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).
Brief Title
Neuroprotection in Patients Undergoing Aortic Valve Replacement
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Aortic Stenosis
Brain Infarction
Cerebrovascular Accident
Stroke
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
Embolic Protection Device
Stroke
Brain Infarction
atheroma
Aortic Valve Replacement
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
60 Years
NCT Id
NCT02389894
Org Class
Other
Org Full Name
Icahn School of Medicine at Mount Sinai
Org Study Id
GCO 08-1078-0009
Overall Status
Completed
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Neuroprotection In Patients Undergoing Aortic Valve Replacement
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percentage of Participants With Freedom From Clinical or Radiographic Central Nervous System (CNS) Infarction
Outcome Time Frame
up to 10 days post procedure
Secondary Ids
Secondary Id
2U01HL088942-07
Secondary Outcomes
Outcome Description
The number of patients who have had a clinical ischemic stroke, acute kidney injury (AKI), or death within 30 days of surgery.
Outcome Time Frame
up to 30 days
Outcome Measure
Number of Participants With a Composite Endpoint of Mortality, Clinical Stroke, and Acute Kidney Injury
Outcome Description
The number of patients who experience a clinically apparent stroke by 7 days post-op
Outcome Time Frame
at 7 days
Outcome Measure
Number of Patients With Clinically Apparent Stroke at 7 Days
Outcome Description
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
Outcome Time Frame
up to 10 days
Outcome Measure
Presence of Radiographic Infarcts
Outcome Description
Total infarct volume measured on day 7 dwMRI.
Outcome Time Frame
Day 7
Outcome Measure
Total Infarct Volume
Outcome Description
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.
Outcome Time Frame
baseline and 90 days
Outcome Measure
Decline in Overall Neurocognition
Outcome Description
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.
Outcome Time Frame
baseline and 90 days
Outcome Measure
Decline in Neurocognitive Function in the Verbal Memory Domain at 90 Days
Outcome Description
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.
Outcome Time Frame
baseline and 90 days
Outcome Measure
Decline in Neurocognitive Function in the Visual Memory Domain at 90 Days
Outcome Description
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.
Outcome Time Frame
baseline and 90 days
Outcome Measure
Decline in Neurocognitive Function in the Executive Function Domain at 90 Day
Outcome Description
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.
Outcome Time Frame
baseline and 90 days
Outcome Measure
Decline in Neurocognitive Function in the Visuospatial/Constructional Praxis Domain at 90 Days
Outcome Description
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.
Outcome Time Frame
baseline and 90 days
Outcome Measure
Decline in Neurocognitive Function in the Auditory-Verbal Simple Attention Domain at 90 Days
Outcome Description
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.
Outcome Time Frame
baseline and 90 days
Outcome Measure
Decline in Neurocognitive Function in the Visuomotor/Information Processing Speed Domain at 90 Days
Outcome Description
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.
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.
Outcome Time Frame
90 days
Outcome Measure
Modified Rankin Scale >2 at 90 Days
Outcome Description
An overall score has full range from 0 to 100, with higher scores indicating greater independence.
Outcome Time Frame
90 days
Outcome Measure
Barthel Index <= 80
Outcome Time Frame
7 days
Outcome Measure
Number of Participants With Confusion Assessment Method (CAM) Delirium Assessment at 7 Days
Outcome Description
Incidence of all-cause mortality
Outcome Time Frame
up to 90 days
Outcome Measure
Mortality by 90 Days
Outcome Time Frame
up to 90 days
Outcome Measure
Length of Stay for Index Hospitalization
Outcome Description
Rate of hospital readmissions
Outcome Time Frame
up to 90 days
Outcome Measure
Hospital Readmissions
Outcome Description
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.
Outcome Time Frame
at 90 days
Outcome Measure
Quality of Life - Physical Health Composite
Outcome Description
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.
Outcome Time Frame
at 90 days
Outcome Measure
Quality of Life - Mental Health Composite
Outcome Description
Assessed by the presence of any debris captured in filter of embolic protection device
Outcome Time Frame
day 1
Outcome Measure
Number of Participants With Emboli Captured
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
60
Investigators
Investigator Type
Principal Investigator
Investigator Name
Robert Michler
Investigator Email
RMICHLER@MONTEFIORE.ORG
Investigator Phone
rmichler