Evaluation of Safety and Effectiveness of the EMBLOK EPS During TAVR

A Prospective, Randomized, Multicenter Evaluation of the Safety and Effectiveness of the EMBLOK Embolic Protection System During Transcatheter Aortic Valve Replacement

The objective of the study is to evaluate the safety, effectiveness, and performance of the EMBLOK EPS during TAVR by randomized comparison with a commercially available embolic protection device. The targeted study population consists of patients meeting FDA-approved indications for TAVR with commercially available transcatheter heart valve systems.

This prospective, multicenter, single-blind, randomized controlled trial will enroll up to a total of 532 subjects undergoing TAVR at up to 30 investigational sites in the United States. All subjects will undergo clinical follow-up (including detailed neurological assessments) in-hospital and at 30 days.

Embolic stroke remains a major complication for TAVR, resulting in a two-fold increase in 1-year mortality. Embolic protection devices have been developed to filter embolic debris during the procedure, potentially reducing the occurrence of neurologic events associated with TAVR. The EMBLOK EPS may improve on currently available devices by capturing and retrieving debris directed toward all 3 cerebral vessels in the aortic arch as well as the descending aorta.

The objective of the study is to evaluate the safety, effectiveness, and performance of the EMBLOK EPS during TAVR by randomized comparison with a commercially available embolic protection device. With this comparator device, the left subclavian artery and descending aorta are not protected.

The targeted study population consists of patients meeting FDA-approved indications for TAVR with commercially available transcatheter heart valve systems.

This prospective, multicenter, single-blind, randomized controlled trial will enroll up to a total of 532 subjects undergoing TAVR at up to 30 investigational sites in the United States.

Prior to enrollment of the first randomized subject at each site, each site will enroll 2 Roll-In subjects (up to 60 subjects total), who will not be randomized but will receive the EMBLOK EPS during TAVR.

In the randomized cohort, up to 422 subjects meeting eligibility criteria will be randomized 1:1 (stratified by operative risk and study site) to one of two treatment arms:

1. Intervention - EMBLOK EPS during TAVR
2. Control - SENTINEL CPS during TAVR

In addition, a nested registry will enroll up to 50 subjects who meet clinical eligibility criteria and are anatomically suitable for the EMBLOK EPS, but whose anatomy precludes the use of the SENTINEL CPS.

All subjects will undergo clinical follow-up (including detailed neurological assessments) in-hospital and at 30 days.

Clinical Eligibility Criteria:

Clinical Inclusion Criteria:

Subjects must meet ALL the following criteria to be eligible for participation in the study:

1. Subject is between 18 and 90 years of age.
2. Subject meets FDA approved indications for TAVR procedure on a native aortic valve using an iliofemoral approach with a commercially approved transcatheter heart valve.
3. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 48 hours prior to the index study procedure.
4. Subject agrees to comply with all protocol-specified procedures and assessments.
5. Subject or subject's legal representative signs an IRB approved informed consent form prior to study participation.

Clinical Exclusion Criteria:

Subjects will be excluded if ANY of the following criteria apply:

1. Subjects with a previously implanted aortic or mitral valve bioprosthesis
2. Subjects with hepatic failure (Child-Pugh class C).
3. Subjects with hypercoagulable states that cannot be corrected by additional periprocedural heparin.
4. Subjects who have a planned treatment with any other investigational device or procedure during the study period.
5. Subjects planned to undergo any other cardiac surgical or interventional procedure (e.g., concurrent coronary revascularization) during the TAVR procedure or within 10 days prior to the TAVR procedure. NOTE: Diagnostic cardiac catheterization is permitted within 10 days prior to the TAVR procedure.
6. Subject has experienced an acute myocardial infarction (World Health Organization [WHO] criteria) within 30 days of the planned index procedure.
7. Subject requires an urgent or emergent TAVR procedure.
8. Subjects with renal failure (estimated Glomerular Filtration Rate [eGFR] < 30 mL/min by the Modification of Diet in Renal Disease [MDRD] formula).
9. Subject has documented history of stroke or transient ischemic attack within prior 6 months, or any prior stroke with a permanent major disability or deficit.
10. Subject has an ejection fraction of 30% or less.
11. Subject has a sensitivity to contrast media that cannot be adequately pre-treated.
12. Subject has known allergy or hypersensitivity to any embolic protection device materials (e.g., nickel-titanium) or allergy to intravascular contrast agents that cannot be pre-medicated
13. Subject has active endocarditis or an ongoing systemic infection defined as fever with temperature > 38°C and/ or white blood cell > 15,000 IU.
14. Subjects undergoing therapeutic thrombolysis.
15. Subject has history of bleeding diathesis or a coagulopathy or contraindications to anticoagulation and antiplatelet therapy.
16. Subject is known or suspected to be pregnant, or is lactating.
17. Subject is currently participating in another drug or device clinical study, or has other medical illnesses that may cause the subject to be non-compliant with the protocol or confound the data interpretation.

Anatomic Eligibility Criteria:

General Anatomic Exclusion Criteria:

Subjects meeting any of the following criteria will not be eligible for participation in the study:

1. Non-iliofemoral approach for is required for the TAVR system (e.g., trans-axillary, trans-subclavian, trans-brachiocephalic, trans-carotid, trans-apical or trans-aortic access for TAVR is required).
2. Subject peripheral anatomy is not compatible with contralateral iliofemoral access with an 11 French catheter (e.g., due to excessive tortuosity, stenosis, ectasia, dissection, or aneurysm).
3. Ascending aorta length (from the site of filter placement to the aortic root) less than 7.5 cm.
4. Diameter of the aorta at the intended site of Emblok filter deployment proximal to the brachiocephalic artery ostium is less than 25 mm or greater than 40 mm.
5. Subjects with severe peripheral arterial, abdominal aortic, or thoracic aortic disease that precludes delivery sheath vascular access.
6. Subjects in whom the aortic arch is heavily calcified, severely atheromatous, or severely tortuous.

Additional Anatomic Exclusion Criteria:

Subjects with any of the following criteria will be excluded from participation in the Randomized Cohort, but are eligible for participation in the Roll-In and Nested Registry cohorts (provided they meet all other eligibility criteria):

1. Diameters of the arteries at the site of filter placement are < 9 or > 15 mm for the brachiocephalic artery or < 6.5 or >10 mm in the left common carotid.
2. Brachiocephalic or carotid vessel with excessive tortuosity.
3. Compromised blood flow to the right upper extremity, or other conditions that would preclude 6 Fr radial or brachial vascular access (e.g., excessive tortuosity)
4. Arterial stenosis >70% in either the left common carotid artery or the brachiocephalic artery.
5. Brachiocephalic or left carotid artery reveals significant stenosis, ectasia, dissection, or aneurysm at the aortic ostium or within 3 cm of the aortic ostium.