Back to resultsNeuroprotection in Patients Undergoing Aortic Valve Replacement
Primary Purpose
Aortic Stenosis, Brain Infarction, Cerebrovascular Accident
Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Embol-X Embolic Protection Device
CardioGard Cannula
Sponsored by
About this trial
This is an interventional prevention trial for Aortic Stenosis focused on measuring Embolic Protection Device, Stroke, Brain Infarction, atheroma, Aortic Valve Replacement
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
Sites / Locations
- University of Southern California
- Emory University
- University of Maryland
- NIH Heart Center at Suburban Hospital
- Dartmouth-Hitchcock Medical Center
- Montefiore Einstein Heart Center
- Columbia University Medical Center
- Mission Hospital
- Duke University
- Cleveland Clinic Foundation
- Ohio State University
- University of Pennsylvania
- Baylor Research Institute
- University of Virginia
- University of Alberta Hospital
- Toronto General Hospital
- Montreal Heart Institute
- Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
No Intervention
Arm Label
Embol-X Embolic Protection Device
CardioGard Cannula
Standard Cannula
Arm Description
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.
The Cardiogard embolic protection device is a curved tip 24-French aortic perfusion cannula.
Patients in this arm will receive the standard of care surgical procedure using a cannula of the surgeon's choosing.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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
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
Total Infarct Volume
Total infarct volume measured on day 7 dwMRI.
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.
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.
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.
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.
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.
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.
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.
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.
Barthel Index <= 80
An overall score has full range from 0 to 100, with higher scores indicating greater independence.
Number of Participants With Confusion Assessment Method (CAM) Delirium Assessment at 7 Days
Mortality by 90 Days
Incidence of all-cause mortality
Length of Stay for Index Hospitalization
Hospital Readmissions
Rate of hospital readmissions
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.
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.
Number of Participants With Emboli Captured
Assessed by the presence of any debris captured in filter of embolic protection device
Full Information
NCT ID
NCT02389894
First Posted
March 10, 2015
Last Updated
April 26, 2019
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT02389894
Brief Title
Neuroprotection in Patients Undergoing Aortic Valve Replacement
Official Title
Neuroprotection In Patients Undergoing Aortic Valve Replacement
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aortic Stenosis, Brain Infarction, Cerebrovascular Accident, Stroke
Keywords
Embolic Protection Device, Stroke, Brain Infarction, atheroma, Aortic Valve Replacement
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
383 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Embol-X Embolic Protection Device
Arm Type
Active Comparator
Arm Description
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.
Arm Title
CardioGard Cannula
Arm Type
Active Comparator
Arm Description
The Cardiogard embolic protection device is a curved tip 24-French aortic perfusion cannula.
Arm Title
Standard Cannula
Arm Type
No Intervention
Arm Description
Patients in this arm will receive the standard of care surgical procedure using a cannula of the surgeon's choosing.
Intervention Type
Device
Intervention Name(s)
Embol-X Embolic Protection Device
Other Intervention Name(s)
Edwards Embol-X embolic protection device
Intervention Description
per the manufacturer's instructions for use (IFU).
Intervention Type
Device
Intervention Name(s)
CardioGard Cannula
Other Intervention Name(s)
CardioGard Emboli Protection Cannula
Intervention Description
CardioGard Cannula, per the manufacturer's instructions for use (IFU).
Primary Outcome Measure Information:
Title
Percentage of Participants With Freedom From Clinical or Radiographic Central Nervous System (CNS) Infarction
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.
Time Frame
up to 10 days post procedure
Secondary Outcome Measure Information:
Title
Number of Participants With a Composite Endpoint of Mortality, Clinical Stroke, and Acute Kidney Injury
Description
The number of patients who have had a clinical ischemic stroke, acute kidney injury (AKI), or death within 30 days of surgery.
Time Frame
up to 30 days
Title
Number of Patients With Clinically Apparent Stroke at 7 Days
Description
The number of patients who experience a clinically apparent stroke by 7 days post-op
Time Frame
at 7 days
Title
Presence of Radiographic Infarcts
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
Time Frame
up to 10 days
Title
Total Infarct Volume
Description
Total infarct volume measured on day 7 dwMRI.
Time Frame
Day 7
Title
Decline in Overall Neurocognition
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.
Time Frame
baseline and 90 days
Title
Decline in Neurocognitive Function in the Verbal Memory Domain at 90 Days
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.
Time Frame
baseline and 90 days
Title
Decline in Neurocognitive Function in the Visual Memory Domain at 90 Days
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.
Time Frame
baseline and 90 days
Title
Decline in Neurocognitive Function in the Executive Function Domain at 90 Day
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.
Time Frame
baseline and 90 days
Title
Decline in Neurocognitive Function in the Visuospatial/Constructional Praxis Domain at 90 Days
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.
Time Frame
baseline and 90 days
Title
Decline in Neurocognitive Function in the Auditory-Verbal Simple Attention Domain at 90 Days
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.
Time Frame
baseline and 90 days
Title
Decline in Neurocognitive Function in the Visuomotor/Information Processing Speed Domain at 90 Days
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.
Time Frame
baseline and 90 days
Title
Modified Rankin Scale >2 at 90 Days
Description
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.
Time Frame
90 days
Title
Barthel Index <= 80
Description
An overall score has full range from 0 to 100, with higher scores indicating greater independence.
Time Frame
90 days
Title
Number of Participants With Confusion Assessment Method (CAM) Delirium Assessment at 7 Days
Time Frame
7 days
Title
Mortality by 90 Days
Description
Incidence of all-cause mortality
Time Frame
up to 90 days
Title
Length of Stay for Index Hospitalization
Time Frame
up to 90 days
Title
Hospital Readmissions
Description
Rate of hospital readmissions
Time Frame
up to 90 days
Title
Quality of Life - Physical Health Composite
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.
Time Frame
at 90 days
Title
Quality of Life - Mental Health Composite
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.
Time Frame
at 90 days
Title
Number of Participants With Emboli Captured
Description
Assessed by the presence of any debris captured in filter of embolic protection device
Time Frame
day 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Annetine C Gelijns, PhD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Richard Weisel, MD
Organizational Affiliation
Toronto General Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
NIH Heart Center at Suburban Hospital
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03766
Country
United States
Facility Name
Montefiore Einstein Heart Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Mission Hospital
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Baylor Research Institute
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G2B7
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
Montreal Heart Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 1C8
Country
Canada
Facility Name
Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
City
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
30007783
Citation
Crestanello JA. "Not in my brain": The use of embolic protection devices to prevent brain embolization during cardiovascular procedures. J Thorac Cardiovasc Surg. 2018 Dec;156(6):e205-e206. doi: 10.1016/j.jtcvs.2018.05.114. Epub 2018 Jun 23. No abstract available.
Results Reference
derived
PubMed Identifier
28787505
Citation
Mack MJ, Acker MA, Gelijns AC, Overbey JR, Parides MK, Browndyke JN, Groh MA, Moskowitz AJ, Jeffries NO, Ailawadi G, Thourani VH, Moquete EG, Iribarne A, Voisine P, Perrault LP, Bowdish ME, Bilello M, Davatzikos C, Mangusan RF, Winkle RA, Smith PK, Michler RE, Miller MA, O'Sullivan KL, Taddei-Peters WC, Rose EA, Weisel RD, Furie KL, Bagiella E, Moy CS, O'Gara PT, Messe SR; Cardiothoracic Surgical Trials Network (CTSN). Effect of Cerebral Embolic Protection Devices on CNS Infarction in Surgical Aortic Valve Replacement: A Randomized Clinical Trial. JAMA. 2017 Aug 8;318(6):536-547. doi: 10.1001/jama.2017.9479.
Results Reference
derived
Learn more about this trial
Neuroprotection in Patients Undergoing Aortic Valve Replacement
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