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SMART: SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial

Sponsor
Medtronic Cardiovascular (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04722250
Collaborator
(none)
700
Enrollment
76
Locations
2
Arms
81
Anticipated Duration (Months)
9.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Device: Medtronic Evolut PRO or Evolut PRO+ TAV Systems
  • Device: Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems
 N/A

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+ 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

  • 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
700 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial
Actual Study Start Date :
Apr 2, 2021
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Jan 1, 2028

Arms and Interventions

Arm Intervention/Treatment
Experimental: Medtronic Self-Expanding TAV

Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV.

Device: Medtronic Evolut PRO or Evolut PRO+ TAV Systems
TAVR treatment with Medtronic Evolut PRO or PRO+ System
Experimental: Edwards Balloon-Expandable THV

Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV.

Device: Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems
TAVR treatment with Edwards SAPIEN 3 or SAPIEN 3 Ultra System

Outcome Measures

Primary Outcome Measures

  1. Mortality, disabling stroke or heart failure rehospitalization [12 months]

    Percentage of participants with all-cause mortality, disabling stroke, or heart failure rehospitalization.

  2. Bioprosthetic Valve Dysfunction (BVD) [12 months]

    Percentage of participants with BVD (hemodynamic structural valve dysfunction, non-structural valve dysfunction, thrombosis, endocarditis, or aortic valve re-intervention) at 12 months.

Secondary Outcome Measures

  1. Percentage of participants with BVD in female subjects [12 months]

  2. Percentage of participants with Hemodynamic Structural Valve Dysfunction (HSVD) [12 months]

  3. Aortic valve mean gradient as a continuous variable [12 months]

  4. Effective Orifice Area (EOA) as a continuous variable [12 months]

  5. Rate of moderate or severe prothesis-patient mismatch (PPM) [30 days]

Other Outcome Measures

  1. Device success [30 days]

  2. Incidence of an early safety composite [30 days]

    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)

  3. Hospital readmission rate for any cause [30 days]

  4. Incidence of clinical efficacy [12 months and annually through 5 years]

    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)

  5. Percentage of participants with individual clinical endpoint components including mortality, disabling stroke and heart failure rehospitalization [12 months and annually to 5 years]

  6. New pacemaker implantation rate [30 days, 12 months and annually to 5 years]

  7. Aortic valve re-intervention rate [30 days, 12 months and annually to 5 years]

  8. 6-minute walk test (6MWT) change from baseline [30 days, 12 months and annually to 5 years]

  9. Quality of Life (QoL) change from baseline (Kansas City Cardiomyopathy Questionnaire [KCCQ] [30 days, 12 months and annually to 5 years]

    QoL: KCCQ

  10. Quality of Life (QoL) change from baseline EuroQol- 5 Dimension [EQ-5D]) [30 days, 12 months and annually to 5 years]

    QoL: EQ-5D

  11. BVD [2 to 5 years annually]

    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

  12. Echocardiographic measurements [Discharge, 30 days, 12 months and annually to 5 years]

    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)).

