Clinical trial NCT03042104: EARLY TAVR: Evaluation of TAVR Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis
Official title: Evaluation of Transcatheter Aortic Valve Replacement Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Diseases
Aortic Stenosis, Severe
Keywords: Aortic valve
Asymptomatic
Transcatheter aortic valve replacement
Lead sponsor: Edwards Lifesciences
Sponsor class: INDUSTRY
First posted: 2017-02-03
Enrollment: 901
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause death, all stroke, and unplanned cardiovascular hospitalization
timeFrame: When all patients have reached 2-year follow-up
Secondary outcomes:
measure: Composite of 1) alive, 2) Kansas City Cardiomyopathy Questionnaire (KCCQ) score ≥75 and 3) KCCQ decrease ≤10 points
timeFrame: 2 years
measure: Left Ventricular Health
timeFrame: 2 years
measure: Change in Left Ventricular Ejection Fraction (LVEF)
timeFrame: 2 years
measure: New onset atrial fibrillation
timeFrame: When all patients have reached 2-year follow-up
measure: Death or disabling stroke
timeFrame: When all patients have reached 2-year follow-up
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center
state: Arizona
city: Burlingame
country: United States
facility: Mills Peninsula Health Services
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Pasadena
country: United States
facility: Huntington Hospital
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: Kaiser San Francisco Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics Palo Alto
state: California
city: Loveland
country: United States
facility: UC Health Northern Colorado (Medical Center of the Rockies)
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center DC
state: District of Columbia
city: Gainesville
country: United States
facility: The Cardiac & Vascular Institute Research Foundation
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center Chicago
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem Research Institution
state: Illinois
city: Lisle
country: United States
facility: Alexian Brothers Hospital Network
state: Illinois
city: Springfield
country: United States
facility: Prairie Education and Research Cooperative
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: West Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Hyannis
country: United States
facility: Cape Cod Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Heart
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City Mid America
state: Missouri
city: Missoula
country: United States
facility: St. Patrick Hospital
state: Montana
city: Lebanon
country: United States
facility: Mary Hitchcock Memorial Hospital
state: New Hampshire
city: Morristown
country: United States
facility: Atlantic Health System Hospital Corp - Morristown Medical Center
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Piscataway
country: United States
facility: Rutgers Robert Wood Johnson Medical School
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: University at Buffalo - Kaleida Health
state: New York
city: Mineola
country: United States
facility: NYU Langone Hosptial - Long Island
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/ New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Cornell University
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolina's Health System
state: North Carolina
city: Raleigh
country: United States
facility: NC Heart and Vascular (Rex Hospital)
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital, Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel Health System
state: Ohio
city: Columbus
country: United States
facility: The Ohio Health Research Institute
state: Ohio
city: Clackamas
country: United States
facility: Kaiser Portland
state: Oregon
city: Harrisburg
country: United States
facility: Pinnacle Health
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny - Singer Research Institute
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: York
country: United States
facility: York Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Dallas
country: United States
facility: Texas Health Physician Group
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center Salt Lake City
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute (Fairfax Inova)
state: Virginia
city: Norfolk
country: United States
facility: Sentara Cardiovascular Research Institute
state: Virginia
city: Roanoke
country: United States
facility: Carilion Medical Center
state: Virginia
city: Everett
country: United States
facility: Providence Everett
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Spokane
country: United States
facility: Sacred Heart Medical Center
state: Washington
city: Charleston
country: United States
facility: CAMC Clinical Trials Center
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: Gagnon Cardiovascular Institute - Morristown Medical Center, Cardiovascular Research Foundation
name: Philippe Généreux, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.