Clinical trial NCT04722250: SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial
Official title: SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Symptomatic Aortic Stenosis
Aortic Valve Stenosis
Aortic Valve Replacement
Lead sponsor: Medtronic Cardiovascular
Sponsor class: INDUSTRY
First posted: 2021-01-25
Enrollment: 1103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to generate clinical evidence on valve safety and performance of self-expanding (SE) versus balloon-expandable (BE) transcatheter aortic valve replacement (TAVR) in subjects with a small aortic annulus and symptomatic severe native aortic stenosis.

Additionally, a stress echocardiography sub-study will be conducted as part of the SMART Trial at select sites. The purpose of the sub-study is to evaluate performance of SE versus BE TAVR in subjects with a small aortic annulus and symptomatic severe native aortic stenosis after undergoing exercise stress echocardiographic testing.

Detailed description: This is a prospective, multi-center, international, randomized controlled, post-market trial.

The primary objectives of the trial are to demonstrate clinical non-inferiority and hemodynamic superiority of the Evolut PRO/PRO+/FX System when compared to subjects treated with the SAPIEN 3/3 Ultra System at 12 months post-procedure.

Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE Transcatheter Aortic Valve (TAV) or an Edwards BE Transcatheter Heart Valve (THV). Data will be collected at pre- and post-procedure, at discharge, at 30 days, and once a year until the 5-year follow-up is completed.

Product Names:

* Medtronic Evolut PRO and Evolut PRO+ TAV Systems, Evolut FX System (Commercially available in the United States and may be used upon commercial availability in Canada.)
* Edwards SAPIEN 3 and SAPIEN 3 Ultra THV Systems

The exercise stress echocardiographic testing at select SMART Trial sites seeks to evaluate the performance of the prosthetic aortic valve during exercise. The stress echocardiogram assessment will be conducted as part of the 12-month visit for participating subjects.

Eligibility criteria: Inclusion Criteria:

* Heart Team agrees that the subject is deemed symptomatic and is a candidate for transcatheter aortic valve replacement (TAVR)
* Subject has a predicted risk of operative mortality \< 15% as determined by the local Heart Team
* Subject has severe aortic stenosis as determined by transthoracic echocardiography (TTE) at rest
* Subject has a small aortic annulus as determined by Multi-detector computed tomography (MDCT)
* Subject's anatomy is appropriate for both Medtronic Evolut PRO/PRO+/FX TAV and Edwards SAPIEN 3/3 Ultra TAV
* Subject's anatomy is suitable for TAVR via transfemoral vessel access
* Subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits

Exclusion Criteria:

* Estimated life expectancy of fewer than 2 years
* Multivessel coronary artery disease with a Syntax score \>32 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).
* Participating in another trial that may influence the outcome of this trial
* Need for an emergent procedure for any reason
* Contraindicated for treatment with the Evolut PRO/PRO+/FX and Edwards SAPIEN 3/3 Ultra TAV in accordance with the Instructions for Use
* 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
* Pregnant, nursing, or planning to be pregnant
* Subject is less than the legal age of consent, legally incompetent, unable to provide his/her own informed consent, or otherwise vulnerable
* Subject has an active COVID-19 infection or relevant history of COVID-19
* Previous aortic valve replacement

Primary outcomes:
measure: Mortality, Disabling Stroke or Heart Failure Rehospitalization
timeFrame: 12 months
measure: Bioprosthetic Valve Dysfunction (BVD)
timeFrame: 12 months
Secondary outcomes:
measure: Percentage of Participants With BVD in Female Subjects
timeFrame: 12 months
measure: Percentage of Participants With Hemodynamic Structural Valve Dysfunction (HSVD)
timeFrame: 12 months
measure: Hemodynamic Mean Gradient as Continuous Variable
timeFrame: 12 months
measure: Effective Orifice Area (EOA) as a Continuous Variable
timeFrame: 12 months
measure: Rate of Moderate or Severe Prothesis-patient Mismatch (PPM)
timeFrame: 30 days
Other outcomes:
measure: Device Success
timeFrame: 30 days
measure: Incidence of an Early Safety Composite
timeFrame: 30 days
measure: Hospital Readmission Rate for Any Cause
timeFrame: 30 days
measure: Incidence of Clinical Efficacy
timeFrame: 12 months
measure: Percentage of Participants With Individual Clinical Endpoint Components Including Mortality, Disabling Stroke and Heart Failure Rehospitalization
timeFrame: 12 months
measure: New Pacemaker Implantation Rate
timeFrame: 30 days, 12 months
measure: Aortic Valve Re-intervention Rate
timeFrame: 30 days, 12 months
measure: 6-minute Walk Test (6MWT) Change From Baseline
timeFrame: 30 days
measure: 6-minute Walk Test (6MWT) Change From Baseline
timeFrame: 12 Months
measure: Quality of Life (QoL) Change From Baseline (Kansas City Cardiomyopathy Questionnaire [KCCQ]
timeFrame: 30 days
measure: Quality of Life (QoL) Change From Baseline (Kansas City Cardiomyopathy Questionnaire [KCCQ])
timeFrame: 12 Months
measure: Quality of Life (QoL) Change From Baseline (EuroQol- 5 Dimension [EQ-5D])
timeFrame: 30 days
measure: Quality of Life (QoL) Change From Baseline (EuroQol- 5 Dimension [EQ-5D])
timeFrame: 12 Months
measure: Mean Gradient ≥ 20 mmHg Based on Stress Echocardiogram
timeFrame: 12 months
Locations:
city: La Jolla
country: United States
facility: Scripps Memorial Hospital
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: Sutter Health
state: California
city: Thousand Oaks
country: United States
facility: Los Robles Hospital and Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: WHC Washington MedStar
state: District of Columbia
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Fort Myers
country: United States
facility: HealthPark Medical Center
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Atlanta
country: United States
facility: Emory Structural Heart Clinic and Emory University Midtown
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Marietta
country: United States
facility: Wellstar Kennestone Hospital
state: Georgia
city: Evanston
country: United States
facility: NorthShore Health Systems
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Carmel
country: United States
facility: Saint Vincent Heart Center of Indiana
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: AscensionVia Christi St. Francis Hospital
state: Kansas
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Ascension St. John Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Cloud
country: United States
facility: St. Cloud Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Buffalo General Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: The Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Memorial Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: TriHealth / Bethesda North Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Tulsa
country: United States
facility: Hillcrest Medical Center
state: Oklahoma
city: Harrisburg
country: United States
facility: UPMC Pinnacle Harrisburg
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
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: TriStar Centennial Medical Center
state: Tennessee
city: Nashville
country: United States
facility: St. Thomas West Hospital
state: Tennessee
city: Austin
country: United States
facility: Seton Heart Institute
state: Texas
city: Dallas
country: United States
facility: Baylor Jack and Jane Hamilton Heart and Vascular Hospital
state: Texas
city: Dallas
country: United States
facility: Texas Health Presbyterian Hospital/Dallas
state: Texas
city: Houston
country: United States
facility: Baylor Saint Luke's Hospital
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: University of Texas Health Sciences Center at Houston - Center for Advanced Heart Failure
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Saint George
country: United States
facility: Saint George Regional Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Morgantown
country: United States
facility: J.W. Ruby Memorial Hospital/West Virginia University
state: West Virginia
city: Vancouver
country: Canada
facility: Providence Health-St. Paul's Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Victoria Heart Institute Foundation/Royal Jubilee Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michaels Hospital/Unity Health Toronto
state: Ontario
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire de Clermont-Ferrand
city: Pessac
country: France
facility: CHU Bordeaux
city: Toulouse
country: France
facility: Clinique Pasteur
city: Bad Oeynhausen
country: Germany
facility: Hers-und Diabeteszentrum NRW - Ruhr -Universitati Bochum
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Dortmund
country: Germany
facility: Kath. St.-Johannes-Gesellschaft Dortmund gGmbH - St. Johannes-Hospital Dortmund
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Campus Kiel
city: Leipzig
country: Germany
facility: Helios Health Institute GmbH
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Campus Lübeck
city: München
country: Germany
facility: Deutsches Herzzentrum Munchen
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: Policlinico Sant' Orsala - Malpighi
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana - Stabilimento di Cisanello
city: Verona
country: Italy
facility: AOU Integrata Verona
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis - Locatie Leyweg
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum (MUMC)
city: Carnaxide
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental, E.P.E. Hospital de Santa Cruz
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Bern
country: Switzerland
facility: Inselspital - Universitätsspital Bern
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals NHS Trust - Leeds General Infirmary
Study officials:
affiliation: University of Pennsylvania, United States
name: Howard Herrmann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mount Sinai School of Medicine, United States
name: Roxana Mehran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinique Pasteur Toulouse, France
name: Didier Tchétché, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Herrmann HC, Abdel-Wahab M, Attizzani GF, Batchelor W, Bleiziffer S, Verdoliva S, Chang Y, Gada H, Gillam L, Guerrero M, Mahoney PD, Petronio AS, Rogers T, Rovin J, Szerlip M, Whisenant B, Mehran R, Tchetche D. Rationale and design of the SMall Annuli Randomized To Evolut or SAPIEN Trial (SMART Trial). Am Heart J. 2022 Jan;243:92-102. doi: 10.1016/j.ahj.2021.09.011. Epub 2021 Sep 26.