Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients

Aortic Valve Stenosis Clinical Trial

Official title:

Transcatheter Aortic Valve Replacement With the Medtronic Transcatheter Aortic Valve Replacement System In Patients at Low Risk for Surgical Aortic Valve Replacement

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02701283
• Other study ID #: 10234430Doc
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 2016
• Est. completion date: March 2026

Study information

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

Clinical Trial Summary

The study objective is to demonstrate that the safety and effectiveness of the Medtronic TAVR system as measured by rates of all-cause mortality or disabling stroke at two years is noninferior to SAVR in the treatment of severe aortic stenosis in subjects who have a low predicted risk of operative mortality for SAVR. The purpose of the expanded use addendum to the Medtronic TAVR in Low Risk Patients Trial protocol is to conclude the randomized phase of the trial and initiate the single-arm, non-randomized, continued access phase of the trial.

Description:

Multi-center, international, prospective, randomized, interventional, pre-market. Subjects will be randomized on 1:1 basis to either TAVR with the Medtronic TAVR system or to SAVR. Patients will be seen at pre and post-procedure, discharge, 30 days, 6 months, 1 year, 18 months, and annually through 10 years. The expanded use addendum is a multi-center, prospective, non-randomized continued access trial. All heart team approved subjects will be assigned to TAVR with the Medtronic TAVR system. Patients will be seen at pre and post-procedure, discharge, 30 days, and annually through 10 years. Enrollment is expected not to exceed 3660 attempted implants in the United States.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2223
• Est. completion date: March 2026
• Est. primary completion date: April 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A 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. Documented heart team agreement of 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. 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. 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

3. Blood dyscrasias as defined: leukopenia (WBC <1000 mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states.

4. Ongoing sepsis, including active endocarditis.

5. Any percutaneous coronary or peripheral interventional procedure with a bare metal stent within 30 days prior to randomization, or drug eluting stent performed within 180 days prior to randomization.

6. Multivessel coronary artery disease with a Syntax score >22 and/or unprotected left main coronary artery.

7. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 10 weeks of Heart Team assessment.

8. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.

9. Recent (within 2 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA).

10. Gastrointestinal (GI) bleeding that would preclude anticoagulation.

11. Subject refuses a blood transfusion.

12. Severe dementia (resulting in either inability to provide informed consent for the trial/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).

13. Estimated life expectancy of less than 24 months due to associated non-cardiac co-morbid conditions.

14. 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.

15. Currently participating in an investigational drug or another device trial (excluding registries).

16. Evidence of an acute myocardial infarction =30 days before the trial procedure due to unstable coronary artery disease (WHO criteria).

17. Need for emergency surgery for any reason.

18. Subject is pregnant or breast feeding.

19. Subject is less than legal age of consent, legally incompetent, or otherwise vulnerable

20. Pre-existing prosthetic heart valve in any position.

21. Severe mitral regurgitation amenable to surgical replacement or repair.

22. Severe tricuspid regurgitation amenable to surgical replacement or repair.

23. Moderate or severe mitral stenosis amenable to surgical replacement or repair.

24. Hypertrophic obstructive cardiomyopathy with left ventricular outflow gradient.

25. Bicuspid aortic valve verified by echocardiography, MDCT, or MRI.

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 aortopathy requiring ascending aortic replacement.

For transfemoral or transaxillary (subclavian) access:

30. 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 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

• Aortic Valve Stenosis

Intervention

Device:
• Medtronic Transcatheter Aortic Valve Replacement Systems
Treatment of severe aortic stenosis in subjects who have a low predicted risk of operative mortality for SAVR with Medtronic TAVR Systems
• Surgical Aortic Valve Replacement (SAVR)
Treatment of severe aortic stenosis in subjects who have a low predicted risk of operative mortality for SAVR with a commercially approved surgical bioprothesis

Locations

Country	Name	City	State
Australia	Monash Health	Clayton	Victoria
Australia	Saint Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital (FSH)	Murdoch	Western Australia
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Canada	London Health Sciences Centre	London	Ontario
Canada	Glen Royal Victoria (McGill)	Montréal	Quebec
Canada	Montreal Heart	Montréal
Canada	IUCPQ	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto
Canada	Toronto General Health Hospital	Toronto	Ontario
France	Centre Hospitalier Régional Universitaire de Lille	Lille
France	L'Hôpital Privé Jacques Cartier Massy	Massy
France	Clinique Pasteur	Toulouse
Japan	Sakakibara Heart Institute	Fuchu	Tokyo
Japan	Shonan Kamakura General Hospital	Kamakura	Kanagawa
Japan	Kokura Memorial Hospital	Kitakyushu	Fokuoka
Japan	Sapporo Higashi Tokushukai Hospital	Sapporo	Hokkaido
Japan	Sendai Kousei Hospital	Sendai	Miyagi
Japan	National Cerebral and Cardiovasclular Center	Suita	Osaka
Japan	Osaka University Hospital	Suita	Osaka
Japan	Teikyo University Hospital	Tokyo	Itabashi-Ku
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	St. Antonius Hospital Nieuwegein	Nieuwegein
Netherlands	Erasmus Medisch Centrum	Rotterdam
New Zealand	Waikato Hospital	Hamilton
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	MedStar Union Memorial Hospital	Baltimore	Maryland
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Vermont Medical Center	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Good Samaritan Hospital	Cincinnati	Ohio
United States	Morton Plant Hospital	Clearwater	Florida
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	OhioHealth Riverside Methodist Hospital	Columbus	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Baylor Jack and Jane Hamilton Heart and Vascular Hospital	Dallas	Texas
United States	Geinsinger Medical Center	Danville	Pennsylvania
United States	Delray Medical Center	Delray Beach	Florida
United States	Mercy Medical Center	Des Moines	Iowa
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Saint Francis Hospital	East Hills	New York
United States	Sanford Medical Center	Fargo	North Dakota
United States	HealthPark Medical Center	Fort Myers	Florida
United States	Spectrum Health Hospitals	Grand Rapids	Michigan
United States	Pinnacle Health	Harrisburg	Pennsylvania
United States	Terrebonne General Medical Center	Houma	Louisiana
United States	Baylor Saint Luke's Medical Center	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Saint Vincent Heart Center of Indiana	Indianapolis	Indiana
United States	The University of Kansas Hospital	Kansas City	Kansas
United States	Scripps Memorial Hospital La Jolla	La Jolla	California
United States	Saint Joseph's Hospital Health Center	Liverpool	New York
United States	University of Southern California University Hospital	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Northwell Health	Manhasset	New York
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Miami Hospital	Miami	Florida
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	El Camino Hospital	Mountain View	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	The Mount Sinai Hospital	New York	New York
United States	Integris Baptist Medical Center	Oklahoma City	Oklahoma
United States	Abrazo Arizona Heart Hospital	Phoenix	Arizona
United States	University of Pittsburgh Medical Center UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	Oregon Health Science University	Portland	Oregon
United States	Saint Mary's Hospital	Richmond	Virginia
United States	Strong Memorial Hospital	Rochester	New York
United States	Mercy General Hospital	Sacramento	California
United States	University Hospital Salt Lake City Utah	Salt Lake City	Utah
United States	Methodist Hospital San Antonio	San Antonio	Texas
United States	Swedish Medical Center	Seattle	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Mercy Hospital	Springfield	Missouri
United States	Tallahassee Research Institute, Inc.	Tallahassee	Florida
United States	Los Robles Hospital & Medical Center	Thousand Oaks	California
United States	Paramount Heart	Winchester	Virginia
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiovascular

