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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02701283




Registration number
NCT02701283
Ethics application status
Date submitted
26/02/2016
Date registered
8/03/2016
Date last updated
1/08/2024

Titles & IDs
Public title
Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients
Scientific title
Transcatheter Aortic Valve Replacement With the Medtronic Transcatheter Aortic Valve Replacement System In Patients at Low Risk for Surgical Aortic Valve Replacement
Secondary ID [1] 0 0
10234430Doc
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aortic Valve Stenosis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Medtronic Transcatheter Aortic Valve Replacement Systems
Treatment: Devices - Surgical Aortic Valve Replacement (SAVR)

Experimental: Medtronic Transcatheter Aortic Valve Replacement Systems - Treatment of Aortic Stenosis with the Medtronic CoreValve System Transcatheter Aortic Valve Implantation (TAVI) device or the Medtronic Corevalve Evolut R System Transcatheter Aortic Valve Implantation (TAVI)

Active comparator: Surgical Aortic Valve Replacement (SAVR) - Treatment of Aortic Stenosis with commercial Surgical Aortic Valve Replacement (SAVR)


Treatment: Devices: 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

Treatment: Devices: 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
Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Randomized Controlled Trial - 24 months Continued Access Study - 12 months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
30 days
Secondary outcome [2] 0 0
New Pacemaker Implantation at 30 Days
Timepoint [2] 0 0
30 days
Secondary outcome [3] 0 0
Prosthetic Valve Endocarditis at 1 Year
Timepoint [3] 0 0
1 year
Secondary outcome [4] 0 0
Prosthetic Valve Thrombosis at 1 Year
Timepoint [4] 0 0
1 year
Secondary outcome [5] 0 0
All Stroke (Disabling and Non-disabling) at 1 Year
Timepoint [5] 0 0
1 year
Secondary outcome [6] 0 0
Life-threatening Bleeding at 1 Year
Timepoint [6] 0 0
1 year
Secondary outcome [7] 0 0
Valve-related Dysfunction Requiring Repeat Procedure at 1 Year
Timepoint [7] 0 0
1 year
Secondary outcome [8] 0 0
Valve-related Dysfunction (Moderate or Severe Stenosis or Regurgitation) at 1 Year, Randomized Controlled Trial
Timepoint [8] 0 0
1 year
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Randomized Controlled Trial - 30 days and 1 year Continued Access Study - 1 year
Secondary outcome [10] 0 0
Repeat Hospitalization for Aortic Valve Disease at 1 Year, Randomized Controlled Trial
Timepoint [10] 0 0
1 year

