Neuroprotection in Patients Undergoing Aortic Valve Replacement

Not Applicable

Completed

Conditions: Stroke
Aortic Stenosis
Cerebrovascular Accident
Brain Infarction

Interventions: Device: Embol-X Embolic Protection Device
Device: CardioGard Cannula

Registration Number: NCT02389894

Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 383

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Embol-X Embolic Protection Device	Embol-X Embolic Protection Device	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.
CardioGard Cannula	CardioGard Cannula	The Cardiogard embolic protection device is a curved tip 24-French aortic perfusion cannula.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Freedom From Clinical or Radiographic Central Nervous System (CNS) Infarction	up to 10 days post procedure	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.

Secondary Outcome Measures

Name	Time	Method
Total Infarct Volume	Day 7	Total infarct volume measured on day 7 dwMRI.
Decline in Overall Neurocognition	baseline and 90 days	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.
Number of Participants With a Composite Endpoint of Mortality, Clinical Stroke, and Acute Kidney Injury	up to 30 days	The number of patients who have had a clinical ischemic stroke, acute kidney injury (AKI), or death within 30 days of surgery.
Number of Patients With Clinically Apparent Stroke at 7 Days	at 7 days	The number of patients who experience a clinically apparent stroke by 7 days post-op
Presence of Radiographic Infarcts	up to 10 days	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
Decline in Neurocognitive Function in the Visuospatial/Constructional Praxis Domain at 90 Days	baseline and 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.
Quality of Life - Physical Health Composite	at 90 days	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.
Decline in Neurocognitive Function in the Verbal Memory Domain at 90 Days	baseline and 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.
Decline in Neurocognitive Function in the Visual Memory Domain at 90 Days	baseline and 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.
Decline in Neurocognitive Function in the Executive Function Domain at 90 Day	baseline and 90 days	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.
Decline in Neurocognitive Function in the Auditory-Verbal Simple Attention Domain at 90 Days	baseline and 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.
Decline in Neurocognitive Function in the Visuomotor/Information Processing Speed Domain at 90 Days	baseline and 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.
Number of Participants With Confusion Assessment Method (CAM) Delirium Assessment at 7 Days	7 days
Modified Rankin Scale >2 at 90 Days	90 days	The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms. 1. - No significant disability. Able to carry out all usual activities, despite some symptoms. 2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3. - Moderate disability. Requires some help, but able to walk unassisted. 4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6. - Dead.
Quality of Life - Mental Health Composite	at 90 days	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.
Barthel Index <= 80	90 days	An overall score has full range from 0 to 100, with higher scores indicating greater independence.
Hospital Readmissions	up to 90 days	Rate of hospital readmissions
Mortality by 90 Days	up to 90 days	Incidence of all-cause mortality
Length of Stay for Index Hospitalization	up to 90 days
Number of Participants With Emboli Captured	day 1	Assessed by the presence of any debris captured in filter of embolic protection device

Trial Locations

Locations (18): Dartmouth-Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
University of Virginia
🇺🇸
Charlottesville, Virginia, United States
Montefiore Einstein Heart Center
🇺🇸
Bronx, New York, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
🇨🇦
Quebec, Canada
University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
Baylor Research Institute
🇺🇸
Plano, Texas, United States
Montreal Heart Institute
🇨🇦
Montreal, Quebec, Canada
University of Southern California
🇺🇸
Los Angeles, California, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
University of Maryland
🇺🇸
Baltimore, Maryland, United States
NIH Heart Center at Suburban Hospital
🇺🇸
Bethesda, Maryland, United States
Duke University
🇺🇸
Durham, North Carolina, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
Mission Hospital
🇺🇸
Asheville, North Carolina, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
Toronto General Hospital
🇨🇦
Toronto, Ontario, Canada