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

Bicuspid Aortic Valve Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03635424
• Other study ID #: 10790330DOC
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 30, 2018
• Est. completion date: December 2030

Study information

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

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: December 2030
• Est. primary completion date: November 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bicuspid Aortic Valve
• Bicuspid Aortic Valve Disease
• Heart Valve Diseases

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

Locations

Country	Name	City	State
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Morton Plant Hospital	Clearwater	Florida
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	OhioHealth Riverside Methodist Hospital	Columbus	Ohio
United States	Baylor Jack and Jane Hamilton Heart & Vascular Hospital	Dallas	Texas
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	HealthPark Medical Center	Fort Myers	Florida
United States	Spectrum Health Hospital	Grand Rapids	Michigan
United States	UPMC Pinnacle Harrisburg Campus	Harrisburg	Pennsylvania
United States	Houston Methodist Hospital	Houston	Texas
United States	Scripps Memorial Hospital La Jolla	La Jolla	California
United States	North Shore University Hospital	Manhasset	New York
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	The Mount Sinai Hospital	New York	New York
United States	Abrazo Arizona Heart Hospital	Phoenix	Arizona
United States	Oregon Health & Science University Hospital	Portland	Oregon
United States	Saint Francis Hospital	Roslyn	New York
United States	Tallahassee Memorial Hospital	Tallahassee	Florida
United States	Los Robles Hospital & Medical Center	Thousand Oaks	California
United States	Paramount Heart	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiovascular

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	All-Cause Mortality Rate	Rate of all cause mortality	1 year and annually through 10 years
Secondary	All Stroke (Disabling and Non-Disabling) Rate	Rate of disabling and non-disabling strokes	1 year and annually through 10 years
Secondary	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
Secondary	Percent of Participants Who Experience a Myocardial Infarction at 30 Days Post-procedure.	The rate of myocardial infarction at 30 days	30 days
Secondary	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
Secondary	Percent of Participants With Prosthetic Valve Endocarditis at 30 Days Post-procedure.	Rate of prosthetic valve endocarditis at 30 days	30 days
Secondary	Percent of Participant With Prosthetic Valve Thrombosis at 30 Days Post-procedure.	Rate of prosthetic valve thrombosis at 30 days	30 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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