Cerebral Protection in Transcatheter Aortic Valve Replacement

Study Overview
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Brief Summary
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The Sentinel System will be a safe and effective method for capturing and removing embolic material (thrombus/debris) during transcatheter aortic valve replacement in order to reduce the ischemic burden in the cerebral anterior circulation.

Detailed Description
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The Sentinel™ Cerebral Protection System is indicated for use as an embolic capture and retrieval system intended to reduce the ischemic burden in the cerebral anterior circulation while performing transcatheter aortic valve replacement. The objective of this study is to assess the safety and efficacy of the Claret Medical Sentinel Cerebral Protection System used for embolic protection during Transcatheter Aortic Valve Replacement (TAVR) compared to TAVR standard of care (without embolic protection). The study population is comprised of subjects with severe symptomatic calcified native aortic valve stenosis who meet the commercially approved indications for TAVR with the Edwards SAPIEN THV or SAPIEN XT and comply with the inclusion/exclusion criteria.

Official Title
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Cerebral Protection in Transcatheter Aortic Valve Replacement - The SENTINEL Study

Conditions
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Severe Symptomatic Calcified Native Aortic Valve Stenosis

Intervention / Treatment
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* Device: Cerebral Protection System-The SENTINEL System with TAVR
* Device: TAVR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Approved indications for commercially available Edwards SAPIEN Transcatheter Heart Valve, model 9000TFX or SAPIEN XT, model 9300TFX meeting one of the three sub-criteria below: SAPIEN transfemoral delivery in subjects with severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency and with ejection fraction >20% who have been examined by a heart team including an experienced cardiac surgeon and a cardiologist and found to either be: inoperable and in whom existing co-morbidities would not preclude the expected benefit from correction of the aortic stenosis; or be operative candidates for aortic valve replacement but who have a Society of Thoracic Surgeons predicted operative risk score >8% or are judged by the heart team to be at a 15% risk of mortality for surgical aortic valve replacement. or transapical delivery in subjects with severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency and with ejection fraction > 20% who have been examined by a heart team including an experienced cardiac surgeon and a cardiologist and found to be operative candidates for aortic valve replacement but who have a Society of Thoracic Surgeons operative risk score 8% or are judged by the heart team to be at a 15% risk of mortality for surgical aortic valve replacement. SAPIEN XT (Transfemoral or Transapical only) in patients with symptomatic heart disease due to severe native calcific aortic stenosis (aortic valve area ≤ 1.0 cm2 or aortic valve area index ≤ 0.6 cm2/m2, a mean aortic valve gradient of ≥ 40 mmHg, or a peak aortic-jet velocity of ≥ 4.0 m/s), and with native anatomy appropriate for the 23, 26, or 29 mm valve system, who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score ≥8% or at a ≥15% risk of mortality at 30 days). Compatible left common carotid artery (6.5 - 10 mm) and brachiocephalic artery (9 - 15 mm) diameters without significant stenosis (> 70%) as determined by Multi-Slice Computed Tomography (MSCT) scan or equivalent imaging modality The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visit The subject or the subject's legal representative has been informed of the nature of the trial, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site Exclusion Criteria: General Vasculature in the right extremity precluding 6Fr sheath radial or brachial access Inadequate circulation to the right extremity as evidenced by signs of artery occlusion (modified Allen's test) or absence of radial/brachial pulse Hemodialysis shunt, graft, or arterio-venous fistula involving the upper extremity vasculature Evidence of an acute myocardial infarction ≤ 1 month before the intended treatment Aortic valve is a congenital unicuspid or bicuspid valve; or is non-calcified Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation >3+) Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (unless part of planned strategy for treatment of concomitant coronary artery disease) Pre-existing prosthetic heart valve in any position, prosthetic ring, or severe (greater than 3+) mitral insufficiency Blood dyscrasias as defined: Leukopenia, acute anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy Hemodynamic instability requiring inotropic support or mechanical heart assistance. Need for emergency surgery for any reason Hypertrophic cardiomyopathy with or without obstruction Severe ventricular dysfunction with LVEF ≤20% Echocardiographic evidence of intracardiac or aortic mass, thrombus, or vegetation Symptomatic or asymptomatic severe occlusive carotid disease requiring concomitant CEA/stenting Subject has undergone carotid stenting or carotid endarterectomy within the previous 6 weeks Active peptic ulcer or upper GI bleeding within the prior 3 months A known hypersensitivity or contraindication to aspirin, heparin, ticlopidine, or clopidogrel, or sensitivity to contrast media, which cannot be adequately pre-medicated Recent (within 6 months) CVA or a TIA Renal insufficiency (creatinine > 3.0 mg/dL or GFR < 30) and/or renal replacement therapy at the time of screening Life expectancy < 12 months due to non-cardiac co-morbid conditions Subjects in whom anti-platelet and/or anticoagulant therapy is contraindicated, or who will refuse transfusion Subjects who have active bacterial endocarditis or other active infections Currently participating in an investigational drug or another device study Subjects who have a planned treatment with any other investigational device or procedure during the study follow-up period (90 days) Subject with planned concomitant surgical or transcatheter ablation for Atrial Fibrillation during the study follow-up period (90 days) Any subject with a balloon valvuloplasty (BAV) within 30 days of the procedure Neurologic Subject had active major psychiatric disease Subject has severe visual, auditory, or learning impairment and who are unable to comprehend English and therefore unable to be consented for the study Subjects with neurodegenerative or other progressive neurological disease or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities Angiographic Excessive tortuosity in the right radial/brachial/subclavian artery preventing Sentinel System access and insertion Subject whose brachiocephalic or left carotid artery reveals significant stenosis, calcification, ectasia, dissection, or aneurysm at the ostium or within 3 cm of the ostium Magnetic Resonance Imaging Subject Body Mass Index (BMI) precluding imaging in scanner Contraindications to MRI (subjects with any implantable temporary or permanent pacemaker or defibrillator, metal implants in field of view, metallic fragments, clips, or devices in the brain or eye before TAVR procedure) Planned implantation of a pacemaker or defibrillator implantation after TAVR Claustrophobia Known allergy to gadolinium or contrast agent

Ages Eligible for Study
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Minimum Age: 18 Years

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Arm<br> | Device: Cerebral Protection System-The SENTINEL System with TAVR<br>* Claret Medical Sentinel Cerebral Protection System is intended for use as an embolic protection system to contain and remove embolic material (thrombus/debris) that may enter the carotid arteries.<br>* Other names: TAVR Device: Edwards SAPIEN THV or Edwards SAPIEN XT;|
| Active Comparator: Control Arm<br> | Device: TAVR<br> <br> * Other names: TAVR: Edwards SAPIEN THV or Edwards SAPIEN XT;|
| Other: Safety Arm<br> | Device: Cerebral Protection System-The SENTINEL System with TAVR<br>* Claret Medical Sentinel Cerebral Protection System is intended for use as an embolic protection system to contain and remove embolic material (thrombus/debris) that may enter the carotid arteries.<br>* Other names: TAVR Device: Edwards SAPIEN THV or Edwards SAPIEN XT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Median Total New Lesion Volume in Protected Territories Between Test and Control Arms as Assessed by DW-MRI at Day 2-7 Post-procedure. | Total new lesion volume is defined as the sum of all diffusion-positive new cerebral lesions in post-TAVR DW-MRI relative to the pre-TAVR DW-MRI scans. Protected territories are defined as brain territories uniquely perfused by the vessels protected by the Sentinel System, namely the left and right carotid arteries, and the right vertebral artery. | Day 2-7 Post-Procedure | 
| Patients With Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 Days | Primary Safety Endpoint: MACCE (all death, all stroke, and acute kidney injury class 3 within 72 hours or discharge, whatever occurs first) at 30 days compared to a historical performance goal of 18.3%. | 30 Days Post-Procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Captured Debris Histopathology (Observational) |  | Post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Embolic Protection, Edwards SAPIEN THV, Edwards SAPIEN XT, TAVR, Transfemoral, Transapical, Heart Valve Diseases, Heart Diseases, TAVI, Aortic Stenosis, Aortic Valve, Transcatheter Heart Valve