Neuroprotection in Patients Undergoing Aortic Valve Replacement

Neuroprotection In Patients Undergoing Aortic Valve Replacement

To evaluate the efficacy and safety of embolic protection devices to reduce ischemic brain injury in patients undergoing surgical aortic valve replacement (AVR).

Study Overview

• Status: Completed
• Conditions: Stroke; Aortic Stenosis; Brain Infarction; Cerebrovascular Accident
• Intervention / Treatment: Device: Embol-X Embolic Protection Device; Device: CardioGard Cannula

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: Interventional
• Enrollment (Actual): 383
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
  • Alberta
    • Edmonton, Alberta, Canada, t6g2b7
      • University of Alberta Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Bethesda, Maryland, United States, 20814
      • NIH Heart Center at Suburban Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Einstein Heart Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Plano, Texas, United States, 75093
      • Baylor Research Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Device: Embol-X Embolic Protection Device; per the manufacturer's instructions for use (IFU).; Other Names: Edwards Embol-X embolic protection device
Active Comparator: CardioGard Cannula; The Cardiogard embolic protection device is a curved tip 24-French aortic perfusion cannula.	Device: CardioGard Cannula; CardioGard Cannula, per the manufacturer's instructions for use (IFU).; Other Names: CardioGard Emboli Protection 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 10 days post procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 30 days
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	at 7 days
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	up to 10 days
Total Infarct Volume	Total infarct volume measured on day 7 dwMRI.	Day 7
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.	baseline and 90 days
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.	baseline and 90 days
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.	baseline and 90 days
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.	baseline and 90 days
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.	baseline and 90 days
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.	baseline and 90 days
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.	baseline and 90 days
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.	90 days
Barthel Index <= 80	An overall score has full range from 0 to 100, with higher scores indicating greater independence.	90 days
Number of Participants With Confusion Assessment Method (CAM) Delirium Assessment at 7 Days		7 days
Mortality by 90 Days	Incidence of all-cause mortality	up to 90 days
Length of Stay for Index Hospitalization		up to 90 days
Hospital Readmissions	Rate of hospital readmissions	up to 90 days
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.	at 90 days
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.	at 90 days
Number of Participants With Emboli Captured	Assessed by the presence of any debris captured in filter of embolic protection device	day 1

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Chair: Richard Weisel, MD, Toronto General Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: March 10, 2015
• First Submitted That Met QC Criteria: March 16, 2015
• First Posted (Estimate): March 17, 2015

Study Record Updates

• Last Update Posted (Actual): April 29, 2019
• Last Update Submitted That Met QC Criteria: April 26, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Stroke; Aortic Valve Replacement; Brain Infarction; Embolic Protection Device; atheroma
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Brain Ischemia; Infarction; Stroke; Aortic Valve Stenosis; Brain Infarction
• Other Study ID Numbers: GCO 08-1078-0009; 2U01HL088942-07 (U.S. NIH Grant/Contract)