Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01675440
Other study ID # 10050361DOC
Secondary ID
Status Active, not recruiting
Phase
First received
Last updated
Start date August 2012
Est. completion date January 2026

Study information

Verified date April 2024
Source Medtronic Cardiovascular
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

To evaluate the safety and efficacy of the Medtronic CoreValve® System for the treatment of symptomatic severe aortic stenosis in subjects with significant comorbidities in whom the risk of surgical aortic valve replacement has a predicted operative mortality or serious, irreversible morbidity risk of ≥50% at 30 days.


Description:

The primary objective of the study is to evaluate the safety and effectiveness of the Medtronic CoreValve® System (MCS) in a subset of subjects excluded from the U.S. Extreme Risk Pivotal Trial population due to one or more additional co-morbidities, as measured by a composite of all-cause death or major stroke at 12 months, in the treatment of symptomatic severe aortic stenosis in subjects necessitating aortic valve replacement. Subjects enrolled in this study have a predicted operative mortality or serious, irreversible morbidity risk of ≥50% at 30 days associated with surgical aortic valve replacement.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 782
Est. completion date January 2026
Est. primary completion date December 2016
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility Inclusion Criteria: - Subject must have co-morbidities such that one cardiologist and two cardiac surgeons agree that medical factors preclude operation, based on a conclusion that the probability of death or serious morbidity exceeds the probability of meaningful improvement. Specifically, the predicted operative risk of death or serious, irreversible morbidity is = 50% at 30 days. - Subjects must meet all of the criteria under at least one of the sub-groups 2a-c: a. Senile degenerative aortic valve stenosis and i. At least one of the following co-morbid conditions: 1. Severe (=3-4+) mitral valve regurgitation as measured by echocardiography 2. Severe (=3-4+) tricuspid valve regurgitation as measured by echocardiography 3. End-stage renal disease requiring renal replacement therapy (Stage 5 of the KDOQI CKD Classification) or creatinine clearance <20cc/min but not requiring renal replacement therapy AND ii. mean gradient > 40 mmHg or jet velocity greater than 4.0 m/sec by either resting or dobutamine stress echocardiogram (if the LVEF < 50%), or simultaneous pressure recordings at cardiac catheterization either resting or with dobutamine stress (if the LVEF < 50%) AND iii. an initial aortic valve area of = 0.8 cm2 (or aortic valve area index =0.5 cm2/m2) by resting echocardiogram or simultaneous pressure recordings at cardiac catheterization AND/OR b. Low gradient, low output aortic stenosis as defined by the presence of all three of the following i. In the presence of LVEF <50%, absence of contractile reserve, a mean gradient =25mmHg and <40mmHg AND jet velocity less than 4.0m/sec with dobutamine stress echocardiography or simultaneous pressure recordings at cardiac catheterization OR In the presence of LVEF =50%, a mean gradient =25mmHg and <40mmHg AND jet velocity less than 4.0 m/sec, by echocardiography or simultaneous pressure recordings at cardiac catheterization AND ii. an initial aortic valve area of =0.8 cm2 (or aortic valve area index =0.5 cm2/m2) by resting echocardiogram or simultaneous pressure recordings at cardiac catheterization AND iii. radiographic evidence of severe aortic valve calcification AND/OR c. Failed bioprosthetic surgical aortic valve - Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater. - The subject or the subject's legal representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site. - The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits. Exclusion Criteria: Clinical - Evidence of an acute myocardial infarction =30 days before the MCS TAVI procedure. - Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the MCS TAVI procedure - Blood dyscrasias as defined: leukopenia (WBC <1000mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy. - Untreated clinically significant coronary artery disease requiring revascularization. - Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support. - Need for emergency surgery for any reason. - Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) <20% as measured by resting echocardiogram. - Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA). - Active Gastrointestinal (GI) bleeding that would preclude anticoagulation. - A known hypersensitivity or contraindication to all anticoagulation/antiplatelet regimens (including ability to be anticoagulated for the index procedure), nitinol, or [allergic] sensitivity to contrast media which cannot be adequately pre-medicated. - Ongoing sepsis, including active endocarditis. - Subject refuses a blood transfusion. - Life expectancy <12 months due to associated non-cardiac co-morbid conditions. - Other medical, social, or psychological conditions that in the opinion of an Investigator precludes the subject from appropriate consent. - Severe dementia (resulting in either inability to provide informed consent for the study/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits). - Currently participating in an investigational drug or another device study. - Symptomatic carotid or vertebral artery disease. Anatomical Subject has a: - Native aortic annulus size <18 mm or >29 mm per the baseline diagnostic imaging (not applicable for TAV in SAV subjects) OR - Surgical bioprosthetic annulus <17mm or >29mm i. Stented SAV per the manufactured labeled inner diameter OR ii. Stentless SAV per the baseline diagnostic imaging - Subject has a pre-existing prosthetic heart valve with a rigid support structure in either the mitral or pulmonic position: 1. that could affect the implantation or function of the study valve OR 2. the implantation of the study valve could affect the function of the pre-existing prosthetic heart valve - Moderate to severe mitral stenosis. - Mixed aortic valve disease: aortic stenosis and aortic regurgitation with predominant aortic regurgitation, (AR is moderate-severe to severe (=3-4+))(except for failed surgical bioprothesis) - Hypertrophic obstructive cardiomyopathy. - Echocardiographic evidence of new or untreated intracardiac mass, thrombus or vegetation. - Severe basal septal hypertrophy with an outflow gradient. - Aortic root angulation (angle between plane of aortic valve annulus and horizontal plane/vertebrae) >70° (for femoral and left subclavian/axillary access) and >30° (for right subclavian/axillary access). - Ascending aorta that exceeds the maximum diameter for any given native or surgical bioprosthetic* aortic annulus size (see table below) Aortic Annulus Diameter/ Ascending Aorta Diameter, 18 mm* - 20 mm/ >34 mm, 20 mm - 23 mm/ >40 mm, 23 mm - 27 mm/ >43 mm, 27 mm - 29 mm/ >43 mm, * 17mm for surgical bioprosthetic aortic annulus - Congenital bicuspid or unicuspid valve verified by echocardiography (Not applicable for TAV in SAV subjects). - Sinus of valsalva anatomy that would prevent adequate coronary perfusion. - Degenerated surgical bioprothesis presents with a significant concomitant perivalvular leak (between prothesis and native annulus), is not securely fixed in the native annulus, or is not structurally intact (e.g. wireform frame fracture) (ONLY FOR TAV in SAV subjects) - Degenerated surgical bioprothesis presents with a partially detached leaflet that in the aortic position may obstruct a coronary ostium (ONLY FOR TAV in SAV subjects) Vascular - Transarterial access not able to accommodate an 18Fr sheath.

