Medtronic Transcatheter Aortic Valve Replacement (TAVR) Low Risk Bicuspid Study

Transcatheter Aortic Valve Replacement (TAVR) With Medtronic TAVR System in Patients With Severe Bicuspid Aortic Valve Stenosis and at Low Predicted Risk of Mortality With Surgical Aortic Valve Replacement (SAVR)

The objective of the trial is to evaluate the procedural safety and efficacy of the Medtronic TAVR system in patients with bicuspid aortic anatomy and severe aortic stenosis at low risk for SAVR

Study Overview

• Status: Active, not recruiting
• Conditions: Bicuspid Aortic Valve
• Intervention / Treatment: Device: Medtronic TAVR Systems

Detailed Description

Multi-center, prospective, single arm

All subjects will be treated with a Medtronic TAVR system. Subject follow-ups will be conducted at pre and post-procedure, discharge, 30 days, 1 year, and annually through 10 years

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Abrazo Arizona Heart Hospital
  • California
    • La Jolla, California, United States, 92037
      • Scripps Memorial Hospital La Jolla
    • Thousand Oaks, California, United States, 91360
      • Los Robles Hospital & Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • Florida
    • Clearwater, Florida, United States, 33756
      • Morton Plant Hospital
    • Fort Myers, Florida, United States, 33908
      • HealthPark Medical Center
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Abbott Northwestern Hospital
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital
    • Roslyn, New York, United States, 11576
      • Saint Francis Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43214
      • OhioHealth Riverside Methodist Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University Hospital
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17101
      • UPMC Pinnacle Harrisburg Campus
  • Texas
    • Dallas, Texas, United States, 75226
      • Baylor Jack and Jane Hamilton Heart & Vascular Hospital
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Virginia
    • Winchester, Virginia, United States, 22601
      • Paramount Heart
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Severe aortic stenosis, defined as follows:

   1. For symptomatic patients:

      Aortic valve area ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), OR mean gradient ≥40 mmHg, OR Maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest

   2. For asymptomatic patients:

   Very severe aortic stenosis with an aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND maximal aortic velocity ≥5.0 m/sec, or mean gradient ≥60 mmHg by transthoracic echocardiography at rest, OR

   Aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND a mean gradient ≥40 mmHg or maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest, AND an exercise tolerance test that demonstrates a limited exercise capacity, abnormal BP response, or arrhythmia OR

   Aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND mean gradient ≥40 mmHg, or maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest, AND a left ventricular ejection fraction <50%.

2. Patient is considered low risk for SAVR, where low risk is defined as predicted risk of mortality for SAVR <3% at 30 days per multidisciplinary local heart team assessment.
3. Bicuspid aortic valve anatomy (all sub-types) confirmed by MDCT.
4. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

Exclusion Criteria:

1. Any condition considered a contraindication for placement of a bioprosthetic valve (eg, subject is indicated for mechanical prosthetic valve).
2. Age less than 60 years

3. A known hypersensitivity or contraindication to any of the following that cannot be adequately pre-medicated:

   1. aspirin or heparin (HIT/HITTS) and bivalirudin
   2. ticlopidine and clopidogrel
   3. Nitinol (titanium or nickel)
   4. contrast media
4. Blood dyscrasias as defined: leukopenia (WBC <1000 mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
5. Ongoing sepsis, including active endocarditis.
6. Any percutaneous coronary or peripheral interventional procedure with a bare metal stent or drug eluting stent performed within 30 days prior to screening committee approval.
7. Multivessel coronary artery disease with a Syntax score >22 and/or unprotected left main coronary artery.
8. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 10 weeks of Heart Team assessment.
9. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
10. Recent (within 2 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
11. Gastrointestinal (GI) bleeding that would preclude anticoagulation.
12. Subject refuses a blood transfusion.
13. Severe dementia (resulting in either inability to provide informed consent for the study/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
14. Estimated life expectancy of less than 24 months due to associated non-cardiac co-morbid conditions.
15. 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.
16. Currently participating in an investigational drug or another device study (excluding registries).
17. Evidence of an acute myocardial infarction ≤30 days before the study procedure due to unstable coronary artery disease (WHO criteria).
18. Need for emergency surgery for any reason.
19. Subject is pregnant or breast feeding.

20. Subject is legally incompetent, or otherwise vulnerable

    Anatomical exclusion criteria:

21. Pre-existing prosthetic heart valve in any position.
22. Severe mitral regurgitation amenable to surgical replacement or repair.
23. Severe tricuspid regurgitation amenable to surgical replacement or repair.
24. Moderate or severe mitral stenosis amenable to surgical replacement or repair.
25. Hypertrophic obstructive cardiomyopathy with left ventricular outflow gradient.
26. Prohibitive left ventricular outflow tract calcification.
27. Sinus of Valsalva diameter unsuitable for placement of the self-expanding bioprosthesis
28. Aortic annulus diameter of <18 or >30 mm.
29. Significant ascending aortopathy requiring surgical repair

30. Ascending aorta diameter > 4.5 cm

    For transfemoral or transaxillary (subclavian) access:

31. Access vessel mean diameter <5.0 mm for Evolut 23R, 26R, or 29R mm TAV, or access vessel mean diameter <5.5 mm for Evolut 34R mm or Evolut PRO 23R, 26R, 29 R mm TAV. However, for transaxillary (subclavian) access in patients with a patent LIMA, access vessel mean diameter <5.5mm for Evolut 23R, 26R, or 29R mm TAV, or access vessel mean diameter <6.0 mm for the Evolut 34R or Evolut PRO TAV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medtronic TAVR Systems; Treatment of patients with bicuspid aortic anatomy and severe aortic stenosis at low risk for SAVR with Medtronic Evolut PRO and Evolut R systems	Device: Medtronic TAVR Systems; Treatment of patients with bicuspid aortic anatomy and severe aortic stenosis at low risk for SAVR with Medtronic Evolut PRO and Evolut R systems

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Percent of Participants With All-Cause Mortality or Disabling Stroke Rate at 30 Days Post-procedure.	Rate of of all-cause mortality or disabling stroke rate at 30 days	30 days
Efficacy: Percent of Participants Who Meet All Device Success Criteria at 30 Days Post-procedure.	Device success rate, defined as: Absence of procedural mortality, AND; Correct positioning of a single prosthetic heart valve into the proper anatomical location, AND; Absence of moderate or severe total prosthetic valve regurgitation (at 18 hours to 7 days)	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-Cause Mortality Rate	Rate of all cause mortality	1 year and annually through 10 years
All Stroke (Disabling and Non-Disabling) Rate	Rate of disabling and non-disabling strokes	1 year and annually through 10 years
Percent of Participants With New Permanent Pacemaker Implantation at 30 Days Post-procedure.	Rate of new permanent pacemaker implantation at 30 days post-procedure (excludes patients with pre-existing pacemaker at baseline)	30 days
Percent of Participants Who Experience a Myocardial Infarction at 30 Days Post-procedure.	The rate of myocardial infarction at 30 days	30 days
Percent of Participants With a Life-Threatening Bleeding Event at 30 Days Post-procedure.	Rate of life-threatening (or disabling) bleeding at 30 days	30 days
Percent of Participants With Prosthetic Valve Endocarditis at 30 Days Post-procedure.	Rate of prosthetic valve endocarditis at 30 days	30 days
Percent of Participant With Prosthetic Valve Thrombosis at 30 Days Post-procedure.	Rate of prosthetic valve thrombosis at 30 days	30 days
Percent pf Participants With Valve-Related Dysfunction Requiring Repeat Procedure at 30 Days Post-procedure.	Rate of valve-related dysfunction requiring repeat procedure at 30 days	30 days
Percent of Participants With a Repeat Hospitalization for Aortic Valve Disease at 30 Days Post-procedure.	Rate of repeat hospitalization for aortic valve disease at 30 days	30 days
Percent of Participants With a Repeat Hospitalization for Ascending Aorta Disease at 30 Days Post-procedure.	Rate of repeat hospitalization for ascending aorta disease at 30 days	30 days
Hemodynamic Performance Metrics by Doppler Echocardiography: Mean Aortic Gradient Reported as Mean Average at Baseline and 30 Days	Reporting of prosthetic valve hemodynamic performance by transvalvular mean aortic gradient	30 days
Hemodynamic Performance Metrics by Doppler Echocardiography: Effective Orifice Area Reported as Mean Average at Baseline and 30 Days.	Change in hemodynamic performance metrics by Doppler echocardiography measured by effective orifice area.	30 days
Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Total Prosthetic Valve Regurgitation at Baseline and 30 Days	Reporting of prosthetic valve hemodynamic performance by degree of total prosthetic valve regurgitation at 30 days post-procedure	30 days
Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Paravalvular Prosthetic Regurgitation at 30 Days	Reporting of prosthetic valve hemodynamic performance by degree of paravalvular regurgitation at 30 days post-procedure	30 days
Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Transvalvular Prosthetic Regurgitation at 30 Days	Reporting of prosthetic valve hemodynamic performance by degree of transvalvular regurgitation at 30 days post-procedure	30 days
New York Heart Association (NYHA) Functional Classification at Baseline and 30 Days	Reporting of NYHA classification change from baseline to 30 days NYHA Classification criteria: Class I: Subjects with cardiac disease but without resulting limitations of physical activity. Class I: Subjects with cardiac disease resulting in slight limitation of physical activity. Class III: Subjects with cardiac disease resulting in marked limitation of physical activity. Class IV: Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort.	30 days
Change in Health-related Quality of Life (QoL) as Assessed by Kansas City Cardiomyopathy (KCCQ) Instrument at Baseline and 30 Days	QoL overall summary (all domains below) and clinical summary (physical function and symptoms only) scores and change in summary scores from baseline using the following measures: • KCCQ: Quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	30 days
Health-related Quality of Life (QoL) as Assessed by European QoL (EQ-5D) at Baseline and 30 Days.	QoL summary scores and change from baseline using the following measures: • EQ-5D: Measures 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that can be converted to utilities using an algorithm. Utilities range from 0 to 1, with 1 representing perfect health, and 0 corresponding to the worst imaginable health state	30 days

Collaborators and Investigators

• Sponsor: Medtronic Cardiovascular
• Investigators: Study Chair: Michael Reardon, MD, The Methodist Hospital Research Institute; Principal Investigator: John Forrest, MD, Yale University; Principal Investigator: Basel Ramlawi, MD, Paramount Heart

Publications and helpful links

General Publications

• Forrest JK, Ramlawi B, Deeb GM, Zahr F, Song HK, Kleiman NS, Chetcuti SJ, Michelena HI, Mangi AA, Skiles JA, Huang J, Popma JJ, Reardon MJ. Transcatheter Aortic Valve Replacement in Low-risk Patients With Bicuspid Aortic Valve Stenosis. JAMA Cardiol. 2021 Jan 1;6(1):50-57. doi: 10.1001/jamacardio.2020.4738.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2018
• Primary Completion (Actual): November 13, 2019
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: July 31, 2018
• First Submitted That Met QC Criteria: August 13, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Aortic Valve Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Valve Diseases; Bicuspid Aortic Valve Disease
• Other Study ID Numbers: 10790330DOC

Drug and device information, study documents

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