Neuroprotection in Patients Undergoing Aortic Valve Replacement

Stroke Clinical Trial

Official title:

Neuroprotection In Patients Undergoing Aortic Valve Replacement

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02389894
• Other study ID #: GCO 08-1078-0009
• Secondary ID: 2U01HL088942-07
• Status: Completed
• Phase: N/A
• Start date: March 2015
• Est. completion date: January 2017

Study information

• Verified date: April 2019
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 383
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis
• Brain Infarction
• Cerebrovascular Accident
• Infarction
• Stroke

Intervention

Device:
• Embol-X Embolic Protection Device
per the manufacturer's instructions for use (IFU).
• CardioGard Cannula
CardioGard Cannula, per the manufacturer's instructions for use (IFU).

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Institut Universitaire de Cardiologie de Quebec (Hopital Laval)	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
United States	Mission Hospital	Asheville	North Carolina
United States	Emory University	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	NIH Heart Center at Suburban Hospital	Bethesda	Maryland
United States	Montefiore Einstein Heart Center	Bronx	New York
United States	University of Virginia	Charlottesville	Virginia
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Duke University	Durham	North Carolina
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Southern California	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Baylor Research Institute	Plano	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

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