Evaluation of Safety and Effectiveness of the EMBLOK EPS Compared With No Cerebral Embolic Protection During TAVR

Official title

A Prospective, Randomized, Multicenter Evaluation of the Safety and Effectiveness of the EMBLOK™ Embolic Protection System Compared With No Cerebral Embolic Protection During Transcatheter Aortic Valve Replacement

Overview

The objective of the study is to evaluate the safety, effectiveness, and performance of the EMBLOK EPS during TAVR by randomized comparison with TAVR without embolic protection (unprotected TAVR). 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 560 subjects undergoing TAVR at up to 40 investigational sites in the United States. All subjects will undergo clinical follow-up (including detailed neurological assessments) in-hospital and at 30 days, and diffusion-weighted magnetic resonance imaging (DW-MRI) follow-up at 24 to 36 hours post-procedure.

Detailed description

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 TAVR without embolic protection (unprotected TAVR).

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 560 subjects undergoing TAVR at up to 40 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 80 subjects total), who will not be randomized but will receive the EMBLOK EPS during TAVR.

In the randomized cohort, up to 480 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 -Unprotected TAVR

All subjects will undergo clinical follow-up (including detailed neurological assessments) in-hospital and at 30 days, and diffusion-weighted magnetic resonance imaging (DW-MRI) follow-up at 24 to 36 hours post-procedure.

Interventions

• Device EMBLOK™ Embolic Protection System ("EMBLOK EPS")
  The EMBLOK EPS is intended to capture and remove thrombus/debris while performing transcatheter aortic valve replacement procedures.

Primary outcome measures

• Primary Efficacy Endpoint [Time frame: Evaluated at 72 hours post-procedure (TAVR)]
• Primary Safety Endpoint [Time frame: Evaluated at 30-day post-procedure (TAVR) follow-up visit]

Secondary outcome measures (12)

• Combined Safety and Efficacy [Time frame: Evaluated post-procedure (day 1), in-hospital (defined as 7 days post-procedure or immediately prior to discharge from the index procedure hospitalization, whichever occurs first)]
• Mortality (VARC-2 defined) [Time frame: Evaluated immediately after the intervention/procedure, up until discharge from hospital or up until 7 days post procedure, which ever occurs first.]
• Neurological Events (VARC-2 and NeuroARC defined) [Time frame: Evaluated immediately after the intervention/procedure, up until discharge from hospital or up to 7 days post-procedure, and at the 30 day follow-up visit.]
• Incidence of acute kidney injury (AKIN classification) [Time frame: Evaluated immediately after the intervention/procedure, up until discharge from hospital or up to 7 days post-procedure, and at the 30 day follow-up visit.]]
• Incidence of major vascular complications (VARC-3 defined) [Time frame: Evaluated immediately after the intervention/procedure, up until discharge from hospital or up to 7 days post-procedure, and at the 30 day follow-up visit.]]
• Incidence of life-threatening or disabling bleeding and major bleeding (VARC-2 defined) [Time frame: Evaluated immediately after the intervention/procedure, up until discharge from hospital or up to 7 days post-procedure, and at the 30 day follow-up visit.]
• Major adverse embolic events (MAEE) [Time frame: Evaluated immediately after the intervention/procedure, up until discharge from hospital or up until 7 days post procedure, which ever occurs first.]]
• Imaging Endpoints: Total volume of new post-procedure cerebral ischemic lesions [Time frame: Evaluated 24-36 hours post-procedure]
• Imaging Endpoints: Total supra-threshold cerebral ischemic lesion volume [Time frame: Evaluated 24-36 hours post-procedure]
• Imaging Endpoints: Presence of new post-procedure cerebral ischemic lesions [Time frame: Evaluated 24-36 hours post-procedure]
• Imaging Endpoints: Number of new post-procedure cerebral ischemic lesions [Time frame: Evaluated 24-36 hours post-procedure]
• Imaging Endpoints: Average new lesion volume [Time frame: Evaluated 24-36 hours post-procedure]

Eligibility criteria

Clinical Eligibility Criteria:

Clinical Inclusion Criteria:

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

• Subject is ≥ 18 years of age.
• Subject meets FDA approved indications for TAVR using an iliofemoral approach with a commercially approved transcatheter heart valve.
• Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to the index study procedure.
• Subject agrees to comply with all protocol-specified procedures and assessments.
• Subject or subject's legal representative signs an IRB/EC approved informed consent form prior to study participation.

Clinical Exclusion Criteria:

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

• Subjects with hepatic failure (Child-Pugh class C).
• Subjects with hypercoagulable states that cannot be corrected by additional periprocedural heparin.
• Subjects who have a planned treatment with any other investigational device or procedure during the study period.
• 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.
• Subject has experienced an acute myocardial infarction (World Health Organization \[WHO\] criteria) within 30 days of the planned index procedure.
• Subject requires an urgent or emergent TAVR procedure.
• Subjects with renal failure (estimated Glomerular Filtration Rate \[eGFR\] < 30 mL/min by the Modification of Diet in Renal Disease \[MDRD\] formula, or on dialysis).
• 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 (baseline mRS ≥3).
• Subject has an ejection fraction of 30% or less.
• Subject has a sensitivity to contrast media that cannot be adequately pre-treated.
• 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.
• Subject has active endocarditis or an ongoing systemic infection defined as fever with temperature > 38°C and/ or white blood cell > 15,000 IU.
• Subjects undergoing therapeutic thrombolysis.
• Subject has history of bleeding diathesis or a coagulopathy or contraindications to anticoagulation and antiplatelet therapy.
• Subject is known or suspected to be pregnant, or is lactating.
• Subject has contraindications to cerebral MRI (e.g., body habitus that precludes imaging, claustrophobia, implanted non-MRI compatible permanent pacemaker or defibrillator, metallic clips or fragments).
• In the investigator's opinion, the subject has other factors that may cause the subject to be non-compliant with the protocol or confound the data interpretation, such as participating in another drug or device clinical study, or other medical illness.

General Anatomic Exclusion Criteria

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

• Non-iliofemoral approach 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).
• 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).
• Ascending aorta length (from the brachiocephalic artery takeoff to the most distal edge of the TAVR prosthetic device) less than 3.5 cm.
• 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.
• Subjects with severe peripheral arterial, abdominal aortic, or thoracic aortic disease that precludes delivery sheath vascular access.
• Subjects in whom the aortic arch is heavily calcified, severely atheromatous, or severely tortuous.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07129421 · CLP 002-2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