Clinical Trial: Neuroprotection in Patients Undergoing Aortic Valve Replacement

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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 Summary: 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.
Sponsor: Icahn School of Medicine at Mount Sinai

Current Primary Outcome: 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: 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.


Current Secondary Outcome:

  • 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 (3.0 T is acceptable if 1.5 T not available).
  • 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


Original Secondary Outcome:

  • 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


Information By: Icahn School of Medicine at Mount Sinai

Dates:
Date Received: March 10, 2015
Date Started: March 2015
Date Completion:
Last Updated: April 12, 2017
Last Verified: April 2017