Study Design


Intervention

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


Locations

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

Sponsors (1)

Lead Sponsor Collaborator
Medtronic Cardiovascular

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary All-cause Mortality or Major stroke All-cause Mortality or Major Stroke 12 months
Secondary Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) Event Rate MACCE is defined as a composite of: • All-Cause Death • Myocardial Infarction (MI) • All Stroke • Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve) 30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary The Occurrence of individual MACCE Components Individual MACCE Components Include: - All Cause Mortality - MI - All stroke - Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve) 30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary Major Adverse Events (MAEs) MAEs Include: •MACCE •Acute Kidney Injury •Cardiac Tamponade •Prosthetic Valve Dysfunction •Cardiogenic Shock •Valve Endocarditis •Life-Threatening, Disabling or Major Bleeding •Major Vascular Complication •Cardiac Perforation •Device Migration/Valve Embolism 30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary Conduction Disturbance Requiring Permanent Pacemaker Implantation The incidence of conduction disturbance requiring permanent pacemaker implantation 30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary Change in NYHA Class Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement. 30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary Change in Distance Walked During 6-minute Walk Test (6MWT) from Baseline Change in distance walked during 6MWT from baseline 30 days and 12 months
Secondary Ratio of Days Alive Out of Hospital Versus Total Days Alive 12 months
Secondary Quality of Life (QoL) Change from Baseline QoL change from baseline using the following measures: •Kansas City Cardiomyopathy Questionnaire (KCCQ) •SF-12 •EuroQoL 30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary Echocardiographic Assessment of Valve Performance Using the following measures: • Transvalvular mean gradient • Effective orifice area (EOA) •degree of aortic valve regurgitation 30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary Aortic Valve Disease Hospitalization The number of subjects re-hospitalized after the initial procedure 30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary Cardiovascular Deaths and Valve-related Deaths The number of cardiovascular deaths and valve-related deaths 30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary Strokes The number of subjects with strokes and TIAs 30 days, 6 months, 12 months and annually thereafter up to 5 years
Secondary Index Procedure Related Major Adverse Events (MAEs) Index procedure-related MAE events will be summarized Procedure
Secondary Length of Index Procedure Hospital Stay The length of index procedure hospital stay will be summarized Number of days from admission to discharge
Secondary Device Success Defined as: 1) Successful vascular access, delivery and deployment of the device, and successful retrieval of the delivery system, 2) Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function), 3) Intended performance of the prosthetic valve (aortic valve area > 1.2 cm2 for 26, 29 and 31mm valves, = 0.9 cm2 for 23mm valve (by echocardiography using the continuity equation) and mean aortic valve gradient < 20 mmHg or peak velocity < 3 m/sec, without moderate or severe prosthetic valve aortic regurgitation) 4) Only one valve implanted in the proper anatomical location. For TAV in SAV subjects, only # 1, 2 and 4 will be used to calculate device success. Number of days from admission to discharge
Secondary Procedural Success Defined as device success and absence of in-hospital MACCE Number of days from admission to discharge
Secondary Evidence of Prosthetic Valve Dysfunction PVD was defined according to VARC using the site reported echocardiography assessments including aortic regurgitation (AR) and aortic stenosis (AS) evaluations. Total AR reported as moderate or severe was considered PVD. AS was defined as significant stenosis and considered PVD if one of the following was met: •Peak velocity > 4 m/s •Mean gradient > 35 mmHg •EOA < 0.8 cm2 •TVIV1 / TVIV2 < 0.25 30 days, 6 months, 12 months and annually thereafter up to 5 years
See also
  Status Clinical Trial Phase
Completed NCT01238497 - SOURCE XT REGISTRY
Recruiting NCT04029844 - Colibri Transcatheter Aortic Heart Valve System Study N/A
Recruiting NCT03280433 - Influence of EPICardial Adipose Tissue in HEART Diseases: EPICHEART Study N/A
Completed NCT05492383 - SAvvyWire™ EFficacy and SafEty in Transcatheter Aortic Valve Implantation Procedures (SAFE-TAVI) N/A
Active, not recruiting NCT03752866 - The CONFIDENCE Registry N/A
Completed NCT01651780 - Open-label, Randomized Trial in Patients Undergoing TAVR to Determine Safety & Efficacy of Bivalirudin vs UFH Phase 3
Recruiting NCT06173115 - Comparison of a Single Versus Double Perclose Technique for TAVR N/A
Recruiting NCT06136429 - A Prospective, Multicenter, Single-arm Study to Evaluate a Transcatheter Aortic Valve System Safety and Efficacy for the Treatment of Patients With Severe Aortic Stenosis N/A
Not yet recruiting NCT06015997 - Prevalence of ATTR Cardiac Amyloidosis in Patients Undergoing TAVR
Recruiting NCT03291925 - Primary Non-invasive Cardiac Computed Tomography Versus Routine Invasive Angiography Prior to TAVI N/A
Terminated NCT03004599 - Safety and Efficacy of SYM-SV/DS-002 in Patients With Severe Aortic Stenosis N/A
Recruiting NCT04076150 - Safety and Performance Study of the Optimum Transcatheter Aortic Valve N/A
Completed NCT01074658 - CoreValve Advance International Post Market Study N/A
Completed NCT02575768 - Myocardial Flow Reserve in Severe AS Without Obstructive Coronary Artery Disease N/A
Completed NCT01994330 - Severe Aortic Stenosis and Acquired Von Willebrand´s Disease: The Impact of Desmopressin in Valve-Replacement Surgery Phase 4
Completed NCT04286893 - Improved HRV, Inflammation Markers and Endothelial Function After TAVI
Not yet recruiting NCT06177392 - VARC-TAVI VALVE IMPLANTATION) N/A
Active, not recruiting NCT04206228 - Intravenous Iron Supplement for Iron Deficiency in Patients With Severe Aortic Stenosis Phase 2
Not yet recruiting NCT03788590 - Evaluate the Transcatheter Artificial Aortic Valve and Transcatheter Artificial Heart Values Delivery System N/A
Completed NCT01531374 - Safety and Efficacy Continued Access Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in Very High Risk Subjects and High Risk Subjects Who Need Aortic Valve Replacement N/A