A Prospective, Randomized, Multicenter Evaluation of the Safety and Effectiveness of the EMBLOK Embolic Protection System During Transcatheter Aortic Valve Replacement
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 532
- 试验地点
- 46
- 主要终点
- Debris capture, defined as the average number of captured particles ≥150 µm in diameter, as assessed by independent histologic analysis
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 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.
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 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.
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
- Double (Participant, Outcomes Assessor)
盲法说明
This is a single-blind study. The following individuals will be blinded to the subject's treatment allocation:
- The subject and his or her family members
- Site personnel administering neurological evaluations
- Pathology Core Laboratory personnel performing debris analyses
Un-blinding will occur only after the database has been locked for the analysis of the primary endpoint or to protect subject rights, welfare, or well-being at the request of the DMC. A site investigator may also reveal treatment allocation to an individual subject if deemed necessary due to complication or injury.
入排标准
- 年龄范围
- 18 Years 至 90 Years（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 between 18 and 90 years of age.
- •Subject meets FDA approved indications for TAVR procedure on a native aortic valve 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 48 hours 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 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 a previously implanted aortic or mitral valve bioprosthesis
- •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).
- •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.
- •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 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:
- •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).
- •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 site of filter placement to the aortic root) less than 7.5 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.
- •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):
- •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.
- •Brachiocephalic or carotid vessel with excessive tortuosity.
- •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)
- •Arterial stenosis >70% in either the left common carotid artery or the brachiocephalic artery.
- •Brachiocephalic or left carotid artery reveals significant stenosis, ectasia, dissection, or aneurysm at the aortic ostium or within 3 cm of the aortic ostium.
结局指标
主要结局
Debris capture, defined as the average number of captured particles ≥150 µm in diameter, as assessed by independent histologic analysis
时间窗: Evaluated at the time of the TAVR procedure (during the intervention/procedure)
The co-primary filtration efficacy endpoint is debris capture, defined as the average number of captured particles ≥150 μm in diameter, as assessed by independent histologic analysis.
Incidence of the composite of all-cause mortality, all stroke (disabling or non-disabling) and transient ischemic attack (TIA), and Acute Kidney Injury Stage 2 or 3 (including renal replacement therapy), according to VARC-2 definitions
时间窗: Evaluated at 30-day post-procedure (TAVR) follow-up visit
The primary safety and efficacy endpoint is combined safety and efficacy at 30 days, defined as a composite of the following VARC-2 defined components: * All-cause mortality * All stroke (disabling or non-disabling) and transient ischemic attack (TIA) * Acute Kidney Injury Stage 2 or 3 (including renal replacement therapy)
次要结局
- Incidence of major vascular complications(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.)
- Number of captured particles, as assessed by an independent Pathology Core Laboratory(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Material composition of captured particles, as assessed by an independent Pathology Core Laboratory(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Incidence of stroke (sub-classified as ischemic, hemorrhagic, or undetermined, and as disabling or non-disabling) and TIA, according to VARC-2 and NeuroARC definitions(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: NIHSS assessment(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 all-cause mortality (VARC-2 defined), subclassified as cardiovascular or non-cardiovascular mortality(Evaluated immediately after the intervention/procedure, up until discharge from hospital or up until 7 days post procedure, which ever occurs first.)
- Incidence of acute kidney injury (AKIN classification), subclassified as stage 1, 2, or 3(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.)
- Prevalence of captured embolic debris, as assessed by an independent Pathology Core Laboratory(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- 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.)
- Diameter of captured particles (in mm), as assessed by an independent Pathology Core Laboratory(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Neurocognitive Measures: MoCA assessment(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.)
- Rate of successful retrieval of the intact device(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Incidence of the composite of all-cause mortality, all stroke (disabling or non-disabling) and transient ischemic attack (TIA), and Acute Kidney Injury Stage 2 or 3 (including renal replacement therapy), according to VARC-2 definitions(Evaluated immediately after the intervention/procedure, up until discharge from hospital or up until 7 days post procedure, which ever occurs first.)
- Incidence of the composite of all stroke (disabling or non-disabling) and transient ischemic attack (TIA), and Acute Kidney Injury Stage 2 or 3 (including renal replacement therapy), and systemic embolization(Evaluated immediately after the intervention/procedure, up until discharge from hospital or up until 7 days post procedure, which ever occurs first.)
- Rate of successful deployment, positioning, and retrieval of the device(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Rate of successful device delivery to the site of filter placement and successful deployment of the device(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Rate of successful device positioning followed by maintenance of positioning for the duration of the TAVR procedure, as assessed by an independent Angiographic Core Laboratory(Evaluated at the time of the TAVR procedure (during the intervention/procedure))
- Rate of successful deployment, positioning, and retrieval of the device without embolic protection device-related serious adverse events(Evaluated at the time of the TAVR procedure (during the intervention/procedure))