EARLY TAVR: Evaluation of TAVR Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis (EARLY TAVR)

Evaluation of Transcatheter Aortic Valve Replacement Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis

This study will evaluate the safety and effectiveness of the Edwards SAPIEN 3/SAPIEN 3 Ultra Transcatheter Heart Valve (THV) compared with clinical surveillance (CS) in asymptomatic patients with severe, calcific aortic stenosis.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Diseases; Aortic Stenosis, Severe
• Intervention / Treatment: Device: Edwards SAPIEN 3 / SAPIEN 3 Ultra THV

Detailed Description

This is a prospective, randomized, controlled, multicenter study. Patients will be randomized to receive either transcatheter aortic valve replacement (TAVR) with the Edwards SAPIEN 3 / SAPIEN 3 Ultra THV or clinical surveillance. Patients will be stratified by whether they are able to perform a treadmill stress test. Patients who have a positive stress test will be followed in a registry to collect data on subsequent treatment and mortality, as applicable.

• Study Type: Interventional
• Enrollment (Actual): 901
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada, M5G2C4
      • Toronto General Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center
  • California
    • Burlingame, California, United States, 94010
      • Mills Peninsula Health Services
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
    • Pasadena, California, United States, 91105
      • Huntington Hospital
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Francisco, California, United States, 94115
      • Kaiser San Francisco Medical Center
    • Stanford, California, United States, 94305
      • Stanford Hospital and Clinics Palo Alto
  • Colorado
    • Loveland, Colorado, United States, 80538
      • UC Health Northern Colorado (Medical Center of the Rockies)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center DC
  • Florida
    • Gainesville, Florida, United States, 32605
      • The Cardiac & Vascular Institute Research Foundation
    • Gainesville, Florida, United States, 32615
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center Chicago
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem Research Institution
    • Lisle, Illinois, United States, 60532
      • Alexian Brothers Hospital Network
    • Springfield, Illinois, United States, 62701
      • Prairie Education and Research Cooperative
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
    • West Des Moines, Iowa, United States, 50266
      • Iowa Heart Center
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Cardiovascular Research Institute of Kansas
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Hyannis, Massachusetts, United States, 02601
      • Cape Cod Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Heart
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City Mid America
  • Montana
    • Missoula, Montana, United States, 59802
      • St. Patrick Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Mary Hitchcock Memorial Hospital
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System Hospital Corp - Morristown Medical Center
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
    • Piscataway, New Jersey, United States, 08854
      • Rutgers Robert Wood Johnson Medical School
  • New York
    • Albany, New York, United States, 12211
      • Albany Medical College
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Buffalo, New York, United States, 14203
      • University at Buffalo - Kaleida Health
    • Mineola, New York, United States, 11501
      • NYU Langone Hosptial - Long Island
    • New York, New York, United States, 10065
      • Cornell University
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center/ New York Presbyterian Hospital
    • Rochester, New York, United States, 14621
      • Rochester General Hospital
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolina's Health System
    • Raleigh, North Carolina, United States, 27607
      • NC Heart and Vascular (Rex Hospital)
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital, Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43213
      • Mount Carmel Health System
    • Columbus, Ohio, United States, 43214
      • The Ohio Health Research Institute
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Kaiser Portland
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17101
      • Pinnacle Health
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny - Singer Research Institute
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
    • York, Pennsylvania, United States, 17403
      • York Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75093
      • The Heart Hospital Baylor Plano
    • Dallas, Texas, United States, 75231
      • Texas Health Physician Group
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center Salt Lake City
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Heart and Vascular Institute (Fairfax Inova)
    • Norfolk, Virginia, United States, 23507
      • Sentara Cardiovascular Research Institute
    • Roanoke, Virginia, United States, 24014
      • Carilion Medical Center
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Everett
    • Seattle, Washington, United States, 98195
      • University of Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
    • Spokane, Washington, United States, 99204
      • Sacred Heart Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • CAMC Clinical Trials Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 65 years of age or older
2. Severe aortic stenosis
3. Patient is asymptomatic
4. LV ejection fraction ≥ 50%
5. Society of Thoracic Surgeons (STS) risk score ≤ 10
6. The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.

Exclusion Criteria:

1. Patient is symptomatic
2. Patient has any concomitant valvular, aortic, coronary artery disease requiring surgery making AVR a Class I indication.
3. Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm THV
4. Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath.
5. Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post TAVR
6. Evidence of an acute myocardial infarction ≤ 30 days before randomization
7. Aortic valve is unicuspid, bicuspid with unfavorable features for TAVR, or is non-calcified
8. Severe aortic regurgitation (>3+)
9. Severe mitral regurgitation (>3+) or ≥ moderate mitral stenosis
10. Pre-existing mechanical or bioprosthetic valve in any position
11. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of randomization
12. Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy, or hypercoagulable states
13. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of randomization
14. Hypertrophic cardiomyopathy with obstruction
15. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
16. Inability to tolerate or condition precluding treatment with anti-thrombotic therapy
17. Stroke or transient ischemic attack within 90 days of randomization
18. Renal insufficiency and/or renal replacement therapy
19. Active bacterial endocarditis within 180 days of randomization
20. Severe lung disease or currently on home oxygen
21. Severe pulmonary hypertension
22. History of cirrhosis or any active liver disease
23. Significant frailty as determined by the Heart Team
24. Significant abdominal or thoracic aortic disease that would preclude safe passage of the delivery system
25. Patient refuses blood products
26. BMI >50 kg/m2
27. Estimated life expectancy <24 months
28. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication
29. Currently participating in an investigational drug or another device study.
30. Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAVR; Transcatheter aortic valve replacement (TAVR)	Device: Edwards SAPIEN 3 / SAPIEN 3 Ultra THV; Patients will receive the SAPIEN 3 / SAPIEN 3 Ultra THV.; Other Names: SAPIEN 3, SAPIEN 3 Ultra
No Intervention: CS; Clinical surveillance (CS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death, all stroke, and unplanned cardiovascular hospitalization	The number of patients that have any of these conditions	When all patients have reached 2-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of 1) alive, 2) Kansas City Cardiomyopathy Questionnaire (KCCQ) score ≥75 and 3) KCCQ decrease ≤10 points	The number of patients that meet all of these criteria	2 years
Left Ventricular Health	Echocardiographic measurements that will assess the health of the left ventricle	2 years
Change in Left Ventricular Ejection Fraction (LVEF)	The average change in LVEF from baseline	2 years
New onset atrial fibrillation	The number of patients that develop this condition	When all patients have reached 2-year follow-up
Death or disabling stroke	The number of patients that have any of these conditions	When all patients have reached 2-year follow-up

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: Philippe Généreux, MD, Gagnon Cardiovascular Institute - Morristown Medical Center, Cardiovascular Research Foundation

Publications and helpful links

General Publications

• Zelis JM, Tonino PAL, Pijls NHJ, De Bruyne B, Kirkeeide RL, Gould KL, Johnson NP. Coronary Microcirculation in Aortic Stenosis: Pathophysiology, Invasive Assessment, and Future Directions. J Interv Cardiol. 2020 Jul 22;2020:4603169. doi: 10.1155/2020/4603169. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2017
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2032

Study Registration Dates

• First Submitted: January 30, 2017
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (Estimated): February 3, 2017

Study Record Updates

• Last Update Posted (Estimated): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Aortic valve; Asymptomatic; Transcatheter aortic valve replacement
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Heart Diseases; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: 2016-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes