CTSN Embolic Protection Trial

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

Detailed Description
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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.

Official Title
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Embolic Protection in Patients Undergoing High-Risk Valve Surgery

Conditions
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Delirium, Ischemic Stroke, Acute Kidney Injury, Heart Valve Disease, Coronary Artery Disease

Intervention / Treatment
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* Device: CardioGard Embolic Protection Cannula
* Device: Standard Aortic Cannula


Participation Criteria
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Eligibility Criteria
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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. 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 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 the planned procedure 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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CardioGard Embolic Protection Cannula<br>In patients assigned to the embolic protection device group, the CardioGard Embolic Protection Cannula is used instead, according to the manufacturer's instructions for use (IFU). | Device: CardioGard Embolic Protection Cannula<br>* The CardioGard embolic protection cannula is a device that combines the function of a standard aortic cannula with an added suction mechanism to capture debris that may result from cardiac surgery. The device is comprised of 2 hollow tubes. The first tube is the standard main forward-flow tube to return oxygenated blood to the patient's aorta. The second tube attached to an existing bypass vent port, is a novel element located posteriorly to the main tube; its function is to facilitate blood and particle suction by directing the blood back to the reservoir of the coronary bypass machine, while the retrieved embolic debris is eliminated through the filter of the venous reservoir.<br>|
| Placebo Comparator: Standard Aortic Cannula<br>In patients assigned to the standard cannula group, standard cannulation techniques are performed using any standard aortic cannula of the surgeon's choice | Device: Standard Aortic Cannula<br>* An aortic cannula is a device that is used routinely during cardiac surgery to return oxygenated blood from the cardiac bypass machine into the patient's aorta.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who experience ischemic stroke and Acute Kidney Injury (AKI) | The combined number of patients who experience clinical ischemic strokes and acute kidney injuries that have occurred within 3 days post-randomization. | within 3 days post-randomization | 
| Number of patients who experience of death and delirium | The combined number of patients who experience death and delirium by 7 days post-randomization (with a blanking period for delirium of days 1 and 2 post-operatively). | by 7 days post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who experience a clinical ischemic stroke | The proportion of patients who experience a clinical ischemic stroke within 3 days will be compared between the two groups (i.e., standard cannula versus the CardioGard device). | within 3 days post-randomization | 
| Proportion of patients who experience a clinical ischemic stroke | The proportion of patients who experience a clinical ischemic stroke within 7 days will be compared between the two groups (i.e., standard cannula versus the CardioGard device). | within 7 days post-randomization | 
| Number of patients with disabling clinical stroke | Number of patients with disabling clinical stroke within 3 days post-randomization | within 3 days post-randomization | 
| Number of patients with disabling clinical stroke | Number of patients with disabling clinical stroke within 7 days post-randomization | within 7 days post-randomization | 
| Neurological outcomes assessed by National Institutes of Health Stroke Scale (NIHSS) | Neurological outcomes are assessed by National Institutes of Health stroke Scale (NIHSS) to compare the treatment outcomes of three types of service delivery models. The NIHSS is an 11-item impairment scale to evaluate neurologic outcome and degree of recovery. Each item is scored between 0 and up to 4, total score ranges 0 (normal function) and a maximum possible score 42, with higher score indicating higher level of impairment. These assessments will be administered by blinded neurology trainees or study coordinators who are certified to administer the assessments. | within 3 days post-randomization | 
| Neurological outcomes assessed by National Institutes of Health Stroke Scale (NIHSS) | Neurological outcomes are assessed by National Institutes of Health stroke Scale (NIHSS) to compare the treatment outcomes of three types of service delivery models. The NIHSS is an 11-item impairment scale to evaluate neurologic outcome and degree of recovery. Each item is scored between 0 and up to 4, total score ranges 0 (normal function) and a maximum possible score 42, with higher score indicating higher level of impairment. These assessments will be administered by blinded neurology trainees or study coordinators who are certified to administer the assessments. | within 7 days post-randomization | 