Eligibility
Key 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.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
NA
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2026
Actual
Sample size
Target
Accrual to date
Final
2223
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Saint Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Fiona Stanley Hospital (FSH) - Murdoch
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Maryland
Country [14] 0 0
United States of America
State/province [14] 0 0
Massachusetts
Country [15] 0 0
United States of America
State/province [15] 0 0
Michigan
Country [16] 0 0
United States of America
State/province [16] 0 0
Minnesota
Country [17] 0 0
United States of America
State/province [17] 0 0
Missouri
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
North Dakota
Country [21] 0 0
United States of America
State/province [21] 0 0
Ohio
Country [22] 0 0
United States of America
State/province [22] 0 0
Oklahoma
Country [23] 0 0
United States of America
State/province [23] 0 0
Oregon
Country [24] 0 0
United States of America
State/province [24] 0 0
Pennsylvania
Country [25] 0 0
United States of America
State/province [25] 0 0
South Carolina
Country [26] 0 0
United States of America
State/province [26] 0 0
Tennessee
Country [27] 0 0
United States of America
State/province [27] 0 0
Texas
Country [28] 0 0
United States of America
State/province [28] 0 0
Utah
Country [29] 0 0
United States of America
State/province [29] 0 0
Vermont
Country [30] 0 0
United States of America
State/province [30] 0 0
Virginia
Country [31] 0 0
United States of America
State/province [31] 0 0
Washington
Country [32] 0 0
United States of America
State/province [32] 0 0
Wisconsin
Country [33] 0 0
Canada
State/province [33] 0 0
Ontario
Country [34] 0 0
Canada
State/province [34] 0 0
Quebec
Country [35] 0 0
Canada
State/province [35] 0 0
Montréal
Country [36] 0 0
Canada
State/province [36] 0 0
Toronto
Country [37] 0 0
France
State/province [37] 0 0
Lille
Country [38] 0 0
France
State/province [38] 0 0
Massy
Country [39] 0 0
France
State/province [39] 0 0
Toulouse
Country [40] 0 0
Japan
State/province [40] 0 0
Fokuoka
Country [41] 0 0
Japan
State/province [41] 0 0
Hokkaido
Country [42] 0 0
Japan
State/province [42] 0 0
Itabashi-Ku
Country [43] 0 0
Japan
State/province [43] 0 0
Kanagawa
Country [44] 0 0
Japan
State/province [44] 0 0
Miyagi
Country [45] 0 0
Japan
State/province [45] 0 0
Osaka
Country [46] 0 0
Japan
State/province [46] 0 0
Tokyo
Country [47] 0 0
Netherlands
State/province [47] 0 0
Eindhoven
Country [48] 0 0
Netherlands
State/province [48] 0 0
Nieuwegein
Country [49] 0 0
Netherlands
State/province [49] 0 0
Rotterdam
Country [50] 0 0
New Zealand
State/province [50] 0 0
Hamilton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Medtronic Cardiovascular
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT02701283
Trial related presentations / publications
Ramlawi B, Deeb GM, Yakubov SJ, Markowitz AH, Hughes GC, Kiaii RB, Huang J, Kleiman NS, Reardon MJ. Mechanisms of Death in Low-Risk Patients After Transcatheter or Surgical Aortic Valve Replacement. Cardiovasc Revasc Med. 2022 Sep;42:1-5. doi: 10.1016/j.carrev.2022.03.027. Epub 2022 Mar 29.
Forrest JK, Deeb GM, Yakubov SJ, Rovin JD, Mumtaz M, Gada H, O'Hair D, Bajwa T, Sorajja P, Heiser JC, Merhi W, Mangi A, Spriggs DJ, Kleiman NS, Chetcuti SJ, Teirstein PS, Zorn GL 3rd, Tadros P, Tchetche D, Resar JR, Walton A, Gleason TG, Ramlawi B, Iskander A, Caputo R, Oh JK, Huang J, Reardon MJ. 2-Year Outcomes After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients. J Am Coll Cardiol. 2022 Mar 8;79(9):882-896. doi: 10.1016/j.jacc.2021.11.062.
Lanz J, Reardon MJ, Pilgrim T, Stortecky S, Deeb GM, Chetcuti S, Yakubov SJ, Gleason TG, Huang J, Windecker S. Incidence and Outcomes of Infective Endocarditis After Transcatheter or Surgical Aortic Valve Replacement. J Am Heart Assoc. 2021 Oct 5;10(19):e020368. doi: 10.1161/JAHA.120.020368. Epub 2021 Sep 28.
Blanke P, Leipsic JA, Popma JJ, Yakubov SJ, Deeb GM, Gada H, Mumtaz M, Ramlawi B, Kleiman NS, Sorajja P, Askew J, Meduri CU, Kauten J, Melnitchouk S, Inglessis I, Huang J, Boulware M, Reardon MJ; Evolut Low Risk LTI Substudy Investigators. Bioprosthetic Aortic Valve Leaflet Thickening in the Evolut Low Risk Sub-Study. J Am Coll Cardiol. 2020 May 19;75(19):2430-2442. doi: 10.1016/j.jacc.2020.03.022. Epub 2020 Mar 28.
Popma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, O'Hair D, Bajwa T, Heiser JC, Merhi W, Kleiman NS, Askew J, Sorajja P, Rovin J, Chetcuti SJ, Adams DH, Teirstein PS, Zorn GL 3rd, Forrest JK, Tchetche D, Resar J, Walton A, Piazza N, Ramlawi B, Robinson N, Petrossian G, Gleason TG, Oh JK, Boulware MJ, Qiao H, Mugglin AS, Reardon MJ; Evolut Low Risk Trial Investigators. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med. 2019 May 2;380(18):1706-1715. doi: 10.1056/NEJMoa1816885. Epub 2019 Mar 16.
Leipsic J, Bax JJ, Webb JG, Martin R, Blanke P. Trials Testing the Value of Imaging Use in Valve Disease and in Transcatheter Valvular Interventions. JACC Cardiovasc Imaging. 2017 Mar;10(3):286-295. doi: 10.1016/j.jcmg.2016.09.031.
Public notes

Contacts
Principal investigator
Name 0 0
Michael Reardon, MD
Address 0 0
The Methodist Hospital Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02701283