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Japan,  Netherlands,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Total Prosthetic Valve Regurgitation at 1 Year, Randomized Controlled Trial	Reporting of prosthetic valve hemodynamic performance by degree of total prosthetic valve regurgitation	1 year
Other	Hemodynamic Performance Metrics by Doppler Echocardiography at 1 Year, Randomized Controlled Trial Effective Orifice Area (EOA) at 1 Year	Reporting of prosthetic valve hemodynamic performance by EOA	1 year
Other	Health-related Quality of Life as Assessed by European QoL (EQ-5D) at 1 Year, Randomized Controlled Trial	Quality of life 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	1 year
Other	New York Heart Association (NYHA) Functional Classification at 1 Year, Randomized Controlled Trial	Reporting of NYHA classification at 1 year; 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	1 year
Other	Hemodynamic Performance Metrics by Doppler Echocardiography at 1 Year, Randomized Controlled Trial Mean Aortic Gradient at 1 Year	Reporting of prosthetic valve hemodynamic performance by transvalvular mean aortic gradient	1 year
Other	Efficacy: Device Success Rate	Assessment of procedural effectiveness by meeting all of the following device success criteria: 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)	Hospital discharge or 7 days post-procedure (whichever occurs first)
Primary	Safety: All Cause Mortality or Disabling Stroke Rate at 24 Months, Randomized Controlled Trial Safety: All Cause Mortality or All Stroke Rate at 12 Months, Continued Access Study	Assessment of procedural safety by: All-cause mortality: all deaths from any cause after valve intervention. This includes all cardiovascular and non-cardiovascular deaths.; Disabling stroke: a modified rankin score (mRS) of 2 or more at 90 days post-stroke and an increase of at least one mRS category from an individual's pre-stroke baseline.; All stroke: any stroke after valve intervention (ischemic, hemorrhagic, or undetermined stroke).	Randomized Controlled Trial - 24 months Continued Access Study - 12 months
Secondary	RCT: Composite of Death, Disabling Stroke, Life-threatening Bleed, Major Vascular Complication, or AKI (II or III) at 30 Days CAS: Composite of Death, All Stroke, Life-threatening Bleed, or Major Vascular Complication at 30 Days	Randomized Controlled Trial: Combined clinical efficacy after 30 days was defined as the composite of all-cause mortality, disabling stroke, life-threatening bleed, major vascular complication, or AKI (II or III); Continued Access Study: Combined clinical efficacy after 30 days was defined as the composite of all-cause mortality, all stroke, life-threatening bleed, or major vascular complication	30 days
Secondary	New Pacemaker Implantation at 30 Days	The rate of new permanent pacemaker implant at 30 days	30 days
Secondary	Prosthetic Valve Endocarditis at 1 Year	The rate of prosthetic valve endocarditis at 1 year	1 year
Secondary	Prosthetic Valve Thrombosis at 1 Year	The rate of prosthetic valve thrombosis at 1 year	1 year
Secondary	All Stroke (Disabling and Non-disabling) at 1 Year	The rate of all stroke (disabling and non-disabling) at 1 year	1 year
Secondary	Life-threatening Bleeding at 1 Year	The rate of life-threatening bleeding at 1 year	1 year
Secondary	Valve-related Dysfunction Requiring Repeat Procedure at 1 Year	The rate of valve-related dysfunction requiring repeat procedure at 1 year	1 year
Secondary	Valve-related Dysfunction (Moderate or Severe Stenosis or Regurgitation) at 1 Year, Randomized Controlled Trial	Stenosis (moderate or severe); Any of the following: Peak aortic velocity >4 m/s OR mean aortic gradient >40 mmHg, AND EOA <0.8 cm2; Peak aortic velocity >4 m/s OR mean aortic gradient >40 mmHg, AND EOA =0.8 cm2, and DVI <0.25; Peak aortic velocity =4 m/s and mean aortic gradient = 40 mmHg, AND EOA <0.8 cm2, and DVI <0.25; Regurgitation (moderate or severe); Any of the following: Moderate or Severe Total Regurgitation; Moderate or Severe Paravalvular Regurgitation; Moderate or Severe Transvalvular Regurgitation	1 year
Secondary	Randomized Controlled Trial - Health-related Quality of Life as Assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30 Days and 1 Year Continued Access Study - Health-related Quality of Life as Assessed by KCCQ at 1 Year	Quality of life summary scores and change 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.	Randomized Controlled Trial - 30 days and 1 year Continued Access Study - 1 year
Secondary	Repeat Hospitalization for Aortic Valve Disease at 1 Year, Randomized Controlled Trial	The rate of repeat hospitalization for aortic valve disease at 1 year	1 year