Medtronic CoreValve Evolut R U.S. Clinical Study (Evolut 34R Addendum)

Study Overview
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Brief Summary
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The study objectives are to assess the safety and efficacy of the CoreValve Evolut 34R transcatheter aortic valve replacement (TAVR) system in patients with severe symptomatic aortic stenosis who are considered at high or extreme risk for surgical aortic valve replacement.

Detailed Description
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This objective will be accomplished by a prospective, single arm, historical controlled, multi-site study involving up to 60 implanted subjects at up to 15 study sites in the United States. Procedural and 30 day safety and efficacy results from this study will be compared to appropriate historical control data for the Medtronic CoreValve System. Subjects will be followed up to 5 years following implantation.

Official Title
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Medtronic CoreValve Evolut R United States Clinical Study (Evolut 34R Addendum)

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: CoreValve Evolut 34R TAVR system


Participation Criteria
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Eligibility Criteria
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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. Subjects with low-flow/low gradient severe aortic stenosis can be included, provided low-dose dobutamine or exercise stress echocardiography demonstrates a mean gradient of > 40 mmHg or a maximal aortic valve velocity of > 4.0 m/sec, AND aortic valve area of < 1.0 cm2 (or aortic valve area index of < 0.6 cm2/m2). 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 (e.g. 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-ups 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. Anatomical exclusion criteria: 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. For transfemoral or transaxillary (subclavian) access: Access vessel diameter < 5.5 mm or <6.0 mm for patent left internal mammary artery (LIMA)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CoreValve Evolut 34R TAVR system<br>Treatment of Aortic Stenosis with Medtronic CoreValve Evolut R 34R TAVR System. | Device: CoreValve Evolut 34R TAVR system<br>* The CoreValve Evolut 34R System is a transcatheter aortic valve implantation system comprised of the following three components: Evolut 34R Transcatheter Aortic Valve (TAV) EnVeo R Delivery Catheter System (DCS) with EnVeo R InLine Sheath EnVeo R Loading System (LS)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With All-cause Mortality | Percentage of participants with all-cause mortality at 30 days | 30 Days | 
| Percentage of Participants With Stroke (Disabling) | Percentage of participants with disabling stroke (VARC-II definitions) at 30 days | 30 Days | 
| Device Success Rate | Device Success defined as: Absence of procedural mortality, AND Correct positioning of a single prosthetic heart valve into the proper anatomical location, AND Intended performance of the prosthetic heart valve, defined as the absence of patient prosthesis-mismatch and mean gradient < 20 mmHg (or peak velocity < 3 m/sec), AND Absence of moderate or severe prosthetic valve regurgitation | 24 hours to 7 days post implantation | 
| The Percentage of Subjects With no More Than Mild Prosthetic Regurgitation at Early Post Procedure Echocardiogram | The percentage of subjects with no more than mild prosthetic regurgitation at early post procedure echocardiogram as assessed by echo core laboratory | 24 hours to 7 days post implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With VARC II Combined Safety Endpoint Event at 30 Days | VARC II composite safety endpoint 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 post-implantation | 
| Percentage of Participants With Life Threatening or Disabling Bleeding | Percentage of participants with life threatening or disabling bleeding - see VARC-2 definitions for classification details | 30 days post-implantation | 
| Percentage of Participants With Major Vascular Complication | Percentage of participants with Major vascular complication - see VARC-2 definitions for additional details | 30 days | 
| Percentage of Participants With Acute Kidney Injury: Stage 2 or 3 | Percentage of participants with Acute Kidney Injury: Stage 2 or 3 - see VARC-2 definitions for additional details | 30 days | 
| Percentage of Participants With Coronary Artery Obstruction | Percentage of participants with coronary artery obstruction - see VARC-2 definitions for additional details | 30 days | 
| Percentage of Subjects With Valve-related Dysfunction Requiring Repeat Procedure | Percentage of subjects with valve-related dysfunction requiring repeat procedure - see VARC-2 definitions for additional details | 30 days | 
| Percentage of Subjects With Permanent Pacemaker Implant at 30 Days | Percentage of subjects with new permanent pacemaker implant at 30 days. | 30 days | 
| Percentage of Resheath and Recapture Success | Successful resheathing is defined as Evolut R TAV (including frame) was resheathed into the capsule of the delivery cathether to the desired amount intended, as verified by fluoroscopy. Successful recapture is defined as the entire Evolut R TAV (including frame) is resheathed into the capsule of the delivery catheter until there is no gap between the capsule and the tip, as verified by fluoroscopy. | Implant procedure | 
| Hemodynamic Performance Metrics - Mean Gradient | Mean gradient (mmHg) as measured by transthoracic echocardiogram and assessed by echo core laboratory | 30 days | 
| Hemodynamic Performance Metrics- Aortic Valve Area | Aortic valve area as measured by transthoracic echocardiogram and assessed by echo core laboratory | 30 Days | 
| Hemodynamic Performance Metrics - Total Prosthetic Regurgitation Graded as None/Trace | Total prosthetic regurgitation (none/trace) as measured by transthoracic echocardiogram and assessed by echo core laboratory | 30 days |