Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients

Not Applicable

Active, not recruiting

Conditions: Aortic Valve Stenosis

Interventions: Device: Surgical Aortic Valve Replacement (SAVR)
Device: Medtronic Transcatheter Aortic Valve Replacement Systems

Registration Number: NCT02701283

Lead Sponsor: Medtronic Cardiovascular

Brief Summary: The study objective is to demonstrate that the safety and effectiveness of the Medtronic TAVR system as measured by rates of all-cause mortality or disabling stroke at two years is noninferior to SAVR in the treatment of severe aortic stenosis in subjects who have a low predicted risk of operative mortality for SAVR.

The purpose of the expanded use addendum to the Medtronic TAVR in Low Risk Patients Trial protocol is to conclude the randomized phase of the trial and initiate the single-arm, non-randomized, continued access phase of the trial.

Detailed Description: Multi-center, international, prospective, randomized, interventional, pre-market.

Subjects will be randomized on 1:1 basis to either TAVR with the Medtronic TAVR system or to SAVR. Patients will be seen at pre and post-procedure, discharge, 30 days, 6 months, 1 year, 18 months, and annually through 10 years.

The expanded use addendum is a multi-center, prospective, non-randomized continued access trial. All heart team approved subjects will be assigned to TAVR with the Medtronic TAVR system. Patients will be seen at pre and post-procedure, discharge, 30 days, and annually through 10 years. Enrollment is expected not to exceed 3660 attempted implants in the United States.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 2223

Inclusion Criteria

Severe aortic stenosis, defined as follows:
1. For symptomatic patients:
  
  Aortic valve area ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), OR mean gradient ≥40 mmHg, OR Maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest
2. For asymptomatic patients:
  - Very severe aortic stenosis with an aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND maximal aortic velocity ≥5.0 m/sec , or mean gradient ≥60 mmHg by transthoracic echocardiography at rest, OR
  - Aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND a mean gradient ≥40 mmHg or maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest, AND an exercise tolerance test that demonstrates a limited exercise capacity, abnormal BP response, or arrhythmia OR
  - Aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND mean gradient ≥40 mmHg, or maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest, AND a left ventricular ejection fraction <50%.
Documented heart team agreement of low risk for SAVR, where low risk is defined as predicted risk of mortality for SAVR <3% at 30 days per multidisciplinary local heart team assessment.
The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

Exclusion Criteria

Any condition considered a contraindication for placement of a bioprosthetic valve (eg, subject is indicated for mechanical prosthetic valve).
A known hypersensitivity or contraindication to any of the following that cannot be adequately pre-medicated:
1. aspirin or heparin (HIT/HITTS) and bivalirudin
2. ticlopidine and clopidogrel
3. Nitinol (titanium or nickel)
4. contrast media
Blood dyscrasias as defined: leukopenia (WBC <1000 mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
Ongoing sepsis, including active endocarditis.
Any percutaneous coronary or peripheral interventional procedure with a bare metal stent within 30 days prior to randomization, or drug eluting stent performed within 180 days prior to randomization.
Multivessel coronary artery disease with a Syntax score >22 and/or unprotected left main coronary artery.
Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 10 weeks of Heart Team assessment.
Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
Recent (within 2 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
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).
Estimated life expectancy of less than 24 months due to associated non-cardiac co-morbid 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 trial procedure due to unstable coronary artery disease (WHO criteria).
Need for emergency surgery for any reason.
Subject is pregnant or breast feeding.
Subject is less than legal age of consent, legally incompetent, or otherwise vulnerable
Pre-existing prosthetic heart valve in any position.
Severe mitral regurgitation amenable to surgical replacement or repair.
Severe tricuspid regurgitation amenable to surgical replacement or repair.
Moderate or severe mitral stenosis amenable to surgical replacement or repair.
Hypertrophic obstructive cardiomyopathy with left ventricular outflow gradient.
Bicuspid aortic valve verified by echocardiography, MDCT, or MRI.
Prohibitive left ventricular outflow tract calcification.
Sinus of Valsalva diameter unsuitable for placement of the self-expanding bioprosthesis.
Aortic annulus diameter of <18 or >30 mm.
Significant aortopathy requiring ascending aortic replacement.

For transfemoral or transaxillary (subclavian) access:
Access vessel mean diameter <5.0 mm for Evolut 23R, 26R, or 29R mm TAV, or access vessel mean diameter <5.5 mm for Evolut 34R mm or Evolut PRO TAV. However, for transaxillary (subclavian) access in patients with a patent LIMA, access vessel mean diameter <5.5mm for Evolut 23R, 26R, or 29R mm TAV, or access vessel mean diameter <6.0 mm for the Evolut 34R or Evolut PRO TAV.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Surgical Aortic Valve Replacement (SAVR)	Surgical Aortic Valve Replacement (SAVR)	Treatment of Aortic Stenosis with commercial Surgical Aortic Valve Replacement (SAVR)
Medtronic Transcatheter Aortic Valve Replacement Systems	Medtronic Transcatheter Aortic Valve Replacement Systems	Treatment of Aortic Stenosis with the Medtronic CoreValve System Transcatheter Aortic Valve Implantation (TAVI) device or the Medtronic Corevalve Evolut R System Transcatheter Aortic Valve Implantation (TAVI)

