To study the effect of the use of the LV 1 System with the Sentinel System, during TAVR, with respect to procedure-related cerebral embolic burden in patients assessed by DW-MRI. To limit data variability and avoid confounding effects of different…
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint:
Acute cerebral embolic burden reduction after TAVI assessed with 1.5-tesla
DW-MRI at Day 2-4 compared to baseline
Secondary outcome
Secondary Endpoints:
* MACCE @ 30 days
* Histopathology (proximal, distal, LV1 Filter)
* Neurological examinations, National Institutes of Health Stroke Scale (NIHSS)
and Modified Rankin (mRS)
* LV1 System Success
Major Adverse Cardiac and Cerebrovascular Events (MACCE) is comprised of the
following:
* All-cause mortality
* All stroke (major, minor, TIA)
* Acute Kidney Injury (Class 3)
Background summary
Stroke remains a major complication for transcatheter aortic valve replacement
(TAVI) which has been reported to increase mortality 3-fold .
Diffusion-weighted magnetic resonance imaging (DW-MRI) can detect and evaluate
quality, quantity and fate of cerebral embolism with subsequent acute ischemic
cerebral lesions within the brain hemispheres, brain stem, and cerebellum. This
technique serves as an emerging surrogate endpoint for clinical and subclinical
ischemic stroke and has been used frequently to quantify thromboembolism
associated with TAVI.
The Claret Medical Sentinel Cerebral Protection System was developed to protect
the brain from injury caused by embolic debris. The device includes two
conically shaped polyurethane filters with 140 micron holes, mounted onto
nitinol self-expanding wire frames. The first filter is deployed in the
brachiocephalic trunk to protect the right carotid artery; and the second
filter is deployed in the left common carotid artery. The Sentinel Cerebral
Protection System is safe and effective in capturing embolic debris in
cardiovascular procedures. The device obtained CE mark approval in 2011. A
recent randomized study (CLEAN-TAVI) demonstrated that theSentinel System is
associated with a significant reduction in the number and volume of cerebral
lesions as determined by Diffusion Weighted-MRI subtraction at 2 and 7 days
after TAVI . In addition, the filter group showed a lower ataxia rate than the
control group (9% vs 24%), indicating the potential to reduce neurologic
complications. However, the Sentinel System does not protect all regions of
the brain.
The LV1 System (investigational product) provides additional cerebral
protection to unprotected regions of the brain. This product is similar to the
Sentinel System, but is intended to be placed into in the left subclavian
artery to provide protection for its branches, and in particular, the left
vertebral artery (which supplies approximately 10% of the brain blood flow).
This is expected to result in a further reduction in cerebral embolic burden.
To evaluate the hypothesis, that using Sentinel in combination with LV1 filter
provides more complete protection of the brain, the present 3 arm controlled
randomized study is designed to quantify embolic burden reduction (with
Diffusion Weighted-MRI) in patients treated with the Sentinel System alone and
with the Sentinel System in combination with LV1 System versus TAVI without any
embolic protection.
Study objective
To study the effect of the use of the LV 1 System with the Sentinel System,
during TAVR, with respect to procedure-related cerebral embolic burden in
patients assessed by DW-MRI. To limit data variability and avoid confounding
effects of different TAVI devices, patients enrolled will be those expected to
receive only one type of TAVI device (Boston Scientific Lotus Valve System, a
next generation repositionable device).
The study population is comprised of subjects with severe native aortic valve
stenosis who meet the commercially approved indications for TAVI and comply
with the inclusion/exclusion criteria of the study.
Study design
Multicenter, prospective, randomized (1:1:1), open label
Treatment Arm #1: TF-TAVI with the Sentinel System and the LV1 filter
Control Arm #2: TF-TAVI without any embolic protection (primary analysis)
Control Arm #3: TF-TAVI with the Sentinel System only (secondary analysis for
pilot assessment)
This study is expected to enroll a total of 72 subjects, in two phases:
- Phase 1: Total of 36 randomized (12:12:12) subjects
- Phase 2 (After interim analysis of results): Total of 36 additional
randomized (12:12:12) subjects may be enrolled
Intervention
The LV1 System (investigational product) provides additional cerebral
protection to unprotected regions of the brain. This product is similar to the
Sentinel System, but is intended to be placed into in the left subclavian
artery to provide protection for its branches, and in particular, the left
vertebral artery. This is expected to result in a further reduction in embolic
burden.
The LV1 System is a filter catheter, sheathed inside a commercially available 5
Fr multipurpose guidecatheter and is intended to be inserted through the left
radial or left brachial artery and advanced to the junction of the left
subclavian artery and the aorta where the filter is deployed. The filter is
suitable for left subclavian vessels with diameters of 7 * 12mm.
