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

• ClinicalTrials.gov Identifier: NCT03635424
• Recruitment Status: Active, not recruiting
• First Posted: August 17, 2018
• Results First Posted: December 21, 2020
• Last Update Posted: May 2, 2024
• Sponsor: Medtronic Cardiovascular
• Information provided by (Responsible Party): Medtronic Cardiovascular

Tracking Information

• First Submitted Date: July 31, 2018
• First Posted Date: August 17, 2018
• Results First Submitted Date: October 29, 2020
• Results First Posted Date: December 21, 2020
• Last Update Posted Date: May 2, 2024
• Actual Study Start Date: October 30, 2018
• Actual Primary Completion Date: November 13, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 24, 2020)

• Safety: Percent of Participants With All-Cause Mortality or Disabling Stroke Rate at 30 Days Post-procedure. [ Time Frame: 30 days ]
  Rate of of all-cause mortality or disabling stroke rate at 30 days
• Efficacy: Percent of Participants Who Meet All Device Success Criteria at 30 Days Post-procedure. [ Time Frame: 7 days ]
  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)

Original Primary Outcome Measures (submitted: August 13, 2018)

• Device and procedure safety: All-cause mortality or disabling stroke rate [ Time Frame: 30 days ]
  All-cause mortality or disabling stroke rate
• Device and Procedure Efficacy: Device success rate [ Time Frame: 7 days ]
  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)

Current Secondary Outcome Measures (submitted: November 24, 2020)

• All-Cause Mortality Rate [ Time Frame: 1 year and annually through 10 years ]
  Rate of all cause mortality
• All Stroke (Disabling and Non-Disabling) Rate [ Time Frame: 1 year and annually through 10 years ]
  Rate of disabling and non-disabling strokes
• Percent of Participants With New Permanent Pacemaker Implantation at 30 Days Post-procedure. [ Time Frame: 30 days ]
  Rate of new permanent pacemaker implantation at 30 days post-procedure (excludes patients with pre-existing pacemaker at baseline)
• Percent of Participants Who Experience a Myocardial Infarction at 30 Days Post-procedure. [ Time Frame: 30 days ]
  The rate of myocardial infarction at 30 days
• Percent of Participants With a Life-Threatening Bleeding Event at 30 Days Post-procedure. [ Time Frame: 30 days ]
  Rate of life-threatening (or disabling) bleeding at 30 days
• Percent of Participants With Prosthetic Valve Endocarditis at 30 Days Post-procedure. [ Time Frame: 30 days ]
  Rate of prosthetic valve endocarditis at 30 days
• Percent of Participant With Prosthetic Valve Thrombosis at 30 Days Post-procedure. [ Time Frame: 30 days ]
  Rate of prosthetic valve thrombosis at 30 days
• Percent pf Participants With Valve-Related Dysfunction Requiring Repeat Procedure at 30 Days Post-procedure. [ Time Frame: 30 days ]
  Rate of valve-related dysfunction requiring repeat procedure at 30 days
• Percent of Participants With a Repeat Hospitalization for Aortic Valve Disease at 30 Days Post-procedure. [ Time Frame: 30 days ]
  Rate of repeat hospitalization for aortic valve disease at 30 days
• Percent of Participants With a Repeat Hospitalization for Ascending Aorta Disease at 30 Days Post-procedure. [ Time Frame: 30 days ]
  Rate of repeat hospitalization for ascending aorta disease at 30 days
• Hemodynamic Performance Metrics by Doppler Echocardiography: Mean Aortic Gradient Reported as Mean Average at Baseline and 30 Days [ Time Frame: 30 days ]
  Reporting of prosthetic valve hemodynamic performance by transvalvular mean aortic gradient
• Hemodynamic Performance Metrics by Doppler Echocardiography: Effective Orifice Area Reported as Mean Average at Baseline and 30 Days. [ Time Frame: 30 days ]
  Change in hemodynamic performance metrics by Doppler echocardiography measured by effective orifice area.
• Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Total Prosthetic Valve Regurgitation at Baseline and 30 Days [ Time Frame: 30 days ]
  Reporting of prosthetic valve hemodynamic performance by degree of total prosthetic valve regurgitation at 30 days post-procedure
• Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Paravalvular Prosthetic Regurgitation at 30 Days [ Time Frame: 30 days ]
  Reporting of prosthetic valve hemodynamic performance by degree of paravalvular regurgitation at 30 days post-procedure
• Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Transvalvular Prosthetic Regurgitation at 30 Days [ Time Frame: 30 days ]
  Reporting of prosthetic valve hemodynamic performance by degree of transvalvular regurgitation at 30 days post-procedure
• New York Heart Association (NYHA) Functional Classification at Baseline and 30 Days [ Time Frame: 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.
• Change in Health-related Quality of Life (QoL) as Assessed by Kansas City Cardiomyopathy (KCCQ) Instrument at Baseline and 30 Days [ Time Frame: 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.
• Health-related Quality of Life (QoL) as Assessed by European QoL (EQ-5D) at Baseline and 30 Days. [ Time Frame: 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

