Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI).

Not Applicable

Active, not recruiting

Conditions: Severe Aortic Stenosis

Interventions: Procedure: Surgical Aortic Valve Replacement (SAVR)
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Device: Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)

Registration Number: NCT01586910

Lead Sponsor: Medtronic Cardiovascular

Brief Summary: The purpose of the study is to investigate the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with severe, symptomatic Aortic Stenosis (AS) at intermediate surgical risk by randomizing patients to either Surgical Aortic Valve Replacement (SAVR) or TAVI with the Medtronic CoreValve® System.

Single Arm: The purpose of this trial is to evaluate the safety and effectiveness of transcatheter aortic valve implementation (TAVI) in patients with severe symptomatic Aortic Stenosis (AS) at intermediate surgical risk with TAVI. This is a non-randomized phase of the pivotal clinical trial.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 1746

Inclusion Criteria

Subject must have co-morbidities such that Heart Team agrees predicted risk of operative mortality is ≥3% and <15% at 30 days (Intermediate Clinical Risk classification). Heart team evaluation of clinical surgical mortality risk for each patient includes the calculated STS score for predicted risk of surgical mortality augmented by consideration of the overall clinical status and co-morbidities unmeasured by the STS risk calculation;
Heart Team unanimously agree on treatment proposal and eligibility for randomization* based on their clinical judgement (including anatomy assessment, risk factors, etc.);
Subject has severe aortic stenosis presenting with;
1. Critical aortic valve area defined as an initial aortic valve area of ≤1.0cm2 or aortic valve area index < 0.6cm2/m2 AND
2. Mean gradient > 40mmHg or Vmax > 4m/sec by resting echocardiogram or simultaneous pressure recordings at cardiac catherization [or with dobutamine stress, if subject has left ventricular ejection fraction (LVEF) <55%] or velocity ratio < 0.25;
Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater;
Subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits;
Subject meets the legal minimum age to provide informed consent based on local regulatory requirements;

Exclusion Criteria

Subject has refused surgical aortic valve replacement (SAVR) as a treatment option; (not applicable for Single Arm)
Any condition considered a contraindication for placement of a bioprosthetic valve (i.e., subject requires a mechanical valve);
A known hypersensitivity or contraindication to all anticoagulation/antiplatelet regimens (or inability to be anticoagulated for the index procedure), nitinol, or sensitivity to contrast media which cannot be adequately pre-medicated;
Blood dyscrasias as defined: leukopenia (WBC <1000mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy;
Ongoing sepsis, including active endocarditis;
Any condition considered a contraindication to extracorporeal assistance;
Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to randomization* (Subjects with recent placement of drug eluting stent(s) should be assessed for ability to safely proceed with SAVR within the protocol timeframe);
Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within six weeks of randomization*;
Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support;
Recent (within 6 months of randomization*) cerebrovascular accident (CVA) or transient ischemic attack (TIA);
Active gastrointestinal (GI) bleeding that would preclude anticoagulation;
Subject refuses a blood transfusion;
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);
Multivessel coronary artery disease with a Syntax score >22 and/or unprotected left main coronary artery (Syntax score calculation is not required for patients with history of previous revascularization if repeat revascularization is not planned);
Estimated life expectancy of less than 24 months due to associated non-cardiac comorbid conditions;
Other medical, social, or psychological conditions that in the opinion of the Investigator precludes the subject from appropriate consent or adherence to the protocol required follow-up exams;
Currently participating in an investigational drug or another device trial (excluding registries);
Evidence of an acute myocardial infarction ≤30 days before the index procedure;
Need for emergency surgery for any reason;
True porcelain aorta (i.e. Heart Team agrees the aorta is not clampable for SAVR);
Extensive mediastinal radiation;
Liver failure (Child-C);
Reduced ventricular function with left ventricular ejection fraction (LVEF) <20% as measured by resting echocardiogram;
Uncontrolled atrial fibrillation (e.g. resting heart rate > 120 bpm);
Pregnancy or intent to become pregnant prior to completion of all protocol follow-up requirements;
End stage renal disease requiring chronic dialysis or creatinine clearance < 20 cc/min;
Pulmonary Hypertension (systolic pressure> 80mmHg);
Severe Chronic Obstructive Pulmonary Disease (COPD) demonstrated by Forced Expiratory Volume (FEV1) < 750cc;
Frailty assessments identify:
1. Subject is < 80 years of age and three or more of the following apply
2. Subject is ≥ 80 years of age and two or more of the following apply
  - Wheelchair bound
  - Resides in an institutional care facility (e.g., nursing home, skilled care center)
  - Body Mass Index < 20 kg/m2
  - Grip Strength < 16 kg
  - Katz Index Score ≤ 4
  - Albumin < 3.5 g/dL;
Marfan syndrome or other known connective tissue disease that would necessitate aortic root replacement/intervention; (Not applicable for Single Arm)

Note: Additional anatomical and vascular exclusion criteria may apply.

Note: * For purposes of the single arm phase of the trial, "randomization" will refer to trial enrollment.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Medtronic CoreValve® System TAVI	Medtronic CoreValve® Evolut R System Transcatheter Aortic Valve Implantation (TAVI)	Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
SAVR	Surgical Aortic Valve Replacement (SAVR)	Surgical Aortic Valve Replacement (SAVR)
Medtronic CoreValve® System TAVI	Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)	Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Primary Outcome Measures

Name	Time	Method
All-cause Mortality or Disabling Stroke Rate Expressed as a Posterior Probability	24 months	All-cause mortality: all deaths from any cause after valve intervention. This includes all cardiovascular and non-cardiovascular deaths. Disabling Stroke: a modified rankin (mRS) score of 2 or more at 90 days and an increase in at least one mRS category from an individual's pre-strike baseline.

Secondary Outcome Measures

Name	Time	Method
Index Procedure Related Major Adverse Events (MAEs)	Procedure through 30 day visit	Index procedure related MAEs were defined as events occurring during, or as a direct result of, the index procedure.
Change in NYHA Class From Baseline	Baseline to 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.	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.
Percentage of Participants With Individual MACCE Components	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.	MACCE is defined as a composite of: * All-cause death * Myocardial infarction (MI) * All stroke, and * Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)
Change in Distance Walked During 6-minute Walk Test (6MWT)	From baseline to 30 days, baseline to 12 months, and baseline to 24 months	Change in distance walked during 6MWT from baseline
Percentage of Participants With Major Adverse Cardiovascular and Cerebrovascular Events (MACCE)	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.	MACCE is defined as a composite of: * All-cause death * Myocardial infarction (MI) * All stroke, and * Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)
Percentage of Participants With Conduction Disturbance Requiring Permanent Pacemaker Implantation	30 day, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.
Percentage of Participants With Major Adverse Events (MAE)	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.	Major Adverse Events (MAE) include all death, MI, all stroke, reintervention, cardiac perforation, cardiac tamponade, cardiogenic shock, valve malpositioning, prosthetic valve dysfunction, acute kidney injury, major vascular complication, life threatening or disabling bleed, major bleed, and valve endocarditis.
Ratio of Days Alive Out of Hospital Versus Total Days Alive	12 and 24 months
Percentage of Participants With Clinical Efficacy (After 30 Days)	6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete	Combined clinical efficacy after 30 days was defined as the composite of all-cause mortality, all strokes (disabling and non-disabling), hospitalization for valve-related symptoms or worsening congestive heart failure, NYHA III or IV, and valve-related dysfunction.
Transvalvular Mean Gradient (in mmHg) as an Assessment of Prosthetic Valve Performance	discharge, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete	Using the following measure: -Transvalvular mean gradient
Presence of Atrial Fibrillation	post-procedure, discharge, 30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.
Percentage of Participants With Cardiovascular Deaths and Valve-Related Deaths	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete
Procedural Success (Medtronic CoreValve® System Subjects Only)	Number of days from admission to discharge (expected average of 7 days)	Defined by device success and absence of in-hospital major adverse cardiovascular and cerebrovascular events (MACCE)
Evidence of Prosthetic Valve Dysfunction (Medtronic CoreValve® System Subjects Only)	6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete.	Prosthetic Valve Dysfunction (PVD) was defined according to Valve Academic Research Consortium (VARC) II using the Core Lab Echocardiography assessments including aortic regurgitation (AR) and aortic stenosis (AS) evaluations. Total aortic regurgitation (AR) reported as moderate or severe was considered PVD defined as: * Mean aortic valve gradient ≥20 mmHg AND ((EOA ≤0.9 cm2 if BSA \<1.6 or ≤1.1 cm2 if BSA ≥1.6) OR DVI \<0. 35 m/s) OR * moderate or severe total AR
Percentage of Participants With Time-Related Safety	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is available.	The VARC II time-related valve safety composite was defined as the rate of valve-related dysfunction (mean aortic valve gradient ≥ 20 mm Hg, EOA ≤ 0.9-1.1 cm2 depending on body surface area and/or DVI \<0.35, AND/ OR moderate or severe prosthetic valve regurgitation), aortic valve reintervention, prosthetic valve endocarditis, prosthetic valve thrombosis, thromboembolic events, and VARC II bleeding events.
Quality of Life (QoL) Change From Baseline	Baseline, 30 days, 3 months, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete.	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. * 36 Item Short Form Health Survey (SF-36): 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.
Effective Orifice Area as an Assessment of Prosthetic Valve Performance	discharge, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete	Using the following measure: -Effective Orifice Area (cm\^2)
Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance	discharge, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete	Using the following measure: - Degree of Aortic Valve Regurgitation (Transvalvular and Paravalvular)
Percentage of Participants With Aortic Valve Disease Related Hospitalizations	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.
Percentage of Participants With Stroke and TIAs	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.	Strokes (of any severity) and Transient Ischemic Attacks (TIAs)
Peri-procedural Neurological Injury	discharge or 7 days post index procedure (whichever occurred first)	Neurological injury (stroke, TIA, or encephalopathy)
Length of Index Procedure Hospital Stay	Number of days from admission to discharge (expected average of 7 days)
Device Success (Medtronic CoreValve® System Subjects Only)	Number of days from admission to discharge (expected average of 7 days)	* Absence of procedural mortality * Correct positioning of a single prosthetic heart valve into the proper anatomical location * Intended performance of the prosthetic heart valve (no prosthesis-patient mismatch and mean aortic valve gradient \<20 mmHg or peak velocity \<3 m/s, AND no moderate or severe prosthetic valve regurgitation)
Percentage of Participants With Early Safety Endpoint	30 Days	Percentage of participants with VARC II early safety composite at 30 days
Resheath and Recapture Success (Evolut R Only)	Procedure	The Evolut™ R system provides operators with the ability to resheath or recapture the valve before it is completely deployed in the event of initial suboptimal positioning. Successful resheath was defined as successfully retrieving a portion of the valve into the capsule of the delivery catheter, and successful recapture was defined as successfully recapturing the entirety of the valve into the capsule of the delivery catheter.

Trial Locations

Locations (86): Stern Cardiovascular
🇺🇸
Memphis, Tennessee, United States
Southern California Permenente Medical Group
🇺🇸
Pasadena, California, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
Yale New Haven Hospital
🇺🇸
New Haven, Connecticut, United States
Washington Hospital Center
🇺🇸
Washington, District of Columbia, United States
Morton Plant Hospital
🇺🇸
Clearwater, Florida, United States
Keck Medical Center of USC
🇺🇸
Los Angeles, California, United States
El Camino Hospital
🇺🇸
Mountain View, California, United States
Delray Medical Center
🇺🇸
Delray Beach, Florida, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
Piedmont Healthcare, Inc.
🇺🇸
Atlanta, Georgia, United States
North Shore University Hospital
🇺🇸
Manhasset, New York, United States
The OhioHealth Research Institute
🇺🇸
Columbus, Ohio, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
University of Pennsylvania Health System
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Baylor Heart and Vascular Hospital
🇺🇸
Dallas, Texas, United States
Sunnybrook Research Institute
🇨🇦
Toronto, Ontario, Canada
Toronto General Hospital (University Health Network)
🇨🇦
Toronto, Ontario, Canada
St. Vincent Heart Center of Indiana
🇺🇸
Indianapolis, Indiana, United States
Good Samaritan Hospital
🇺🇸
Cincinnati, Ohio, United States
The Methodist DeBakey Heart & Vascular Center
🇺🇸
Houston, Texas, United States
University of Kansas Hospital
🇺🇸
Kansas City, Kansas, United States
The Ohio State University
🇺🇸
Columbus, Ohio, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Bern University Hospital
🇨🇭
Bern, Switzerland
The Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
University of Miami
🇺🇸
Coral Gables, Florida, United States
Universitatsspital Zurich
🇨🇭
Zurich, Switzerland
Banner Good Samaritan Medical Center
🇺🇸
Phoenix, Arizona, United States
Detroit Medical Center
🇺🇸
Detroit, Michigan, United States
Henry Ford
🇺🇸
Detroit, Michigan, United States
St. John Hospital & Medical Center
🇺🇸
Detroit, Michigan, United States
Mayo Clinic - St. Mary's Hospital
🇺🇸
Rochester, Minnesota, United States
Abbott NW - MN Heart Institute Foundation
🇺🇸
Minneapolis, Minnesota, United States
Alegent Creighton Health Research Center
🇺🇸
Omaha, Nebraska, United States
Oklahoma Heart Institute
🇺🇸
Oklahoma City, Oklahoma, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Aurora St. Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
University of Michigan Health Systems
🇺🇸
Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Cedars-Sinai Medical Center
🇺🇸
Hollywood, California, United States
Scripps Green Hospital
🇺🇸
La Jolla, California, United States
Stanford University Medical Center
🇺🇸
Stanford, California, United States
VA Palo Alto Health Care System
🇺🇸
Palo Alto, California, United States
Iowa Heart Center / Mercy Medical Center
🇺🇸
West Des Moines, Iowa, United States
Loyola University of Chicago
🇺🇸
Maywood, Illinois, United States
Cardiovascular Institute of the South
🇺🇸
Houma, Louisiana, United States
Beth Israel Deaconess Medical Center, Inc.
🇺🇸
Boston, Massachusetts, United States
Spectrum Health Hospitals
🇺🇸
Grand Rapids, Michigan, United States
Saint Luke's Hospital/MAHI
🇺🇸
Kansas City, Missouri, United States
New York University School of Medicine
🇺🇸
New York, New York, United States
Morristown Medical Center
🇺🇸
Morristown, New Jersey, United States
Cooper University Hospital
🇺🇸
Camden, New Jersey, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Winthrop University Hospital
🇺🇸
Mineola, New York, United States
Mount Sinai School of Medicine
🇺🇸
New York, New York, United States
Carolinas HealthCare System
🇺🇸
Charlotte, North Carolina, United States
Lenox Hill Hospital
🇺🇸
New York, New York, United States
St. Francis Hospital
🇺🇸
Roslyn, New York, United States
University Hospitals Case Medical Center
🇺🇸
Cleveland, Ohio, United States
Pinnacle Health Cardiovascular Institute
🇺🇸
Wormleysburg, Pennsylvania, United States
Medisch Centrum Leeuwarden
🇳🇱
Leeuwarden, Netherlands
Intermountain Medical Center
🇺🇸
Murray, Utah, United States
The Heart Hospital - Baylor Plano
🇺🇸
Plano, Texas, United States
Bon Secours St. Mary's Hospital
🇺🇸
Richmond, Virginia, United States
Sentara Cardiovascular
🇺🇸
Norfolk, Virginia, United States
London Health Sciences Centre, University Hospital
🇨🇦
London, Ontario, Canada
McGill University Health Center - Royal Victoria Hospital
🇨🇦
Montreal, Quebec, Canada
Montreal Heart Institute
🇨🇦
Montreal, Canada
Rigshospitalet
🇩🇰
Copenhagen, Denmark
Universitätsklinikum Bonn
🇩🇪
Bonn, Germany
Universitäts-Herzzentrum Freiburg • Bad Krozingen
🇩🇪
Bad Krozingen, Germany
Deutsches Herzzentrum Muenchen
🇩🇪
Munich, Germany
Servicio de Cardiologia del Hospital Virgen de la Victoria
🇪🇸
Malaga, Spain
Amphia Hospital Breda
🇳🇱
Breda, Netherlands
Erasmus Medical Center - Rotterdam
🇳🇱
Rotterdam, Netherlands
St. Antonius Hospital, R & D Cardiology
🇳🇱
Nieuwegein, Netherlands
Hospital Universitario Central de Asturias
🇪🇸
Oviedo, Spain
Karolinska Universitetssjukhuset Stockholm
🇸🇪
Stockholm, Sweden
Leeds General Infirmary
🇬🇧
Leeds, United Kingdom
Glenfield Hospital, Leicester, UK
🇬🇧
Leicester, United Kingdom
St. George's Hospital London
🇬🇧
London, United Kingdom
The Queen's Medical Center
🇺🇸
Honolulu, Hawaii, United States
University of Vermont
🇺🇸
Burlington, Vermont, United States