During a TAVI procedure, arterial pressure is commonly monitored through a
sheath placed in the left radial artery that is filled with saline and
connected to an external extra-vascular blood pressure transducer. In this
study, the left radial access site will be used for the LV1 System, and so in
order to maintain the ability for arterial pressure to be monitored through the
left radial artery, the LV1 System has been designed to allow pressure
monitoring through the required multipurpose guidecatheter using the same
external extra-vascular blood pressure transducer. Once the filter is deployed
in the left subclavian artery, the central saline-filled lumen of the
guidecatheter is used to transmit the pressure signal to the external pressure
transducer connected to the side branch of the required Y-connector, in exactly
the same manner as is done during TAVI procedures that do not use the LV1
System for embolic protection.
Study burden and risks
The risks and benefits associated with cerebral embolic protection devices,
including their use in endovascular procedures such as TAVI , are well
documented as these devices have a long history of clinical use.
The Sentinel System is CE Marked (CE 606742) and approved for marketing in the
European Community. The clinical data collected for the Sentinel System
demonstrate the Cerebral Protection System has a strong safety profile. The
characteristics of the LV1 System are the same as the Sentinel System, with the
addition of the possibility that arterial pressure may be monitored through the
LV1 System.
The potential benefit of use of the LV1 System, in conjunction with the
Sentinel System, is a further reduction in the acute cerebral embolic burden
(i.e. cumulative number and volume of diffusion-positive brain lesions) as
detected with DW-MRI given that approximately 10% of the cerebral blood supply
flows through the left vertebral artery .
Recent studies have shown new lesions detected by DW-MRI in 68-91% of TAVI
patients and a significant reduction in number and volume of cerebral lesions
were reported where the Claret Medical Cerebral Protection System was used.
Without the Sentinel and the LV1 Systems, embolic debris could otherwise travel
unimpeded via the cerebral circulation to the brain and could lead to cerebral
vascular events.
Copperhill Parkway Suite 1
CA 95403 Santa Rosa
US
Copperhill Parkway Suite 1
CA 95403 Santa Rosa
US
Listed location countries
Age
Inclusion criteria
1. Severe symptomatic aortic valve stenosis
2. Compatible anatomy for Sentinel and LV1 Systems:
o Sentinel System: left common carotid artery (6.5 * 10 mm) and brachiocephalic artery (9 * 15 mm) diameters
o LV1 System: left subclavian artery (7.0 * 12.0 mm) diameter
3. Subject eligible for transfemoral TAVI access with planned implantation of Boston Scientific Lotus Valve System
Exclusion criteria
1. Contraindications to TAVI per heart team
2. Current or recent cerebrovascular accident (stroke, TIA) <6 months
3. Transapical, direct aortic or subclavian TAVI access
4. Carotid stenting or endarterectomy in last 6 weeks
5. Symptomatic or asymptomatic severe occlusive carotid disease requiring concomitant Carotid Endarterectomy / stenting
6. History of atrial fibrillation (AF) including:
o Persistent AF (defined as continuous AF which is sustained beyond seven days, or lasting greater than 48 hours and less than seven days but necessitating pharmacologic or electrical cardioversion), or
o History of Paroxysmal AF during the previous 30 days. Paroxysmal AF is defined as recurrent AF (>2 episodes) that terminates spontaneously within 7 days. Episodes of AF of < 48 hours* duration that are terminated with electrical or pharmacologic cardioversion are also classified as paroxysmal AF episodes.;7. Subject with active endocarditis or other systemic infection
8. Prior aortic valve replacement
9. Concomitant procedure with TAVI such as CABG, PCI, etc.
10. Claustrophobia
11. Contraindications to MRI (subjects with any non-MRI compatible 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 non-MRI compatible pacemaker or implantable cardioverter defibrillator after TAVR
12. Allergy to intravascular contrast agents
13. Immobilization or other morbidity with life expectancy < 1 year
14. Inability to accommodate a 6F sheath (Sentinel) or 5F (LV1) into the right and left radial or brachial arteries respectively
15. Inadequate circulation to the right or left extremity as evidenced by signs of artery occlusion (modified Allen*s test) or absence of radial/brachial pulse
16. Subjects with vascular tortuosity or anatomy that would preclude the safe introduction and placement of the Sentinel System and/or the LV1 System per anatomy screening process
17. Lack of written informed consent
18. Patients in whom anticoagulant and antiplatelet therapy is contraindicated
19. Patients with uncorrected bleeding disorders
20. Patients with compromised blood flow to the left upper extremity
21.Patient who has arterial stenosis >70% in the left subclavian artery
22.Patient whose left subclavian artery reveals significant stenosis, ectasia, dissection, or aneurysm between the aortic ostium and the left vertebral artery
23. Patient is pregnant or lactating
24. Patients requiring left axillary/subclavian access for transcatheter aortic valve implantation
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL53344.078.15 |