| Number of patients with disabling clinical stroke determined by modified Rankin Scale (mRS) score ≥2 | Number of patients with disabling clinical stroke as indicated by mRS score ≥2. mRS will be assessed at baseline days. The scale runs from 0-6, running from perfect health without symptoms to death. A higher score indicates greater impairment. 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. 3. - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to walk and attend own bodily needs without assistance. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead. | at baseline | 
| Number of patients with disabling clinical stroke determined by modified Rankin Scale (mRS) score ≥2 | Number of patients with disabling clinical stroke as indicated by mRS score ≥2. mRS will be assessed at 30 days. The scale runs from 0-6, running from perfect health without symptoms to death. A higher score indicates greater impairment. 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. 3. - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to walk and attend own bodily needs without assistance. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead. | at 30 days | 
| Number of patients with disabling clinical stroke determined by modified Rankin Scale (mRS) score ≥2 | Number of patients with disabling clinical stroke as indicated by mRS score ≥2. mRS will be assessed at 90 days. The scale runs from 0-6, running from perfect health without symptoms to death. A higher score indicates greater impairment. 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. 3. - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to walk and attend own bodily needs without assistance. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead. | at 90 days | 
| Montreal Cognitive Assessment (MoCA) Score | Global cognitive screening performance will be compared between groups and collected via the Montreal Cognitive Assessment (MoCA) - blind version at presurgical baseline. The MoCA scale is used for detecting cognitive impairment. The scores range between 0 to 30 points; a score of 26 or above was considered normal. Higher values represent a better outcome. | at baseline | 
| Montreal Cognitive Assessment (MoCA) Score | Global cognitive screening performance will be compared between groups and collected via the Montreal Cognitive Assessment (MoCA) - blind version at 90 days. The MoCA scale is used for detecting cognitive impairment. The scores range between 0 to 30 points; a score of 26 or above is considered normal. Higher values represent a better outcome. | at 90 days | 
| Montreal Cognitive Assessment (MoCA) Score | Global cognitive screening performance will be compared between groups and collected via the Montreal Cognitive Assessment (MoCA) - blind version at 12 months. The MoCA scale is used for detecting cognitive impairment. The scores range between 0 to 30 points; a score of 26 or above is considered normal. Higher values represent a better outcome. | at 12 months | 
| Hopkins Verbal Learning Test-Revised (HVLT-R) (verbal learning and memory) Score | HVLT-R is a structured word-list memory test that contains 12 nouns that are read to a participant for three consecutive trials. After each trial, a participant is asked to recall the words that were read to them. The number of words recalled on each trial is summed together to produce a total score for immediate recall and learning. Participants are also asked to recall learned word-list items after a 20-minute delay, yielding a delayed recall score. Participants also perform a subsequent recognition task where they affirm or deny recognition of the word-list materials (from a larger group of 12 target and 12 foil words), the results of which provide a score for recognition discriminability (i.e., target hits - foil misses). The scores for all of these HVLT-R variables are converted to standardized T scores using normative data. The possible T score for each participant ranges from 20 to 80, with higher scores indicative of a better outcome | at baseline | 
| Hopkins Verbal Learning Test-Revised (verbal learning and memory) Score | Hopkins Verbal Learning Test-Revised (HVLT-R) is a structured word-list memory test that contains 12 nouns that are read to a participant for three consecutive trials. After each trial, a participant is asked to recall the words that were read to them. The number of words recalled on each trial is summed together to produce a total score for immediate recall and learning. Participants are also asked to recall learned word-list items after a 20-minute delay, yielding a delayed recall score. Participants also perform a subsequent recognition task where they affirm or deny recognition of the word-list materials (from a larger group of 12 target and 12 foil words), the results of which provide a score for recognition discriminability (i.e., target hits - foil misses). The scores for all of these HVLT-R variables are converted to standardized T scores using normative data. The possible T score for each participant ranges from 20 to 80, with higher scores indicative of a better outcome. | at 90 days post-randomization | 