  13. Mean gradient ≥ 20 mmHg based on stress echocardiogram [12 months]

    Mean gradient ≥ 20 mmHg based on stress echocardiogram at select sites.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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+ 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+ 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Sutter Health San Francisco California United States 94109
2 Los Robles Hospital and Medical Center Thousand Oaks California United States 91360
3 University of Colorado Aurora Colorado United States 80045
4 Yale New Haven Hospital New Haven Connecticut United States 06510
5 WHC Washington MedStar Washington District of Columbia United States 20010
6 Morton Plant Hospital Clearwater Florida United States 33756
7 HealthPark Medical Center Fort Myers Florida United States 33908
8 University of Floriday Gainesville Florida United States 32608
9 Mount Sinai Medical Center Miami Beach Florida United States 33140
10 Emory Structural Heart Clinic and Emory University Midtown Atlanta Georgia United States 30308
11 Piedmont Atlanta Hospital Atlanta Georgia United States 30309
12 Wellstar Kennestone Hospital Marietta Georgia United States 30060
13 Advocate Christ Medical Center Oak Lawn Illinois United States 60453
14 University of Kansas Medical Center Kansas City Kansas United States 66160
15 AscensionVia Christi St. Francis Hospital Wichita Kansas United States 67226
16 Tufts Medical Center Boston Massachusetts United States 02111
17 University of Michigan Ann Arbor Michigan United States 48109
18 Ascension St. John Hospital Detroit Michigan United States 48236
19 Spectrum Health Grand Rapids Michigan United States 49503
20 St. Cloud Hospital Saint Cloud Minnesota United States 56303
21 Morristown Medical Center Morristown New Jersey United States 07960
22 Buffalo General Medical Center Buffalo New York United States 14203
23 NYU Langone Medical Center New York New York United States 10016
24 The Icahn School of Medicine at Mount Sinai New York New York United States 10029
25 Weill Cornell Medical Center New York New York United States 10065
26 Mission Hospital Asheville North Carolina United States 28801
27 TriHealth / Bethesda North Hospital Cincinnati Ohio United States 45220
28 University Hospitals Cleveland Medical Center Cleveland Ohio United States 44106
29 Cleveland Clinic Foundation Cleveland Ohio United States 44195
30 Hillcrest Medical Center Tulsa Oklahoma United States 74104
31 UPMC Pinnacle Harrisburg Harrisburg Pennsylvania United States 17110
32 Hospital of the University of Pennsylvania Philadelphia Pennsylvania United States 19104
33 Penn Presbyterian Medical Center Philadelphia Pennsylvania United States 19104
34 Allegheny General Hospital Pittsburgh Pennsylvania United States 15212
35 UPMC Presbyterian Pittsburgh Pennsylvania United States 15213
36 Lankenau Medical Center Wynnewood Pennsylvania United States 19096
37 York Hospital York Pennsylvania United States 17403
38 TriStar Centennial Medical Center Nashville Tennessee United States 37203
39 Seton Heart Institute Austin Texas United States 78705
40 Baylor Jack and Jane Hamilton Heart and Vascular Hospital Dallas Texas United States 75226
41 Texas Health Presbyterian Hospital/Dallas Dallas Texas United States 76231
42 Baylor Saint Luke's Hospital Houston Texas United States 77030
43 Houston Methodist Hospital Houston Texas United States 77030
44 University of Texas Health Sciences Center at Houston - Center for Advanced Heart Failure Houston Texas United States 77030
45 The Heart Hospital Baylor Plano Plano Texas United States 75093
46 Saint George Regional Hospital Saint George Utah United States 84770
47 Inova Fairfax Hospital Falls Church Virginia United States 22042
48 Sentara Norfolk General Hospital Norfolk Virginia United States 23507
49 J.W. Ruby Memorial Hospital/West Virginia University Morgantown West Virginia United States 26506
50 Providence Health-St. Paul's Hospital Vancouver British Columbia Canada V6Z 1Y6
51 Victoria Heart Institute Foundation/Royal Jubilee Hospital Victoria British Columbia Canada
52 Toronto General Hospital Toronto Ontario Canada M5G 2C4
53 St. Michaels Hospital/Unity Health Toronto Toronto Ontario Canada
54 Montreal Heart Institute Montréal Quebec Canada H1T 1C8
55 Rigshospitalet Copenhagen Denmark
56 Helsinki University Hospital Helsinki Finland
57 Centre Hospitalier Universitaire de Clermont-Ferrand Clermont-Ferrand France
58 CHU Bordeaux Pessac France
59 Clinique Pasteur Toulouse France
60 Hers-und Diabeteszentrum NRW - Ruhr -Universitati Bochum Bad Oeynhausen Germany
61 Deutsches Herzzentrum Berlin Berlin Germany
62 Kath. St.-Johannes-Gesellschaft Dortmund gGmbH - St. Johannes-Hospital Dortmund Dortmund Germany
63 Universitätsklinikum Düsseldorf Düsseldorf Germany
64 Universitätsklinikum Schleswig-Holstein - Campus Kiel Kiel Germany
65 Herzzentrum Leipzig GmbH Leipzig Germany
66 Deutsches Herzzentrum Munchen München Germany
67 Sheba Medical Center Ramat Gan Israel
68 Tel Aviv Sourasky Medical Center Tel Aviv Israel
69 Azienda Ospedaliero-Universitaria Pisana - Stabilimento di Cisanello Pisa Italy
70 AOU Integrata Verona Verona Italy
71 HagaZiekenhuis - Locatie Leyweg Den Haag Netherlands
72 Catharina Ziekenhuis Eindhoven Netherlands
73 Maastricht Universitair Medisch Centrum (MUMC) Maastricht Netherlands
74 Hospital Vall d'Hebron Barcelona Spain
75 Inselspital - Universitätsspital Bern Bern Switzerland
76 Royal Infirmary of Edinburgh Edinburgh United Kingdom

Sponsors and Collaborators

  • Medtronic Cardiovascular

Investigators

  • Principal Investigator: Howard Herrmann, MD, University of Pennsylvania, United States
  • Principal Investigator: Roxana Mehran, MD, Mount Sinai School of Medicine, United States
  • Principal Investigator: Didier Tchétché, MD, Clinique Pasteur Toulouse, France

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Medtronic Cardiovascular
ClinicalTrials.gov Identifier:
NCT04722250
Other Study ID Numbers:
  • MDT20023EVR012
First Posted:
Jan 25, 2021
Last Update Posted:
Jul 22, 2022
Last Verified:
Jul 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
Yes
Product Manufactured in and Exported from the U.S.:
Yes
Additional relevant MeSH terms:
Aortic Valve Stenosis
Constriction, Pathologic

Study Results

No Results Posted as of Jul 22, 2022