 11030, United States
NYU Langone Medical Center
New York, New York 10016, United States
The Mount Sinai Medical Center
New York, New York 10029, United States
Lenox Hill Hospital
New York, New York 10075, United States
St. Francis Hospital
Roslyn, New York 11576, United States
Duke University Medical Center
Durham, North Carolina 27710, United States
Wake Forest University - Baptist Medical Center
Winston-Salem, North Carolina 27157, United States
University Hospitals - Case Medical Center
Cleveland, Ohio 44106, United States
The Ohio State University Medical Center - The Richard M. Ross Heart Hospital
Columbus, Ohio 43210, United States
Riverside Methodist Hospital
Columbus, Ohio 43214, United States
Geisinger Medical Center
Danville, Pennsylvania 17822, United States
Pinnacle Health
Harrisburg, Pennsylvania 17043, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania 15213, United States
Vanderbilt University Medical Center
Nashville, Tennessee 37232, United States
Baylor Heart and Vascular Hospital
Dallas, Texas 75226, United States
Texas Heart Institute at St. Luke's Episcopal Hospital
Houston, Texas 77030, United States
The Methodist Hospital - The Methodist DeBakey Heart & Vascular Center
Houston, Texas 77030, United States
University of Vermont Medical Center
Burlington, Vermont 05458, United States
Inova Fairfax Hospital
Falls Church, Virginia 22042, United States
Providence Sacred Heart Medical Center
Spokane, Washington 99204, United States
St. Luke's Medical Center - Aurora Health Care
Milwaukee, Wisconsin 53215, United States

