The Medtronic TAVR 2.0 US Clinical Study

Study Overview
=================
Brief Summary
-----------------
The study objective is to evaluate safety and efficacy of the Medtronic TAVR (Transcatheter Aortic Valve Replacement) 2.0 system in patients with severe symptomatic aortic stenosis who are considered at high through extreme risk for surgical aortic valve replacement

Detailed Description
-----------------
Prospective, single arm, multi-site study. Patients will be seen at pre and post procedure, discharge, 30 days, 6 months, 1 year, and annually up to 5 years.

Official Title
-----------------
The Medtronic TAVR 2.0 US Clinical Study

Conditions
-----------------
Aortic Valve Stenosis

Intervention / Treatment
-----------------
* Device: Medtronic Transcatheter Aortic Valve 2.0 Replacement System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Severe aortic stenosis, defined as aortic valve area of <1.0 cm2 (or aortic valve area index of <0.6 cm2/m2) by the continuity equation, AND mean gradient >40 mmHg OR maximal aortic valve velocity >4.0 m/sec by resting echocardiogram Society of Thoracic Surgeons(STS) score of ≥8 OR documented heart team agreement of ≥ high risk for aortic valve replacement due to frailty or co-morbidities Symptoms of aortic stenosis AND New York Heart Association (NYHA) Functional Class II or greater The subject and the treating physician agree that the subject will return for all required post procedure follow-up visits. Exclusion Criteria: Any condition considered a contraindication for placement of a bioprosthetic valve (eg, subject is indicated for mechanical prosthetic valve) A known hypersensitivity or contraindication to any of the following which cannot be adequately pre medicated: aspirin or heparin (HIT/HITTS) and bivalirudin ticlopidine and clopidogrel nitinol (titanium or nickel) contrast media Blood dyscrasias as defined: leukopenia (WBC <1000 mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states Untreated clinically significant coronary artery disease requiring revascularization Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) <20% by echocardiography, contrast ventriculography, or radionuclide ventriculography End stage renal disease requiring chronic dialysis or creatinine clearance <20 cc/min. Ongoing sepsis, including active endocarditis Any percutaneous coronary or peripheral interventional procedure with a bare metal or drug eluting stent performed within 30 days prior to study procedure Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 10 weeks of Heart Team assessment Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support Recent (within 6 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA) Gastrointestinal (GI) bleeding that would preclude anticoagulation Subject refuses a blood transfusion 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) Estimated life expectancy of less than 12 months due to associated non-cardiac co-morbid conditions 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 Currently participating in an investigational drug or another device study (excluding registries) Evidence of an acute myocardial infarction ≤30 days before the study procedure Need for emergency surgery for any reason Liver failure (Child-Pugh class C) Subject is pregnant or breast feeding Pre existing prosthetic heart valve in any position Mixed aortic valve disease (aortic stenosis with severe aortic regurgitation) Severe mitral regurgitation Severe tricuspid regurgitation Moderate or severe mitral stenosis Hypertrophic obstructive cardiomyopathy Echocardiographic or Multi-Slice Computed Tomography (MSCT) evidence of intracardiac mass, thrombus, or vegetation Congenital bicuspid or unicuspid valve verified by echocardiography Access vessel diameter <5.5 mm or <6.0 mm for patent left internal mammary artery (LIMA)
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medtronic Transcatheter Aortic Valve 2.0 Replacement System<br>Treatment of Aortic Stenosis by replacing native valve with the Medtronic Transcatheter Aortic Valve 2.0 System | Device: Medtronic Transcatheter Aortic Valve 2.0 Replacement System<br>* Treatment of severe symptomatic aortic stenosis in subjects who are considered at high through extreme risk for surgical aortic valve replacement.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality Rate |  | 30 days | 
| Stroke (Disabling) Rate |  | 30 days | 
| The Percentage of Subjects With None or Trace Prosthetic Regurgitation on Echocardiogram |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Rate of the VARC II Combined Safety Endpoint at 30 Days, Which Includes the Following Components: | All-cause mortality > All stroke (disabling and non-disabling) > Life-threatening bleeding > Acute kidney injury: stage 2 or 3 (including renal replacement therapy) > Coronary artery obstruction requiring intervention > Major vascular complication > Valve-related dysfunction requiring repeat procedure (BAV, TAVR, or SAVR) | 30 days | 
| Percentage of Participants With Life Threatening or Disabling Bleeding | Percentage of participants with life threatening or disabling bleeding - VARC-II definitions | 30 days | 
| Percentage of Participants With Major Vascular Complication | Percentage of participants with major vascular complication - VARC-II definition | 30 days | 
| Percentage of Participants With Coronary Artery Obstruction | Percentage of participants with coronary artery obstruction - VARC-II definitions | 30 days | 
| Percentage of Patient With Acute Kidney Injury- Stage 2 or 3 | Percentage of participants with Acute kidney injury - Stage 2 or 3 - VARC-II definitions | 30 days | 
| Percentage of Participants With Valve-related Dysfunction Requiring Repeat Procedure | Percentage of participants with valve-related dysfunction requiring repeat procedure - VARC-II definition | 30 days | 
| Device Success Rate (VARC II) |  | 24 hours to 7 days | 
| Hemodynamic Performance - Aortic Valve Area | Aortic Valve Area (cm2) by transthoracic echocardiogram | 30 days | 
| Hemodynamic Performance - Mean Gradient | Mean gradient (mmHg) by transthoracic echocardiogram | 30 days | 
| Hemodynamic Performance - Total Prosthetic Regurgitation Graded as None/Trace | Total prosthetic regurgitation by transthoracic echocardiogram | 30 days |