Neuroprotection in Patients Undergoing Aortic Valve Replacement

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of embolic protection devices to reduce ischemic brain injury in patients undergoing surgical aortic valve replacement (AVR).

Detailed Description
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This is a multicenter randomized trial in which patients diagnosed with calcific aortic stenosis (AS) with planned AVR will be randomized to 1) the treatment arm of the Edwards Life Science filter and cannula or the filter as a stand alone with any cannula or 2) to the treatment arm of the CardioGard cannula versus 3) standard care in a 1:1:1 ratio.

Official Title
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Neuroprotection In Patients Undergoing Aortic Valve Replacement

Conditions
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Stroke, Aortic Stenosis, Brain Infarction, Cerebrovascular Accident

Intervention / Treatment
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* Device: Embol-X Embolic Protection Device
* Device: CardioGard Cannula


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 60 years Planned and scheduled surgical aortic valve replacement via a full or minimal-access sternotomy (using central aortic perfusion cannulae) for calcific aortic stenosis with a legally marketed valve No evidence of neurological impairment as defined by a NIHSS ≤1 and modified Rankin scale (mRS) ≤ 2 within 7 days prior to randomization Ability to provide informed consent and comply with the protocol Exclusion Criteria: Contraindication to legally marketed embolic protection devices (e.g. aneurysm of the ascending aorta, aortic trauma, porcelain aorta, known sensitivity to heparin) History of clinical stroke within 3 months prior to randomization Cardiac catheterization within 3 days of the planned aortic valve replacement Cerebral and or aortic arch arteriography or interventions within 3 days of the planned aortic valve replacement Active endocarditis at time of randomization Anticipated inability to tolerate or contraindication for MRI (e.g., known intolerance of MRI, permanent pacemaker at baseline or expected implantation of a permanent pacemaker) Any other concomitant aortic procedure such as root replacement Concomitant surgical procedures other than CABG, mitral annuloplasty, left atrial appendage (LAA) excision or exclusion, atrial septal defect (ASD) closure or patent foramen ovale (PFO) closure Clinical signs of cardiogenic shock or treatment with IV inotropic therapy prior to randomization Concurrent participation in an interventional (drug or device) trial