Original Secondary Outcome Measures (submitted: August 13, 2018)

• All-cause mortality rate [ Time Frame: 1 year and annually through 10 years ]
  Rate of all cause mortality
• All stroke (disabling and non-disabling) rate [ Time Frame: 1 year and annually through 10 years ]
  Rate of disabling and non-disabling strokes
• New permanent pacemaker implantation rate [ Time Frame: 30 days ]
  Rate of new permanent pacemaker implantation
• Life-threatening bleeding rate [ Time Frame: 30 days, one year, and annually though 10 years ]
  Rate of life-threatening bleeding
• Prosthetic valve endocarditis rate [ Time Frame: 30 days, one year, and annually though 10 years ]
  Rate of prosthetic valve endocarditis
• Prosthetic valve thrombosis rate [ Time Frame: 30 days, one year, and annually though 10 years ]
  Rate of prosthetic valve thrombosis
• Valve-related dysfunction requiring repeat procedure rate [ Time Frame: 30 days, one year, and annually though 10 years ]
  Rate of valve-related dysfunction requiring repeat procedure
• Repeat hospitalization for aortic valve disease rate [ Time Frame: 30 days, one year, and annually though 10 years ]
  Rate of repeat hospitalization for aortic valve disease
• Repeat hospitalization for ascending aorta disease rate [ Time Frame: 30 days, one year, and annually though 10 years ]
  Rate of repeat hospitalization for ascending aorta disease
• Change in hemodynamic performance (mean aortic valve gradient) by Doppler echocardiography [ Time Frame: Baseline, 30 days, one year, and annually though 5 years, and at years 7 and 10 ]
  Change in hemodynamic performance metrics by Doppler echocardiography measured by mean aortic valve gradient
• Change in Hemodynamic performance (effective orifice area) by Doppler echocardiography [ Time Frame: Baseline, 30 days, one year, and annually though 5 years, and at years 7 and 10 ]
  Change in hemodynamic performance metrics by Doppler echocardiography measured by effective orifice area.
• Change in Hemodynamic performance (degree of total, peri, and transvalvular prosthetic regurgitation) by Doppler echocardiography [ Time Frame: Baseline, 30 days, one year, and annually though 5 years, and at years 7 and 10 ]
  Change in hemodynamic performance metrics by Doppler echocardiography measured by degree of total, peri, and transvalvular prosthetic regurgitation.
• Change in New York Heart Association (NYHA) functional classification [ Time Frame: Baseline, 30 days, one year, and annually though 5 years, and at years 7 and 10 ]
  Change in NYHA functional classification
• Change in Health-related quality of life as assessed by Kansas City Cardiomyopathy (KCCQ) instrument [ Time Frame: Baseline, 30 days, one year, annually through 5 years ]
  Change in health-related quality of life assessed by Kansas City Cardiomyopathy
• Change in Health-related quality of life as assessed by EQ-5D survey [ Time Frame: Baseline, 30 days, and one year ]
  Change in health-related quality of life as assessed by EQ-5D survey

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Medtronic Transcatheter Aortic Valve Replacement (TAVR) Low Risk Bicuspid Study
• Official Title: 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)
• Brief Summary: 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

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
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Bicuspid Aortic Valve

Intervention

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

Study Arms

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

Intervention: Device: Medtronic TAVR Systems

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 13, 2018): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2030
• Actual Primary Completion Date: November 13, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03635424
• Other Study ID Numbers: 10790330DOC
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Medtronic Cardiovascular
• Original Responsible Party: Same as current
• Current Study Sponsor: Medtronic Cardiovascular
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Medtronic Cardiovascular
• Verification Date: April 2024