Clinical trial NCT02701283: Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients
Official title: Transcatheter Aortic Valve Replacement With the Medtronic Transcatheter Aortic Valve Replacement System In Patients at Low Risk for Surgical Aortic Valve Replacement
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Valve Stenosis
Lead sponsor: Medtronic Cardiovascular
Sponsor class: INDUSTRY
First posted: 2016-03-08
Enrollment: 2223
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

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. 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.

Primary outcomes:
measure: 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
timeFrame: Randomized Controlled Trial - 24 months Continued Access Study - 12 months
Secondary outcomes:
measure: 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
timeFrame: 30 days
measure: New Pacemaker Implantation at 30 Days
timeFrame: 30 days
measure: Prosthetic Valve Endocarditis at 1 Year
timeFrame: 1 year
measure: Prosthetic Valve Thrombosis at 1 Year
timeFrame: 1 year
measure: All Stroke (Disabling and Non-disabling) at 1 Year
timeFrame: 1 year
measure: Life-threatening Bleeding at 1 Year
timeFrame: 1 year
measure: Valve-related Dysfunction Requiring Repeat Procedure at 1 Year
timeFrame: 1 year
measure: Valve-related Dysfunction (Moderate or Severe Stenosis or Regurgitation) at 1 Year, Randomized Controlled Trial
timeFrame: 1 year
measure: 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
timeFrame: Randomized Controlled Trial - 30 days and 1 year Continued Access Study - 1 year
measure: Repeat Hospitalization for Aortic Valve Disease at 1 Year, Randomized Controlled Trial
timeFrame: 1 year
Other outcomes:
measure: Hemodynamic Performance Metrics by Doppler Echocardiography: Percent of Participants With Degrees of Total Prosthetic Valve Regurgitation at 1 Year, Randomized Controlled Trial
timeFrame: 1 year
measure: Hemodynamic Performance Metrics by Doppler Echocardiography at 1 Year, Randomized Controlled Trial Effective Orifice Area (EOA) at 1 Year
timeFrame: 1 year
measure: Health-related Quality of Life as Assessed by European QoL (EQ-5D) at 1 Year, Randomized Controlled Trial
timeFrame: 1 year
measure: New York Heart Association (NYHA) Functional Classification at 1 Year, Randomized Controlled Trial
timeFrame: 1 year
measure: Hemodynamic Performance Metrics by Doppler Echocardiography at 1 Year, Randomized Controlled Trial Mean Aortic Gradient at 1 Year
timeFrame: 1 year
measure: Efficacy: Device Success Rate
timeFrame: Hospital discharge or 7 days post-procedure (whichever occurs first)
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: Los Angeles
country: United States
facility: University of Southern California University Hospital
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: Thousand Oaks
country: United States
facility: Los Robles Hospital & Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
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: Delray Beach
country: United States
facility: Delray Medical Center
state: Florida
city: Fort Myers
country: United States
facility: HealthPark Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute, Inc.
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Saint Vincent Heart Center of Indiana
state: Indiana
city: Des Moines
country: United States
facility: Mercy Medical Center
state: Iowa
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Louisville
country: United States
facility: Jewish Hospital
state: Kentucky
city: Houma
country: United States
facility: Terrebonne General Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: MedStar Union Memorial Hospital
state: Maryland
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
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: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Springfield
country: United States
facility: Mercy Hospital
state: Missouri
city: East Hills
country: United States
facility: Saint Francis Hospital
state: New York
city: Liverpool
country: United States
facility: Saint Joseph's Hospital Health Center
state: New York
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Fargo
country: United States
facility: Sanford Medical Center
state: North Dakota
city: Cincinnati
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Riverside Methodist Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health Science University
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geinsinger Medical Center
state: Pennsylvania
city: Harrisburg
country: United States
facility: Pinnacle Health
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center UPMC Presbyterian
state: Pennsylvania
city: Villanova
country: United States
facility: Paramount Heart
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Jack and Jane Hamilton Heart and Vascular Hospital
state: Texas
city: Houston
country: United States
facility: Baylor Saint Luke's Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University Hospital Salt Lake City Utah
state: Utah
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
city: Richmond
country: United States
facility: Saint Mary's Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
city: Darlinghurst
country: Australia
facility: Saint Vincent's Hospital Sydney
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital (FSH)
state: Western Australia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Health Hospital
state: Ontario
city: Montréal
country: Canada
facility: Glen Royal Victoria (McGill)
state: Quebec
city: Montréal
country: Canada
facility: Montreal Heart
city: Quebec
country: Canada
facility: IUCPQ
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
city: Lille
country: France
facility: Centre Hospitalier Régional Universitaire de Lille
city: Massy
country: France
facility: L'Hôpital Privé Jacques Cartier Massy
city: Toulouse
country: France
facility: Clinique Pasteur
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fokuoka
city: Sapporo
country: Japan
facility: Sapporo Higashi Tokushukai Hospital
state: Hokkaido
city: Tokyo
country: Japan
facility: Teikyo University Hospital
state: Itabashi-Ku
city: Kamakura
country: Japan
facility: Shonan Kamakura General Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Sendai Kousei Hospital
state: Miyagi
city: Suita
country: Japan
facility: National Cerebral and Cardiovasclular Center
state: Osaka
city: Suita
country: Japan
facility: The University of Osaka Hospital
state: Osaka
city: Fuchu
country: Japan
facility: Sakakibara Heart Institute
state: Tokyo
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital Nieuwegein
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Hamilton
country: New Zealand
facility: Waikato Hospital
Study officials:
affiliation: The Methodist Hospital Research Institute
name: Michael Reardon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale New Haven Hospital
name: John K. Forrest, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.