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Neuroprotection in Patients Undergoing Aortic Valve Replacement

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02389894
Recruitment Status : Completed
First Posted : March 17, 2015
Results First Posted : April 29, 2019
Last Update Posted : April 29, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Annetine Gelijns, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE March 10, 2015
First Posted Date  ICMJE March 17, 2015
Results First Submitted Date  ICMJE December 12, 2017
Results First Posted Date  ICMJE April 29, 2019
Last Update Posted Date April 29, 2019
Study Start Date  ICMJE March 2015
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2019)
Percentage of Participants With Freedom From Clinical or Radiographic Central Nervous System (CNS) Infarction [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 16, 2015)
freedom from clinical or radiographic CNS infarction [ Time Frame: 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 DWI at 7 (± 3) days post procedure for presence of brain lesions and to measure the number and volume of any present lesions.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2019)
  • Number of Participants With a Composite Endpoint of Mortality, Clinical Stroke, and Acute Kidney Injury [ Time Frame: 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 [ Time Frame: at 7 days ]
    The number of patients who experience a clinically apparent stroke by 7 days post-op
  • Presence of Radiographic Infarcts [ Time Frame: 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
  • Total Infarct Volume [ Time Frame: Day 7 ]
    Total infarct volume measured on day 7 dwMRI.
  • Decline in Overall Neurocognition [ Time Frame: 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.
  • Decline in Neurocognitive Function in the Verbal Memory Domain at 90 Days [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Visuospatial/Constructional Praxis Domain at 90 Days [ Time Frame: 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.
  • Decline in Neurocognitive Function in the Auditory-Verbal Simple Attention Domain at 90 Days [ Time Frame: 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 [ Time Frame: 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.
  • Modified Rankin Scale >2 at 90 Days [ Time Frame: 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.
  • Barthel Index <= 80 [ Time Frame: 90 days ]
    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 [ Time Frame: 7 days ]
  • Mortality by 90 Days [ Time Frame: up to 90 days ]
    Incidence of all-cause mortality
  • Length of Stay for Index Hospitalization [ Time Frame: up to 90 days ]
  • Hospital Readmissions [ Time Frame: up to 90 days ]
    Rate of hospital readmissions
  • Quality of Life - Physical Health Composite [ Time Frame: 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.
  • Quality of Life - Mental Health Composite [ Time Frame: 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.
  • Number of Participants With Emboli Captured [ Time Frame: day 1 ]
    Assessed by the presence of any debris captured in filter of embolic protection device
Original Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2015)
  • A composite endpoint of mortality, clinical stroke, and acute kidney injury [ Time Frame: up to 30 days ]
    The proportion of patients who have had a clinical ischemic stroke, acute kidney injury (AKI), or death within 30 days of surgery.
  • Clinical and Radiographic Brain Injury [ Time Frame: up to 90 days ]
    The proportion of patients who experience a non-silent stroke. The volume and number of brain lesions will be measured using 1.5 T DWI.
  • Safety of study device, as measured by Incidence of serious or protocol defined adverse events. [ Time Frame: up to 90 days ]
    Incidence of serious or protocol defined adverse events.
  • Emboli Volume [ Time Frame: Day 1 ]
    Volume of the emboli captured by the Embol-X filter will be processed using electron microscopy (EM)
  • Change in Hopkins Verbal Learning Test [ Time Frame: baseline and 90 days ]
    Change in neurocognitive function at 90 days as compared to baseline
  • Change in Trailmaking Tests A and B [ Time Frame: baseline and 90 days ]
    Change in neurocognitive function at 90 days as compared to baseline
  • Change in MCG Complex Figures [ Time Frame: baseline and 90 days ]
    Change in neurocognitive function at 90 days as compared to baseline
  • Change in Digit Span [ Time Frame: baseline and 90 days ]
    Change in neurocognitive function at 90 days as compared to baseline
  • Change in Digit Substitution Test [ Time Frame: baseline and 90 days ]
    Change in neurocognitive function at 90 days as compared to baseline
  • Change in COWA Verbal Fluency Test [ Time Frame: baseline and 90 days ]
    Change in neurocognitive function at 90 days as compared to baseline
  • Change in NIH Stroke Scale [ Time Frame: baseline and 90 days ]
    Neurological outcomes assessed at 90 days as compared to baseline
  • Change in Modified Rankin Scale [ Time Frame: baseline and 90 days ]
    Neurological outcomes assessed at 90 days as compared to baseline
  • Change in Barthel Index [ Time Frame: baseline and 90 days ]
    Neurological outcomes assessed at 90 days as compared to baseline
  • Change in confusion Assessment Method (CAM) Delirium Assessment [ Time Frame: baseline and 90 days ]
    Delirium assessed at 90 days as compared to baseline
  • Survival [ Time Frame: up to 90 days ]
    Incidence of all-cause mortality
  • Length of Stay hospitalization [ Time Frame: up to 90 days ]
  • Hospital Readmissions [ Time Frame: up to 90 days ]
    Incidence of hospital readmissions
  • Mortality [ Time Frame: up to 90 days ]
    Number of days alive out of the hospital
  • Quality of life [ Time Frame: up to 90 days ]
    Assessed by Short Form-12 (SF-12) and Geriatric Depression Scale (GDS) composite
  • Device Performance [ Time Frame: day 1 ]
    Assessed by need for additional surgery or re-intervention related to use of the embolic protection device
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neuroprotection in Patients Undergoing Aortic Valve Replacement
Official Title  ICMJE Neuroprotection In Patients Undergoing Aortic Valve Replacement
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Aortic Stenosis
  • Brain Infarction
  • Cerebrovascular Accident
  • Stroke
Intervention  ICMJE
  • Device: Embol-X Embolic Protection Device
    per the manufacturer's instructions for use (IFU).
    Other Name: Edwards Embol-X embolic protection device
  • Device: CardioGard Cannula
    CardioGard Cannula, per the manufacturer's instructions for use (IFU).
    Other Name: CardioGard Emboli Protection Cannula
Study Arms  ICMJE
  • Active Comparator: 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.
    Intervention: Device: Embol-X Embolic Protection Device
  • Active Comparator: CardioGard Cannula
    The Cardiogard embolic protection device is a curved tip 24-French aortic perfusion cannula.
    Intervention: Device: CardioGard Cannula
  • No Intervention: Standard Cannula
    Patients in this arm will receive the standard of care surgical procedure using a cannula of the surgeon's choosing.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 12, 2017)
383
Original Estimated Enrollment  ICMJE
 (submitted: March 16, 2015)
330
Actual Study Completion Date  ICMJE January 2017
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02389894
Other Study ID Numbers  ICMJE GCO 08-1078-0009
2U01HL088942-07 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Annetine Gelijns, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Icahn School of Medicine at Mount Sinai
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Annetine C Gelijns, PhD Icahn School of Medicine at Mount Sinai
Study Chair: Richard Weisel, MD Toronto General Hospital
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP