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).

Severe Aortic Stenosis Clinical Trial

— SURTAVI  

Official title:

Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01586910
• Other study ID #: IDE #G120169
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 2012
• Est. completion date: November 2026

Study information

• Verified date: October 2023
• Source: Medtronic Cardiovascular
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1746
• Est. completion date: November 2026
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic
• Severe Aortic Stenosis

Intervention

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

Procedure:
• Surgical Aortic Valve Replacement (SAVR)

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiovascular

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Germany,  Netherlands,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause Mortality or Disabling Stroke Rate Expressed as a Posterior Probability	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.	24 months
Secondary	Percentage of Participants With Major Adverse Cardiovascular and Cerebrovascular Events (MACCE)	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)	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.
Secondary	Percentage of Participants With Individual MACCE Components	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)	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.
Secondary	Percentage of Participants With Major Adverse Events (MAE)	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.	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.
Secondary	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.
Secondary	Change in NYHA Class From Baseline	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.	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.
Secondary	Change in Distance Walked During 6-minute Walk Test (6MWT)	Change in distance walked during 6MWT from baseline	From baseline to 30 days, baseline to 12 months, and baseline to 24 months
Secondary	Ratio of Days Alive Out of Hospital Versus Total Days Alive		12 and 24 months
Secondary	Quality of Life (QoL) Change From Baseline	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.	Baseline, 30 days, 3 months, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete.
Secondary	Transvalvular Mean Gradient (in mmHg) as an Assessment of Prosthetic Valve Performance	Using the following measure: -Transvalvular mean gradient	discharge, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete
Secondary	Effective Orifice Area as an Assessment of Prosthetic Valve Performance	Using the following measure: -Effective Orifice Area (cm^2)	discharge, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete
Secondary	Degree of Aortic Valve Regurgitation as an Assessment of Prosthetic Valve Performance	Using the following measure: - Degree of Aortic Valve Regurgitation (Transvalvular and Paravalvular)	discharge, 6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete
Secondary	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.
Secondary	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
Secondary	Percentage of Participants With Stroke and TIAs	Strokes (of any severity) and Transient Ischemic Attacks (TIAs)	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete.
Secondary	Peri-procedural Neurological Injury	Neurological injury (stroke, TIA, or encephalopathy)	discharge or 7 days post index procedure (whichever occurred first)
Secondary	Index Procedure Related Major Adverse Events (MAEs)	Index procedure related MAEs were defined as events occurring during, or as a direct result of, the index procedure.	Procedure through 30 day visit
Secondary	Length of Index Procedure Hospital Stay		Number of days from admission to discharge (expected average of 7 days)
Secondary	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.
Secondary	Device Success (Medtronic CoreValve® System Subjects Only)	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)	Number of days from admission to discharge (expected average of 7 days)
Secondary	Procedural Success (Medtronic CoreValve® System Subjects Only)	Defined by device success and absence of in-hospital major adverse cardiovascular and cerebrovascular events (MACCE)	Number of days from admission to discharge (expected average of 7 days)
Secondary	Evidence of Prosthetic Valve Dysfunction (Medtronic CoreValve® System Subjects Only)	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	6 months, 12 months, and 24 months. Data for 3-5 years will be posted once data is complete.
Secondary	Percentage of Participants With Early Safety Endpoint	Percentage of participants with VARC II early safety composite at 30 days	30 Days
Secondary	Percentage of Participants With Clinical Efficacy (After 30 Days)	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.	6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is complete
Secondary	Percentage of Participants With Time-Related Safety	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.	30 days, 6 months, 12 months, 18 months, and 24 months. Data for 3-5 years will be posted once data is available.
Secondary	Resheath and Recapture Success (Evolut R Only)	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.	Procedure