| Hopkins Verbal Learning Test-Revised (verbal learning and memory) Score | Hopkins Verbal Learning Test-Revised (HVLT-R) is a structured word-list memory test that contains 12 nouns that are read to a participant for three consecutive trials. After each trial, a participant is asked to recall the words that were read to them. The number of words recalled on each trial is summed together to produce a total score for immediate recall and learning. Participants are also asked to recall learned word-list items after a 20-minute delay, yielding a delayed recall score. Participants also perform a subsequent recognition task where they affirm or deny recognition of the word-list materials (from a larger group of 12 target and 12 foil words), the results of which provide a score for recognition discriminability (i.e., target hits - foil misses). The scores for all of these HVLT-R variables are converted to standardized T scores using normative data. The possible T score for each participant ranges from 20 to 80, with higher scores indicative of a better outcome. | at 12 months post-randomization | 
| Brief Visuospatial Memory Test - Revised (visual learning & memory and constructional praxis) | Analogous to the HVLT-R, the Brief Visuospatial Memory Test (BVMT-R) assesses visual learning and memory by measuring how well individuals can recall a page of six line drawings presented visually for 10 seconds over three repetition trials. Examinee totals from the three repetition trials is taken as a measure of visual short-term learning and memory, and after a 20-minute delay, examinees are asked to reproduce as many as possible of the previously presented line drawings (assessing long-term visual memory retention and recall). Examinees are then shown 12 line drawings, six of which were the line drawings they were asked to reproduce earlier and six new drawings, and examinees are asked if they recognize the line drawings as ones they have seen before (assessing long-term visual recognition memory). Raw scores are converted to T-scores, normed by age and sex. A higher T-score representing a better outcome. | at 90 days post-procedure | 
| Oral Trail Making Test - Parts A and B (executive function) | The Trail Making Test consists of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1 - 13) and letters (A - L); as in Part A, the patient draws lines to connect the circles in an ascending pattern, but with the added task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). The patient should be instructed to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Time the patient connects the trail. If the patient makes an error, point it out immediately and allow the patient to correct it. Results for part B are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment. | at baseline | 
| Oral Trail Making Test - Parts A and B (executive function) | The Trail Making Test consists of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1 - 13) and letters (A - L); as in Part A, the patient draws lines to connect the circles in an ascending pattern, but with the added task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). The patient should be instructed to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Time the patient connects the trail. If the patient makes an error, point it out immediately and allow the patient to correct it. Results for part B are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment. | at 90 days post-randomization | 
| Oral Trail Making Test - Parts A and B (executive function) | The trail Making Test consist of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1 - 13) and letters (A - L); as in Part A, the patient draws lines to connect the circles in an ascending pattern, but with the added task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). The patient should be instructed to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Time the patient connects the trail. If the patient makes an error, point it out immediately and allow the patient to correct it. Results for part B are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment. | at 12 months post-randomization | 
| Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span (auditory-verbal attention) | The WAIS-R Digit Span test assesses short term or working memory. The examinee listens to sequences of numbers orally and then repeats them as heard, in increasing order, and in reverse order. The raw scores for digit span range from a minimum of 2 to a maximum of 8. For this test, the longer the span the better the cognition; therefore, the higher score is the better outcome. | baseline | 
| Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span (auditory-verbal attention) | The WAIS-R Digit Span test assesses short term or working memory. The examinee listens to sequences of numbers orally and then repeats them as heard, in increasing order, and in reverse order. The raw scores for digit span range from a minimum of 2 to a maximum of 8. For this test, the longer the span the better the cognition; therefore, the higher score is the better outcome. | at 90 days post-randomization | 
| Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span (auditory-verbal attention) | The WAIS-R Digit Span test assesses short term or working memory. The examinee listens to sequences of numbers orally and then repeats them as heard, in increasing order, and in reverse order. The raw scores for digit span range from a minimum of 2 to a maximum of 8. For this test, the longer the span the better the cognition; therefore, the higher score is the better outcome. | at 12 months post-randomization | 
| Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol Substitution Test (processing speed) | The WAIS-R Digit Symbol Substitution Test (DSST) is a paper-and-pencil cognitive test that consist of number-symbol pairs. It requires the examinee to copy, into spaces below rows of numbers, the symbols that are paired to each number. The DSST score is the number of digits coded correctly in a 90-second test period | at baseline | 
| Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test (verbal fluency/executive function) | The D-KEFS Verbal Fluency Test is comprised of three testing conditions: Letter Fluency, Category Fluency, and Category Switching. This test measures multiple aspects of verbal productivity and cognitive flexibility. It evaluates effectiveness of novel and semantic search strategies, and assesses flexibility in the implementation of word search strategies. There are three conditions in the test in which the examinee must say as many words as they can by letter, category, and category switching prompts. | at baseline | 
| Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test (verbal fluency/executive function) | The D-KEFS Verbal Fluency Test is comprised of three testing conditions: Letter Fluency, Category Fluency, and Category Switching. This test measures multiple aspects of verbal productivity and cognitive flexibility. It evaluates effectiveness of novel and semantic search strategies, and assesses flexibility in the implementation of word search strategies. There are three conditions in the test in which the examinee must say as many words as they can by letter, category, and category switching prompts. | at 90 days post-randomization | 
| Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test (verbal fluency/executive function) | The D-KEFS Verbal Fluency Test is comprised of three testing conditions: Letter Fluency, Category Fluency, and Category Switching. This test measures multiple aspects of verbal productivity and cognitive flexibility. It evaluates effectiveness of novel and semantic search strategies, and assesses flexibility in the implementation of word search strategies. There are three conditions in the test in which the examinee must say as many words as they can by letter, category, and category switching prompts. | at 12 months post-randomization | 
| Incidence of Delirium | The incidence of delirium will be assessed daily by the Confusion Assessment Method (3D-CAM or CAM-ICU for intubated patients) during the first 7 days post-randomization. The CAM consists of 4 features: 1-Onset, 2-Inattention, 3-Disorganized thinking, and 4-altered level of consciousness. The diagnosis of delirium by CAM is based on the presence of features 1 and 2, and either 3 or 4 and involves the presence/absence of delirium, but not its severity. Any error or behavioral observation consistent with a delirium feature means that feature is present. | first 7 days post-randomization | 
| Duration of Delirium | The duration of delirium will be measured as the number of days with positive CAM assessments by 7 days post-randomization. The CAM consists of 4 features: 1-Onset, 2-Inattention, 3-Disorganized thinking, and 4-altered level of consciousness. The diagnosis of delirium by CAM is based on the presence of features 1 and 2, and either 3 or 4. | first 7 days post-randomization | 
| Severity of Delirium | The severity of delirium will be measured during daily screening using standardized algorithms for extracting symptom severity from the 3D-CAM and CAM-ICU. | first 7 days post-randomization | 
| Number of Patients who experience Acute kidney injury (AKI) | Number of Patients who experience Acute kidney injury will be assessed within 7 days post-randomization. | within -7 days post-randomization | 
| All-cause mortality | All-cause mortality within 90 days post-randomization will be assessed. | within 90 days post-randomization | 
| All-cause mortality | All-cause mortality within 12-months post-randomization will be assessed. | within 12 months post-randomization | 
| Length of Index Hospitalization | Overall length of stay for the index hospitalization post-randomization will be measured and broken down by days spent in the ICU versus days not in the ICU. | at hospital discharge, up to 30 days | 
| Discharge disposition | Discharge disposition | at hospital discharge, up to 30 days | 
| Readmissions rates | Readmission rates will be calculated for the first 90 days following randomization. Hospitalizations will be classified for all causes including for cardiovascular readmissions. | first 90 days | 
| Readmissions rates | Readmission rates will be calculated for the duration of follow-up, out to 1 year. Hospitalizations will be classified for all causes including for cardiovascular readmissions. | up to 1 year post-randomization | 
| Days Alive out of Hospital | Days alive out of hospital and nursing/rehab facilities within 90 days after randomization | within 90 days post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Embolic Protection, Cardiac Surgery, CardioGard