SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial

Aortic Valve Stenosis Clinical Trial

— SMART  

Official title:

SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04722250
• Other study ID #: MDT20023EVR012
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 2, 2021
• Est. completion date: December 2027

Study information

• Verified date: April 2024
• Source: Medtronic Cardiovascular
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 716
• Est. completion date: December 2027
• Est. primary completion date: November 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Valve Replacement
• Aortic Valve Stenosis
• Constriction, Pathologic
• Symptomatic Aortic Stenosis

Intervention

Device:
• Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems
TAVR treatment with Medtronic Evolut PRO, PRO+ System or Evolut FX System (where commercially available)
• Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems
TAVR treatment with Edwards SAPIEN 3 or SAPIEN 3 Ultra System

Locations

Country	Name	City	State
Canada	Montreal Heart Institute	Montréal	Quebec
Canada	St. Michaels Hospital/Unity Health Toronto	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Providence Health-St. Paul's Hospital	Vancouver	British Columbia
Canada	Victoria Heart Institute Foundation/Royal Jubilee Hospital	Victoria	British Columbia
Denmark	Rigshospitalet	Copenhagen
Finland	Helsinki University Hospital	Helsinki
France	Centre Hospitalier Universitaire de Clermont-Ferrand	Clermont-Ferrand
France	CHU Bordeaux	Pessac
France	Clinique Pasteur	Toulouse
Germany	Hers-und Diabeteszentrum NRW - Ruhr -Universitati Bochum	Bad Oeynhausen
Germany	Deutsches Herzzentrum Berlin	Berlin
Germany	Kath. St.-Johannes-Gesellschaft Dortmund gGmbH - St. Johannes-Hospital Dortmund	Dortmund
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Universitätsklinikum Schleswig-Holstein - Campus Kiel	Kiel
Germany	Helios Health Institute GmbH	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein - Campus Lübeck	Lübeck
Germany	Deutsches Herzzentrum Munchen	München
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Policlinico Sant' Orsala - Malpighi	Bologna
Italy	Azienda Ospedaliero-Universitaria Pisana - Stabilimento di Cisanello	Pisa
Italy	AOU Integrata Verona	Verona
Netherlands	HagaZiekenhuis - Locatie Leyweg	Den Haag
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Maastricht Universitair Medisch Centrum (MUMC)	Maastricht
Portugal	Centro Hospitalar de Lisboa Ocidental, E.P.E. Hospital de Santa Cruz	Carnaxide
Spain	Hospital Vall d'Hebron	Barcelona
Switzerland	Inselspital - Universitätsspital Bern	Bern
United Kingdom	Royal Infirmary of Edinburgh	Edinburgh
United Kingdom	The Leeds Teaching Hospitals NHS Trust - Leeds General Infirmary	Leeds
United States	University of Michigan	Ann Arbor	Michigan
United States	Mission Hospital	Asheville	North Carolina
United States	Emory Structural Heart Clinic and Emory University Midtown	Atlanta	Georgia
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Seton Heart Institute	Austin	Texas
United States	Tufts Medical Center	Boston	Massachusetts
United States	Buffalo General Medical Center	Buffalo	New York
United States	Saint Vincent Heart Center of Indiana	Carmel	Indiana
United States	UNC Memorial Hospital	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	TriHealth / Bethesda North Hospital	Cincinnati	Ohio
United States	Morton Plant Hospital	Clearwater	Florida
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Baylor Jack and Jane Hamilton Heart and Vascular Hospital	Dallas	Texas
United States	Texas Health Presbyterian Hospital/Dallas	Dallas	Texas
United States	Ascension St. John Hospital	Detroit	Michigan
United States	NorthShore Health Systems	Evanston	Illinois
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	HealthPark Medical Center	Fort Myers	Florida
United States	University of Florida	Gainesville	Florida
United States	Spectrum Health	Grand Rapids	Michigan
United States	UPMC Pinnacle Harrisburg	Harrisburg	Pennsylvania
United States	Baylor Saint Luke's Hospital	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Texas Health Sciences Center at Houston - Center for Advanced Heart Failure	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Scripps Memorial Hospital	La Jolla	California
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Wellstar Kennestone Hospital	Marietta	Georgia
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	J.W. Ruby Memorial Hospital/West Virginia University	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Intermountain Medical Center	Murray	Utah
United States	St. Thomas West Hospital	Nashville	Tennessee
United States	TriStar Centennial Medical Center	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	NYU Langone Medical Center	New York	New York
United States	The Icahn School of Medicine at Mount Sinai	New York	New York
United States	Weill Cornell Medical Center	New York	New York
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	The Heart Hospital Baylor Plano	Plano	Texas
United States	Mayo Clinic	Rochester	Minnesota
United States	St. Cloud Hospital	Saint Cloud	Minnesota
United States	Saint George Regional Hospital	Saint George	Utah
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Sutter Health	San Francisco	California
United States	Los Robles Hospital and Medical Center	Thousand Oaks	California
United States	Hillcrest Medical Center	Tulsa	Oklahoma
United States	WHC Washington MedStar	Washington	District of Columbia
United States	AscensionVia Christi St. Francis Hospital	Wichita	Kansas
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	York Hospital	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiovascular

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Finland,  France,  Germany,  Israel,  Italy,  Netherlands,  Portugal,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Device success		30 days
Other	Incidence of an early safety composite	Incidence of an early safety composite at 30 days defined as: All-cause mortality; All stroke (disabling and non-disabling); Life-threatening bleeding; Acute kidney injury-Stage 2 or 3 (including renal replacement therapy); Coronary artery obstruction requiring intervention; Major vascular complication; Valve-related dysfunction requiring repeat procedure (BAV, TAVR, or SAVR)	30 days
Other	Hospital readmission rate for any cause		30 days
Other	Incidence of clinical efficacy	Incidence of clinical efficacy (after 30 days) at 12 months and annually to 5 years defined as a composite of: All-cause mortality; All stroke (disabling and non-disabling); Requiring hospitalizations for valve-related symptoms or worsening congestive heart failure; NYHA class III or IV; Valve-related dysfunction (mean aortic valve gradient =20 mmHg, EOA =0.9-1.1 cm2 and/or Doppler velocity index (DVI) <0. 35m/s, AND/OR moderate or severe prosthetic valve regurgitation)	12 months and annually through 5 years
Other	Percentage of participants with individual clinical endpoint components including mortality, disabling stroke and heart failure rehospitalization		12 months and annually to 5 years
Other	New pacemaker implantation rate		30 days, 12 months and annually to 5 years
Other	Aortic valve re-intervention rate		30 days, 12 months and annually to 5 years
Other	6-minute walk test (6MWT) change from baseline		30 days, 12 months and annually to 5 years
Other	Quality of Life (QoL) change from baseline (Kansas City Cardiomyopathy Questionnaire [KCCQ]	QoL: KCCQ	30 days, 12 months and annually to 5 years
Other	Quality of Life (QoL) change from baseline EuroQol- 5 Dimension [EQ-5D])	QoL: EQ-5D	30 days, 12 months and annually to 5 years
Other	BVD	BVD at 2 to 5 years annually post-procedure including any of the following: Hemodynamic structural valve dysfunction (HSVD); Non-structural valve dysfunction (NSVD); Thrombosis; Endocarditis; Aortic valve re-intervention	2 to 5 years annually
Other	Echocardiographic measurements	Echocardiographic measurements (i.e. EOA, mean gradient, peri-valvular leak (PVL), left ventricular mass regression, and DVI (severe <0.25, moderate 0.25-0.5, mild >0.5)).	Discharge, 30 days, 12 months and annually to 5 years
Other	Mean gradient = 20 mmHg based on stress echocardiogram	Mean gradient = 20 mmHg based on stress echocardiogram at select sites.	12 months
Primary	Mortality, disabling stroke or heart failure rehospitalization	Percentage of participants with all-cause mortality, disabling stroke, or heart failure rehospitalization.	12 months
Primary	Bioprosthetic Valve Dysfunction (BVD)	Percentage of participants with BVD (hemodynamic structural valve dysfunction, non-structural valve dysfunction, thrombosis, endocarditis, or aortic valve re-intervention) at 12 months.	12 months
Secondary	Percentage of participants with BVD in female subjects		12 months
Secondary	Percentage of participants with Hemodynamic Structural Valve Dysfunction (HSVD)		12 months
Secondary	Aortic valve mean gradient as a continuous variable		12 months
Secondary	Effective Orifice Area (EOA) as a continuous variable		12 months
Secondary	Rate of moderate or severe prothesis-patient mismatch (PPM)		30 days