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Embol-X Embolic Protection Device<br>The surgeon may use either the EMBOL-X® Access Device/Aortic Cannula or a standard cannula with the EMBOL-X® filter deployed through a separate introducer sheath. | Device: Embol-X Embolic Protection Device<br>* per the manufacturer's instructions for use (IFU).<br>* Other names: Edwards Embol-X embolic protection device;|
| Active Comparator: CardioGard Cannula<br>The Cardiogard embolic protection device is a curved tip 24-French aortic perfusion cannula. | Device: CardioGard Cannula<br>* CardioGard Cannula, per the manufacturer's instructions for use (IFU).<br>* Other names: CardioGard Emboli Protection Cannula;|
| No Intervention: Standard Cannula<br>Patients in this arm will receive the standard of care surgical procedure using a cannula of the surgeon's choosing. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Freedom From Clinical or Radiographic Central Nervous System (CNS) Infarction | freedom from CNS infarction, defined as brain, spinal cord, or retinal cell death attributable to ischemia based on neuropathological, neuroimaging, or clinical evidence of permanent injury based on symptoms persisting > 24 hours, with overt symptoms or no known symptoms. All patients will be assessed by 1.5 T (3.0 T is acceptable if 1.5 T not available) Diffusion-weighted imaging (DWI) at 7 (± 3) days post procedure for presence of brain lesions and to measure the number and volume of any present lesions. | up to 10 days post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Composite Endpoint of Mortality, Clinical Stroke, and Acute Kidney Injury | The number of patients who have had a clinical ischemic stroke, acute kidney injury (AKI), or death within 30 days of surgery. | up to 30 days | 
| Number of Patients With Clinically Apparent Stroke at 7 Days | The number of patients who experience a clinically apparent stroke by 7 days post-op | at 7 days | 
| Presence of Radiographic Infarcts | The proportion of patients with radiographic infarcts on day 7 (+/-3 days) MRI. Presences of radiographic infarcts were measured using diffusion-weighted 1.5 or 3T MRI scanners | up to 10 days | 
| Total Infarct Volume | Total infarct volume measured on day 7 dwMRI. | Day 7 | 
| Decline in Overall Neurocognition | Decline in neurocognitive function at 90 days as compared to baseline. Decline defined as the number of patients whose Z score (computed relative to the study population at baseline, adjusting for age, education and sex) at day 90 had decreased by 0.5 SD relative to the baseline score. | baseline and 90 days | 
| Decline in Neurocognitive Function in the Verbal Memory Domain at 90 Days | Decline in neurocognitive function in the verbal memory domain at 90 days as compared to baseline. Decline defined as the number of patients whose Z score (computed relative to the study population at baseline, adjusting for age, education and sex) at day 90 had decreased by 0.5 SD relative to the baseline score. | baseline and 90 days | 
| Decline in Neurocognitive Function in the Visual Memory Domain at 90 Days | Decline in neurocognitive function in the visual memory domain at 90 days as compared to baseline. Decline defined as the number of patients whose Z score (computed relative to the study population at baseline, adjusting for age, education and sex) at day 90 had decreased by 0.5 SD relative to the baseline score. | baseline and 90 days | 
| Decline in Neurocognitive Function in the Executive Function Domain at 90 Day | Decline in neurocognitive function in the executive function domain at 90 days as compared to baseline. Decline defined as the number of patients whose Z score (computed relative to the study population at baseline, adjusting for age, education and sex) at day 90 had decreased by 0.5 SD relative to the baseline score. | baseline and 90 days | 
| Decline in Neurocognitive Function in the Visuospatial/Constructional Praxis Domain at 90 Days | Decline in neurocognitive function in the visuospatial/constructional praxis domain at 90 days as compared to baseline. Decline defined as the number of patients whose Z score (computed relative to the study population at baseline, adjusting for age, education and sex) at day 90 had decreased by 0.5 SD relative to the baseline score. | baseline and 90 days | 
| Decline in Neurocognitive Function in the Auditory-Verbal Simple Attention Domain at 90 Days | Decline in neurocognitive function in the Auditory-Verbal Simple attention domain at 90 days as compared to baseline. Decline defined as the number of patients whose Z score (computed relative to the study population at baseline, adjusting for age, education and sex) at day 90 had decreased by 0.5 SD relative to the baseline score. | baseline and 90 days | 
| Decline in Neurocognitive Function in the Visuomotor/Information Processing Speed Domain at 90 Days | Decline in neurocognitive function in the Visuomotor/Information Processing Speed domain at 90 days as compared to baseline. Decline defined as the number of patients whose Z score (computed relative to the study population at baseline, adjusting for age, education and sex) at day 90 had decreased by 0.5 SD relative to the baseline score. | baseline and 90 days | 
| Modified Rankin Scale >2 at 90 Days | The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms. - No significant disability. Able to carry out all usual activities, despite some symptoms. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. - Moderate disability. Requires some help, but able to walk unassisted. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. - Dead. | 90 days | 
| Barthel Index <= 80 | An overall score has full range from 0 to 100, with higher scores indicating greater independence. | 90 days | 
| Number of Participants With Confusion Assessment Method (CAM) Delirium Assessment at 7 Days |  | 7 days | 
| Mortality by 90 Days | Incidence of all-cause mortality | up to 90 days | 
| Length of Stay for Index Hospitalization |  | up to 90 days | 
| Hospital Readmissions | Rate of hospital readmissions | up to 90 days | 
| Quality of Life - Physical Health Composite | Quality of Life - Physical Health Composite Assessed by Short Form-12 (SF-12). Score ranking from 0 (worst health) to 100 (best health) calculated as the weighted sum of the questions. health scores then transformed into a t-score on the assumption that each question carries equal weight and were standardized to have mean of 50 and standard deviation of 10. | at 90 days | 
| Quality of Life - Mental Health Composite | Quality of life - Mental health composite Assessed by Short Form-12 (SF-12). Score ranking from 0 (worst health) to 100 (best health) calculated as the weighted sum of the questions. health scores then transformed into a t-score on the assumption that each question carries equal weight and were standardized to have mean of 50 and standard deviation of 10. | at 90 days | 
| Number of Participants With Emboli Captured | Assessed by the presence of any debris captured in filter of embolic protection device | day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Embolic Protection Device, Stroke, Brain Infarction, atheroma, Aortic Valve Replacement