References and documents

Publications

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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 ↗
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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 ↗
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Oh JK, Little SH, Abdelmoneim SS, Reardon MJ, Kleiman NS, Lin G, Bach D, Gillam L, Kar B, Coselli J, Sengupta PP, Grewal K, Chang J, Chang Y, Boulware M, Adams DH, Popma JJ; CoreValve U.S. Pivotal Trial Clinical Investigators. Regression of Paravalvular Aortic Regurgitation and Remodeling of Self-Expanding Transcatheter Aortic Valve: An Observation From the CoreValve U.S. Pivotal Trial. JACC Cardiovasc Imaging. 2015 Dec;8(12):1364-1375. doi: 10.1016/j.jcmg.2015.07.012. Epub 2015 Oct 26. PubMed 26508386 ↗
Yakubov SJ, Adams DH, Watson DR, Reardon MJ, Kleiman NS, Heimansohn D, Hermiller J Jr, Hughes GC, Harrison JK, Coselli J, Diez J, Schreiber T, Gleason TG, Conte J, Deeb GM, Huang J, Oh J, Byrne T, Caskey M, Popma JJ; CoreValve United States Clinical Investigators. 2-Year Outcomes After Iliofemoral Self-Expanding Transcatheter Aortic Valve Replacement in Patients With Severe Aortic Stenosis Deemed Extreme Risk for Surgery. J Am Coll Cardiol. 2015 Sep 22;66(12):1327-34. doi: 10.1016/j.jacc.2015.07.042. PubMed 26383718 ↗
Arnold SV, Reynolds MR, Wang K, Magnuson EA, Baron SJ, Chinnakondepalli KM, Reardon MJ, Tadros PN, Zorn GL, Maini B, Mumtaz MA, Brown JM, Kipperman RM, Adams DH, Popma JJ, Cohen DJ; CoreValve US Pivotal Trial Investigators. Health Status After Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis at Increased Surgical Risk: Results From the CoreValve US Pivotal Trial. JACC Cardiovasc Interv. 2015 Aug 17;8(9):1207-1217. doi: 10.1016/j.jcin.2015.04.018. PubMed 26292584 ↗
Reardon MJ, Adams DH, Kleiman NS, Yakubov SJ, Coselli JS, Deeb GM, 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, Qiao H, Popma JJ. 2-Year Outcomes in Patients Undergoing Surgical or Self-Expanding Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2015 Jul 14;66(2):113-21. doi: 10.1016/j.jacc.2015.05.017. Epub 2015 Jun 5. PubMed 26055947 ↗
Osnabrugge RL, Arnold SV, Reynolds MR, Magnuson EA, Wang K, Gaudiani VA, Stoler RC, Burdon TA, Kleiman N, Reardon MJ, Adams DH, Popma JJ, Cohen DJ; CoreValve U.S. Trial Investigators. Health status after transcatheter aortic valve replacement in patients at extreme surgical risk: results from the CoreValve U.S. trial. JACC Cardiovasc Interv. 2015 Feb;8(2):315-323. doi: 10.1016/j.jcin.2014.08.016. PubMed 25700755 ↗
Reardon MJ, Adams DH, Coselli JS, Deeb GM, Kleiman NS, Chetcuti S, Yakubov SJ, Heimansohn D, Hermiller J Jr, Hughes GC, Harrison JK, Khabbaz K, Tadros P, Zorn GL 3rd, Merhi W, Heiser J, Petrossian G, Robinson N, Maini B, Mumtaz M, Lee JS, Gleason TG, Resar J, Conte J, Watson D, Chenoweth S, Popma JJ; CoreValve US Clinical Investigators. Self-expanding transcatheter aortic valve replacement using alternative access sites in symptomatic patients with severe aortic stenosis deemed extreme risk of surgery. J Thorac Cardiovasc Surg. 2014 Dec;148(6):2869-76.e1-7. doi: 10.1016/j.jtcvs.2014.07.020. Epub 2014 Jul 30. PubMed 25152474 ↗
Adams DH, Popma JJ, Reardon MJ, Yakubov SJ, Coselli JS, Deeb GM, Gleason TG, Buchbinder M, Hermiller J Jr, Kleiman NS, Chetcuti S, Heiser J, Merhi W, Zorn G, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Conte J, Maini B, Mumtaz M, Chenoweth S, Oh JK; U.S. CoreValve Clinical Investigators. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014 May 8;370(19):1790-8. doi: 10.1056/NEJMoa1400590. Epub 2014 Mar 29. PubMed 24678937 ↗
Popma JJ, Adams DH, Reardon MJ, Yakubov SJ, Kleiman NS, Heimansohn D, Hermiller J Jr, Hughes GC, Harrison JK, Coselli J, Diez J, Kafi A, Schreiber T, Gleason TG, Conte J, Buchbinder M, Deeb GM, Carabello B, Serruys PW, Chenoweth S, Oh JK; CoreValve United States Clinical Investigators. Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery. J Am Coll Cardiol. 2014 May 20;63(19):1972-81. doi: 10.1016/j.jacc.2014.02.556. Epub 2014 Mar 19. PubMed 24657695 ↗

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Dec 2010 to primary completion in Aug 2014, 44 months.

Results were first posted in Jun 2015, 10 months after primary completion.

Of 103 industry-sponsored interventional studies with no phase under Aortic Valve Stenosis, half reached primary completion within 29 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 56. This study's 44 months is above that.

Counting every sponsor, half of 277 studies reached it within 33 months; a quarter within 19 and three quarters within 72.

How these figures are worked out, and which studies are left out of them.

Registered: Nov 10, 2010
First posted: Nov 15, 2010
StartActual: Dec 10, 2010
Primary completionActual: Aug 2014
CompletionActual: May 15, 2019
Results first posted: Jun 8, 2015
Last update: Oct 25, 2022

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Oct 25, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01240902
Lead sponsor: Medtronic Cardiovascular
Responsible party: Sponsor
First posted: Nov 15, 2010
Start date: Dec 10, 2010
Primary completion: Aug 2014
Completion: May 15, 2019
Results posted: Jun 8, 2015
Last update: Oct 25, 2022

Study contacts

David H Adams, MD

principal investigator · Icahn School of Medicine at Mount Sinai

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2022. You cannot join it, but the record below documents what was studied.

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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

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