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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 560
- 主要终点
- Primary Efficacy Endpoint
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
This is a single-blind study. The following individuals will be blinded to the subject's treatment allocation:
Site personnel administering neurological evaluations DW-MRI Core Laboratory personnel performing imaging analyses
While subjects and their family members will not be blinded, they should not be explicitly informed of their treatment group assignment to minimize the risk of inadvertent unblinding of site personnel administering neurological evaluations.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Primary Efficacy Endpoint
时间窗: Evaluated at 72 hours post-procedure (TAVR)
The primary efficacy endpoint is neuroprotection efficacy, determined by pair-wise comparisons among all subjects (Finkelstein-Schoenfeld \[FS\] method1) according to the following prespecified hierarchy of adverse outcomes: * Ischemic stroke (disabling or non-disabling) \[evaluated at 72 hours post-procedure\] * Total lesion volume by DW-MRI \[evaluated at 24-36 hours post-procedure\]
Primary Safety Endpoint
时间窗: Evaluated at 30-day post-procedure (TAVR) follow-up visit
The primary safety endpoint is Major Adverse Events, defined as the composite of the following components at 30 days: * All-cause mortality * All stroke (disabling and non-disabling) * Acute kidney injury (Stage 3)
次要结局
- Combined Safety and Efficacy(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)(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)(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)(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)(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)(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)(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(Evaluated 24-36 hours post-procedure)
- Imaging Endpoints: Total supra-threshold cerebral ischemic lesion volume(Evaluated 24-36 hours post-procedure)
- Imaging Endpoints: Presence of new post-procedure cerebral ischemic lesions(Evaluated 24-36 hours post-procedure)
- Imaging Endpoints: Number of new post-procedure cerebral ischemic lesions(Evaluated 24-36 hours post-procedure)
- Imaging Endpoints: Average new lesion volume(Evaluated 24-36 hours post-procedure)
- Imaging Endpoints: Largest per-subject single lesion(Evaluated 24-36 hours post-procedure)
- Pathology Measures: Debris capture as the average number of captured particles ≥150 µm in diameter(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Pathology Measures: Gross and histologic evaluation of captured debris(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Neurocognitive Measures: NIHSS worsening(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.])
- Neurocognitive Measures: MoCA worsening(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.])
- Secondary Device Performance Endpoints: Successful device deployment(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Secondary Device Performance Endpoints: Successful device positioning(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Secondary Device Performance Endpoints: Successful device retrieval(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Secondary Device Performance Endpoints: Device success(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Secondary Device Performance Endpoints: Procedure success(Evaluated at the time of the TAVR procedure (during the intervention/procedure))