Primary Outcome Measures

Name	Time	Method
Safety: All Cause Mortality or Disabling Stroke Rate at 24 Months, Randomized Controlled Trial Safety: All Cause Mortality or All Stroke Rate at 12 Months, Continued Access Study	Randomized Controlled Trial - 24 months Continued Access Study - 12 months	Assessment of procedural safety by: All-cause mortality: all deaths from any cause after valve intervention. This includes all cardiovascular and non-cardiovascular deaths. Disabling stroke: a modified rankin score (mRS) of 2 or more at 90 days post-stroke and an increase of at least one mRS category from an individual's pre-stroke baseline. All stroke: any stroke after valve intervention (ischemic, hemorrhagic, or undetermined stroke).

Secondary Outcome Measures

Name	Time	Method
New Pacemaker Implantation at 30 Days	30 days	The rate of new permanent pacemaker implant at 30 days
All Stroke (Disabling and Non-disabling) at 1 Year	1 year	The rate of all stroke (disabling and non-disabling) at 1 year
Life-threatening Bleeding at 1 Year	1 year	The rate of life-threatening bleeding at 1 year
Valve-related Dysfunction (Moderate or Severe Stenosis or Regurgitation) at 1 Year, Randomized Controlled Trial	1 year	Stenosis (moderate or severe) Any of the following: 1. Peak aortic velocity \>4 m/s OR mean aortic gradient \>40 mmHg, AND EOA \<0.8 cm2 2. Peak aortic velocity \>4 m/s OR mean aortic gradient \>40 mmHg, AND EOA ≥0.8 cm2, and DVI \<0.25 3. Peak aortic velocity ≤4 m/s and mean aortic gradient ≤ 40 mmHg, AND EOA \<0.8 cm2, and DVI \<0.25 Regurgitation (moderate or severe) Any of the following: 1. Moderate or Severe Total Regurgitation 2. Moderate or Severe Paravalvular Regurgitation 3. Moderate or Severe Transvalvular Regurgitation
Prosthetic Valve Endocarditis at 1 Year	1 year	The rate of prosthetic valve endocarditis at 1 year
Prosthetic Valve Thrombosis at 1 Year	1 year	The rate of prosthetic valve thrombosis at 1 year
RCT: Composite of Death, Disabling Stroke, Life-threatening Bleed, Major Vascular Complication, or AKI (II or III) at 30 Days CAS: Composite of Death, All Stroke, Life-threatening Bleed, or Major Vascular Complication at 30 Days	30 days	Randomized Controlled Trial: Combined clinical efficacy after 30 days was defined as the composite of all-cause mortality, disabling stroke, life-threatening bleed, major vascular complication, or AKI (II or III) Continued Access Study: Combined clinical efficacy after 30 days was defined as the composite of all-cause mortality, all stroke, life-threatening bleed, or major vascular complication
Valve-related Dysfunction Requiring Repeat Procedure at 1 Year	1 year	The rate of valve-related dysfunction requiring repeat procedure at 1 year
Repeat Hospitalization for Aortic Valve Disease at 1 Year, Randomized Controlled Trial	1 year	The rate of repeat hospitalization for aortic valve disease at 1 year
Randomized Controlled Trial - Health-related Quality of Life as Assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30 Days and 1 Year Continued Access Study - Health-related Quality of Life as Assessed by KCCQ at 1 Year	Randomized Controlled Trial - 30 days and 1 year Continued Access Study - 1 year	Quality of life summary scores and change from baseline using the following measures: 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.

