Clinical trial NCT06027788: CTSN Embolic Protection Trial
Official title: Embolic Protection in Patients Undergoing High-Risk Valve Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Delirium
Ischemic Stroke
Acute Kidney Injury
Heart Valve Disease
Coronary Artery Disease
Keywords: Embolic Protection
Cardiac Surgery
CardioGard
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-09-07
Enrollment: 842
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized 1:1 to the embolic protection device or to a standard cannula in the OR immediately after sternotomy and confirmation by the surgical team of the patient's suitability for the proposed intervention (CardioGard embolic protection device).
Primary purpose: PREVENTION

Brief summary: This is a prospective, multi-center, randomized effectiveness trial of the CardioGard Embolic Protection Cannula in high-risk valve surgery patients.

Detailed description: This is a prospective, multicenter, randomized controlled clinical trial that will evaluate the effectiveness and safety of the CardioGard embolic protection cannula compared to a standard cannula. The enrollment period is expected to last 30 months, and all patients will be followed for 12 months post procedure.

RANDOMIZATION Patients will be randomized 1:1 to the embolic protection device or to a standard cannula in the operating room (OR) immediately after sternotomy and confirmation by the surgical team of the patient's suitability for the proposed intervention (CardioGard embolic protection device). Randomization will be with equal allocation and stratified by site and by procedure (i.e., isolated valve surgery or combined procedures, such as double valve or valve plus coronary artery bypass grafting, CABG). The randomization assignment will be controlled centrally and performed through a web-based data collection system that automates the delivery of the randomization codes. From the point of treatment assignment, primary efficacy will be analyzed by intention-to-treat; that is, the patients will be grouped by their assignments at randomization regardless of whether or not they actually received the treatment to which they were assigned.

STUDY POPULATION The patient population for this trial consists of patients age ≥ 60 undergoing different types of valve surgery with or without CABG via full or minimal-access sternotomy using legally marketed valve(s). Specific inclusion and exclusion criteria are listed below. All patients who meet the eligibility criteria may be included in the study regardless of gender, race, or ethnicity.

SUBSTUDY Sleep Disturbance Ancillary Sub-Study - Patients undergoing surgery for valvular heart disease (VHD) are at high risk for adverse events, including high rates of post-operative delirium (POD). Should circadian disruption be found to be an important predictor in this high-risk population, safe, low cost, and easy to administer therapies to regulate circadian rhythm such as light therapy could be evaluated in future studies

The aims of this ancillary sub-study include:

1. To investigate the association between short sleep duration, less sleep regularity, and greater circadian rhythm disruption prior to surgery and POD within 7 days of VHD surgery.
2. To investigate the association between short sleep duration, less sleep regularity and greater circadian rhythm disruption (reduced melatonin and cortisol amplitudes) after surgery and POD within 7 days of VHD surgery.

Approximately 300 EMPRO trial participants will be enrolled into the ancillary study. The study is being conducted in highly experienced clinical centers in the U.S. and Canada. The estimated enrollment period is 12-15 months.

All eligible and consented patients in the parent EMPRO trial will be offered enrollment in this ancillary study through the parent trial consent process.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 60 years
* Planned de novo or redo:

  * Surgical aortic valve replacement SAVR ± ascending aortic repair (if circulatory arrest is not required) ± CABG
  * Mitral valve replacement (MVR) ± CABG
  * Mitral Valve Repair + CABG,
  * Double/Triple valve surgery ± CABG; Ross procedure These procedures can be done via a full or minimal-access sternotomy (using central aortic perfusion cannulae) with legally marketed valve(s), and can be done in combination with an left atrial appendage (LAA) closure/excision or partial/complete Maze procedure.
  * Valve sparing aortic root replacement (David procedure)
  * Valve sparing aortic root replacement (David procedure)
* No evidence of neurological impairment as defined by a NIHSS ≤1 and modified Rankin scale (mRS) ≤2 within 30 days prior to randomization
* Ability to provide informed consent and comply with the protocol

Exclusion Criteria:

* History of clinical stroke within 3 months prior to randomization
* Cerebral and or aortic arch arteriography or interventions within 3 days of the planned procedure
* Coronary catheterization within 3 days of index procedure, and the required repeat NIHSS score post-catheterization is worse than the screening/baseline NIHSS score conducted prior to the catheterization
* Active endocarditis at time of randomization with vegetation criteria
* Clinical signs of cardiogenic shock or treatment with IV inotropic therapy prior to randomization
* Participation in an interventional (drug or device) trial
* Isolated mitral valve repair, isolated tricuspid valve repair or combined mitral valve repair and tricuspid valve repair
* Anticipated requirement for prolonged mechanical ventilation greater than 48 hours after surgery in the opinion of the investigator
* Planned concomitant carotid endarterectomy during index surgical procedure

Primary outcomes:
measure: Number of patients who experience ischemic stroke and Acute Kidney Injury (AKI)
timeFrame: within 3 days post-randomization
measure: Number of patients who experience of death and delirium
timeFrame: by 7 days post-randomization
Secondary outcomes:
measure: Proportion of patients who experience a clinical ischemic stroke
timeFrame: within 3 days post-randomization
measure: Proportion of patients who experience a clinical ischemic stroke
timeFrame: within 7 days post-randomization
measure: Number of patients with disabling clinical stroke
timeFrame: within 3 days post-randomization
measure: Number of patients with disabling clinical stroke
timeFrame: within 7 days post-randomization
measure: Neurological outcomes assessed by National Institutes of Health Stroke Scale (NIHSS)
timeFrame: within 3 days post-randomization
measure: Neurological outcomes assessed by National Institutes of Health Stroke Scale (NIHSS)
timeFrame: within 7 days post-randomization
measure: Number of patients with disabling clinical stroke determined by modified Rankin Scale (mRS) score ≥2
timeFrame: at baseline
measure: Number of patients with disabling clinical stroke determined by modified Rankin Scale (mRS) score ≥2
timeFrame: at 30 days
measure: Number of patients with disabling clinical stroke determined by modified Rankin Scale (mRS) score ≥2
timeFrame: at 90 days
measure: Montreal Cognitive Assessment (MoCA) Score
timeFrame: at baseline
measure: Montreal Cognitive Assessment (MoCA) Score
timeFrame: at 90 days
measure: Montreal Cognitive Assessment (MoCA) Score
timeFrame: at 12 months
measure: Oral Trail Making Test - Parts A and B (executive function)
timeFrame: at baseline
measure: Oral Trail Making Test - Parts A and B (executive function)
timeFrame: at 90 days post-randomization
measure: Oral Trail Making Test - Parts A and B (executive function)
timeFrame: at 12 months post-randomization
measure: Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span (auditory-verbal attention)
timeFrame: baseline
measure: Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span (auditory-verbal attention)
timeFrame: at 90 days post-randomization
measure: Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span (auditory-verbal attention)
timeFrame: at 12 months post-randomization
measure: Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol Substitution Test (processing speed)
timeFrame: at baseline
measure: Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test (verbal fluency/executive function)
timeFrame: at baseline
measure: Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test (verbal fluency/executive function)
timeFrame: at 90 days post-randomization
measure: Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test (verbal fluency/executive function)
timeFrame: at 12 months post-randomization
measure: Incidence of Delirium
timeFrame: first 7 days post-randomization
measure: Duration of Delirium
timeFrame: first 7 days post-randomization
measure: Severity of Delirium
timeFrame: first 7 days post-randomization
measure: Number of Patients who experience Acute kidney injury (AKI)
timeFrame: within -7 days post-randomization
measure: All-cause mortality
timeFrame: within 90 days post-randomization
measure: All-cause mortality
timeFrame: within 12 months post-randomization
measure: Length of Index Hospitalization
timeFrame: at hospital discharge, up to 30 days
measure: Discharge disposition
timeFrame: at hospital discharge, up to 30 days
measure: Readmissions rates
timeFrame: first 90 days
measure: Readmissions rates
timeFrame: up to 1 year post-randomization
measure: Days Alive out of Hospital
timeFrame: within 90 days post-randomization
measure: Actigraphy
timeFrame: 7-day period prior to index surgical procedure and Day 1 post index surgical procedure through hospital discharge
measure: Amount of Circadian Light
timeFrame: 7-day period prior to index surgical procedure
measure: Photopic Light Levels
timeFrame: 7-day period prior to index surgical procedure
measure: Circadian Stimulus Values
timeFrame: 7-day period prior to index surgical procedure
measure: Richards-Campbell Sleep Questionnaire
timeFrame: Day 1 post index surgical procedure through patient discharge from the ICU (average ICU stay is 3 days)
Other outcomes:
Locations:
city: North Little Rock
country: United States
facility: CHI St. Vincent Heart Institute
state: Arkansas
city: Los Angeles
country: United States
facility: Keck Hospital of the University of Southern California
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Bloomington
country: United States
facility: Indiana University
state: Indiana
city: Fort Wayne
country: United States
facility: Indiana Ohio Heart
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins Medicine
state: Maryland
city: College Park
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian-Cornell Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Hospital Brooklyn
state: New York
city: New York
country: United States
facility: Northwell Health
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Quebec City
country: Canada
facility: Hôpital Laval
state: Quebec
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Annetine C. Gelijns, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Steve Messe, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwell Health
name: Alexander Iribarne, MD
role: PRINCIPAL_INVESTIGATOR
References: