Clinical trial NCT03635424: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Bicuspid Aortic Valve
Lead sponsor: Medtronic Cardiovascular
Sponsor class: INDUSTRY
First posted: 2018-08-17
Enrollment: 150
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Safety: Percent of Participants With All-Cause Mortality or Disabling Stroke Rate at 30 Days Post-procedure.
timeFrame: 30 days
measure: Efficacy: Percent of Participants Who Meet All Device Success Criteria at 30 Days Post-procedure.
timeFrame: 7 days
Secondary outcomes:
measure: All-Cause Mortality Rate
timeFrame: 1 year and annually through 10 years
measure: All Stroke (Disabling and Non-Disabling) Rate
timeFrame: 1 year and annually through 10 years
measure: Percent of Participants With New Permanent Pacemaker Implantation at 30 Days Post-procedure.
timeFrame: 30 days
measure: Percent of Participants Who Experience a Myocardial Infarction at 30 Days Post-procedure.
timeFrame: 30 days
measure: Percent of Participants With a Life-Threatening Bleeding Event at 30 Days Post-procedure.
timeFrame: 30 days
measure: Percent of Participants With Prosthetic Valve Endocarditis at 30 Days Post-procedure.
timeFrame: 30 days
measure: Percent of Participant With Prosthetic Valve Thrombosis at 30 Days Post-procedure.
timeFrame: 30 days
measure: Percent pf Participants With Valve-Related Dysfunction Requiring Repeat Procedure at 30 Days Post-procedure.
timeFrame: 30 days
measure: Percent of Participants With a Repeat Hospitalization for Aortic Valve Disease at 30 Days Post-procedure.
timeFrame: 30 days
measure: Percent of Participants With a Repeat Hospitalization for Ascending Aorta Disease at 30 Days Post-procedure.
timeFrame: 30 days
measure: Hemodynamic Performance Metrics by Doppler Echocardiography: Mean Aortic Gradient Reported as Mean Average at Baseline and 30 Days
timeFrame: 30 days
measure: Hemodynamic Performance Metrics by Doppler Echocardiography: Effective Orifice Area Reported as Mean Average at Baseline and 30 Days.
timeFrame: 30 days
measure: Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Total Prosthetic Valve Regurgitation at Baseline and 30 Days
timeFrame: 30 days
measure: Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Paravalvular Prosthetic Regurgitation at 30 Days
timeFrame: 30 days
measure: Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Transvalvular Prosthetic Regurgitation at 30 Days
timeFrame: 30 days
measure: New York Heart Association (NYHA) Functional Classification at Baseline and 30 Days
timeFrame: 30 days
measure: Change in Health-related Quality of Life (QoL) as Assessed by Kansas City Cardiomyopathy (KCCQ) Instrument at Baseline and 30 Days
timeFrame: 30 days
measure: Health-related Quality of Life (QoL) as Assessed by European QoL (EQ-5D) at Baseline and 30 Days.
timeFrame: 30 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Abrazo Arizona Heart Hospital
state: Arizona
city: La Jolla
country: United States
facility: Scripps Memorial Hospital La Jolla
state: California
city: Thousand Oaks
country: United States
facility: Los Robles Hospital & Medical Center
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Fort Myers
country: United States
facility: HealthPark Medical Center
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: Roslyn
country: United States
facility: Saint Francis Hospital
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Riverside Methodist Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University Hospital
state: Oregon
city: Harrisburg
country: United States
facility: UPMC Pinnacle Harrisburg Campus
state: Pennsylvania
city: Villanova
country: United States
facility: Paramount Heart
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Jack and Jane Hamilton Heart & Vascular Hospital
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: The Methodist Hospital Research Institute
name: Michael Reardon, MD
role: STUDY_CHAIR
affiliation: Yale University
name: John Forrest, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Paramount Heart
name: Basel Ramlawi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.