Trial Locations

Locations (87): Abrazo Arizona Heart Hospital
🇺🇸
Phoenix, Arizona, United States
Scripps Memorial Hospital La Jolla
🇺🇸
La Jolla, California, United States
University of Southern California University Hospital
🇺🇸
Los Angeles, California, United States
El Camino Hospital
🇺🇸
Mountain View, California, United States
Mercy General Hospital
🇺🇸
Sacramento, California, United States
Los Robles Hospital & Medical Center
🇺🇸
Thousand Oaks, California, United States
University of Colorado Hospital
🇺🇸
Aurora, Colorado, United States
Yale New Haven Hospital
🇺🇸
New Haven, Connecticut, United States
Morton Plant Hospital
🇺🇸
Clearwater, Florida, United States
Delray Medical Center
🇺🇸
Delray Beach, Florida, United States
HealthPark Medical Center
🇺🇸
Fort Myers, Florida, United States
University of Miami Hospital
🇺🇸
Miami, Florida, United States
Tallahassee Research Institute, Inc.
🇺🇸
Tallahassee, Florida, United States
Piedmont Atlanta Hospital
🇺🇸
Atlanta, Georgia, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Saint Vincent Heart Center of Indiana
🇺🇸
Indianapolis, Indiana, United States
Mercy Medical Center
🇺🇸
Des Moines, Iowa, United States
The University of Kansas Hospital
🇺🇸
Kansas City, Kansas, United States
Jewish Hospital
🇺🇸
Louisville, Kentucky, United States
Terrebonne General Medical Center
🇺🇸
Houma, Louisiana, United States
University of Maryland Medical Center
🇺🇸
Baltimore, Maryland, United States
MedStar Union Memorial Hospital
🇺🇸
Baltimore, Maryland, United States
The Johns Hopkins Hospital
🇺🇸
Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Clinique Pasteur
🇫🇷
Toulouse, France
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Baystate Medical Center
🇺🇸
Springfield, Massachusetts, United States
University of Michigan Health System
🇺🇸
Ann Arbor, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
Spectrum Health Hospitals
🇺🇸
Grand Rapids, Michigan, United States
Abbott Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Mercy Hospital
🇺🇸
Springfield, Missouri, United States
Saint Francis Hospital
🇺🇸
East Hills, New York, United States
Saint Joseph's Hospital Health Center
🇺🇸
Liverpool, New York, United States
Northwell Health
🇺🇸
Manhasset, New York, United States
The Mount Sinai Hospital
🇺🇸
New York, New York, United States
Strong Memorial Hospital
🇺🇸
Rochester, New York, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Wake Forest Baptist Medical Center
🇺🇸
Winston-Salem, North Carolina, United States
Sanford Medical Center
🇺🇸
Fargo, North Dakota, United States
Good Samaritan Hospital
🇺🇸
Cincinnati, Ohio, United States
University Hospitals Case Medical Center
🇺🇸
Cleveland, Ohio, United States
The Ohio State University
🇺🇸
Columbus, Ohio, United States
OhioHealth Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
Integris Baptist Medical Center
🇺🇸
Oklahoma City, Oklahoma, United States
Oregon Health Science University
🇺🇸
Portland, Oregon, United States
Lehigh Valley Hospital
🇺🇸
Allentown, Pennsylvania, United States
Geinsinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Pinnacle Health
🇺🇸
Harrisburg, Pennsylvania, United States
University of Pittsburgh Medical Center UPMC Presbyterian
🇺🇸
Pittsburgh, Pennsylvania, United States
Paramount Heart
🇺🇸
Villanova, Pennsylvania, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Baylor Jack and Jane Hamilton Heart and Vascular Hospital
🇺🇸
Dallas, Texas, United States
Baylor Saint Luke's Medical Center
🇺🇸
Houston, Texas, United States
Houston Methodist Hospital
🇺🇸
Houston, Texas, United States
Methodist Hospital San Antonio
🇺🇸
San Antonio, Texas, United States
University Hospital Salt Lake City Utah
🇺🇸
Salt Lake City, Utah, United States
The University of Vermont Medical Center
🇺🇸
Burlington, Vermont, United States
Saint Mary's Hospital
🇺🇸
Richmond, Virginia, United States
Swedish Medical Center
🇺🇸
Seattle, Washington, United States
Aurora Saint Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Saint Vincent's Hospital Sydney
🇦🇺
Darlinghurst, New South Wales, Australia
Royal North Shore Hospital
🇦🇺
St Leonards, New South Wales, Australia
Monash Health
🇦🇺
Clayton, Victoria, Australia
The Alfred Hospital
🇦🇺
Melbourne, Victoria, Australia
Fiona Stanley Hospital (FSH)
🇦🇺
Murdoch, Western Australia, Australia
London Health Sciences Centre
🇨🇦
London, Ontario, Canada
Toronto General Health Hospital
🇨🇦
Toronto, Ontario, Canada
Glen Royal Victoria (McGill)
🇨🇦
Montréal, Quebec, Canada
Montreal Heart
🇨🇦
Montréal, Canada
IUCPQ
🇨🇦
Quebec, Canada
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Canada
Centre Hospitalier Régional Universitaire de Lille
🇫🇷
Lille, France
L'Hôpital Privé Jacques Cartier Massy
🇫🇷
Massy, France
Kokura Memorial Hospital
🇯🇵
Kitakyushu, Fokuoka, Japan
Sapporo Higashi Tokushukai Hospital
🇯🇵
Sapporo, Hokkaido, Japan
Teikyo University Hospital
🇯🇵
Tokyo, Itabashi-Ku, Japan
Shonan Kamakura General Hospital
🇯🇵
Kamakura, Kanagawa, Japan
Sendai Kousei Hospital
🇯🇵
Sendai, Miyagi, Japan
National Cerebral and Cardiovasclular Center
🇯🇵
Suita, Osaka, Japan
The University of Osaka Hospital
🇯🇵
Suita, Osaka, Japan
Sakakibara Heart Institute
🇯🇵
Fuchu, Tokyo, Japan
Catharina Ziekenhuis
🇳🇱
Eindhoven, Netherlands
St. Antonius Hospital Nieuwegein
🇳🇱
Nieuwegein, Netherlands
Erasmus Medisch Centrum
🇳🇱
Rotterdam, Netherlands
Waikato Hospital
🇳🇿
Hamilton, New Zealand