EDWARDS INTUITY Valve System CADENCE Study

Study Overview
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Brief Summary
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The study purpose is to compare the EDWARDS INTUITY valve system with commercially available stented aortic bioprostheses, in patients requiring aortic valve replacement surgery with coronary artery bypass.

Detailed Description
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This is a randomized study comparing the cross-clamp time (XCT) and cardiopulmonary bypass time (CPBT) of the EDWARDS INTUITY valve system with any commercially available stented aortic bioprosthesis, in patients with logistic EuroSCORE 1 ≥ 6 undergoing elective surgical aortic valve replacement surgery with concomitant coronary bypass grafts. Additionally, the aim is to gather sufficient data to quantify the effect size of short term patient benefit outcomes previously identified from literature and finally to explore additional healthcare resource utilization or health economic endpoints.

Official Title
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A Randomized Comparison of the EDWARDS INTUITY Valve System anD commErcially Available Aortic Bioprostheses in Subjects uNdergoing surgiCal Aortic Valve replacEment

Conditions
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Aortic Valve Disease, Aortic Stenosis

Intervention / Treatment
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* Device: EDWARDS INTUITY
* Device: Stented aortic bioprostheses


Participation Criteria
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Eligibility Criteria
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Inclusion: ≥18 years of age aortic stenosis / mixed aortic stenosis and aortic insufficiency SAVR+CABG (1-4 distal anastomoses) Log. EuroSCORE ≥6 NYHA Class ≥II Exclusion (i.a.): pure aortic insufficiency pre-existing prosthetic heart valve or ring congenital true bicuspid / unicuspid aortic valve LVEF <20%

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EDWARDS INTUITY<br>EDWARDS INTUITY Valve System, Model 8300A | Device: EDWARDS INTUITY<br>* To evaluate cardiac performance characteristics and adverse events rates associated with the EDWARDS INTUITY Valve in patients undergoing AVR & CABG.<br>* Other names: aortic valve replacement;|
| Active Comparator: Stented aortic bioprostheses<br>Stented aortic bioprostheses | Device: Stented aortic bioprostheses<br>* In comparison to control valves available on the market.<br>* Other names: aortic valve replacement;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Subject Time Spent on Cardiopulmonary Cross Clamp | Cardiopulmonary cross clamp time is the amount of time that the patient's aorta (blood vessel) is clamped by a surgical instrument used in cardiac surgery. This allows the normal blood flow to be sent to an artificial heart and lung machine to keep it at a constant temperature and oxygen level. | At time of surgery, an average of 1.5 hours | 
| Average Amount of Time Subject Spent on Cardiopulmonary Bypass | Cardiopulmonary bypass time is the amount of time that the patient's blood circulates through an artificial heart and lung machine during cardiac surgery. | At time of surgery, an average of 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Change From Baseline in New York Heart Association (NYHA) Class at 2 Years. | The New York Heart Association (NYHA) functional classification system relates symptoms to everyday activities and the patient's quality of life. Class I. Patients with cardiac disease but without resulting limitation of physical activity. Class II. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Class III. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Class IV. Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. | Baseline and 2 Years | 
| Subject's Average Mean Gradients (mmHg) Measurements Over Time. | Mean gradient is the average flow of blood through the aortic valve measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. Mean gradient values depend on the size and type of valve. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subject's Average Peak Gradients (mmHg) Measurements Over Time. | Peak gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. | 30 days, 3 months, 6 months, 1 year, 2 year | 
| Subject's Effective Orifice Area (EOA) Measurement Over Time. | Effective orifice area represents the cross-sectional area of the blood flow downstream of the aortic valve. Effective orifice area is evaluated by echocardiography over time. | 30 days, 3 months, 6 months, 1 year, 2 year | 
| Subject's Effective Orifice Area Index (EOAI) Measurement Over Time. | Effective orifice area index represents the minimal cross-sectional area of the blood flow downstream of the aortic valve divided by the person's body surface area. Effective orifice area index is evaluated by echocardiography over time. | 30 days, 3 months, 6 months, 1 year, 2 year | 
| Amount of Aortic Valvular Regurgitation Over Time. | Aortic valvular regurgitation occurs when the aortic valve in the heart does not close tightly allowing some of the blood that was pumped out of the heart to leak back into it. Aortic valvular regurgitation is evaluated by echocardiography over time. It is assessed on a scale from 0 to 4, where 0 represents no regurgitation and 4 represents severe regurgitation. | 30 days, 3 months, 6 months, 1 year, 2 year | 
| Conversion of Edwards INTUITY Surgical Aortic Valve to Control During Surgery. | Subjects randomized to the Edwards INTUITY group that were converted to the control group and received commercially available surgical aortic heart valves during surgery. | Prior to Surgery | 
| Subjects Who Required a Thoracic Resternotomy Over Time | Number of Subjects who had a surgical opening of their chest after their initial aortic heart valve surgery shown over various time points. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects Who Received a Permanent Pacemaker Over Time. | Number of Subjects who received a Permanent Pacemaker shown over various time points. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects With a Major Paravalvular Leak (OPC) Over Time | Number of subjects who experienced a Major Paravalvular Leak (OPC) shown over various time points. Paravalvular leak refers to blood flowing through a channel between the implanted artificial valve and the cardiac tissue as a result of inappropriate sealing. Paravalvular leak is evaluated by echocardiography over time. It is assessed on a scale from 0 to 4, where 0 = no leak, 1 = a trace leak, 2 = a mild leak, 3 = a moderate leak, and 4 = a severe leak. A major paravalvular leak (OPC)are any events of leak that required surgical intervention or were considered an serious adverse event. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects Who Experienced Major Bleeding Over Time. | Number of subjects who experienced Major Bleeding shown over various time points. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects Who Experienced Respiratory Failure Over Time | Number of subjects who experienced a Respiratory Failure shown over various time points. Respiratory failure happens when not enough oxygen passes from your lungs to your blood. | 30 days, 3 Months , 6 Months, 1 Year, 2 Years. | 
| Subjects With a Cerebral Vascular Accident or Permanent Stroke Over Time | Number of subjects who experienced a Cerebral Vascular Accident or Permanent Stroke shown over various time points. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects With Renal Failure Over Time | Number of subjects who experienced Renal (kidney) Failure shown over various time points. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects With Endocarditis Over Time | Number of subjects who experienced Endocarditis shown over various time points. Endocarditis is an infection of the endocardium, which is the inner lining of your heart chambers and heart valves. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects With a Deep Sternal Would Infection Over Time | Number of subjects who experienced a Deep Sternal Wound Infection shown over various time points. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects With a Myocardial Infarction Over Time | Number of subjects who experienced a Myocardial Infarction shown over various time points. A Myocardial infarction, commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects With a Thromboembolism Over Time | Number of subjects who experienced a Thromboembolism shown over various time points. A thromboembolism is an obstruction of a blood vessel by a blood clot that has become dislodged from another site in the circulation. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects With a Cardiac Tamponade Over Time | Number of subjects who experienced a Cardiac Tamponade shown over various time points. Cardiac tamponade is when fluid in the pericardium (the sac around the heart) builds up and results in compression (squeezing) of the heart. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects With a Cardiac Reoperation for Any Reason Over Time | Number of subjects who experienced a Cardiac reoperation for any reason shown over various time points. | 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subjects Who Died Intraoperatively | Number of subjects who died during surgery. | Surgery | 
| Subject's Average Score on the EQ-5D- Quality of Life Questionnaire Over Time | The EQ-5D is a standardized questionnaire that asks subjects to rate themselves (no problems, some problems, extreme problems) on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The scale is indexed and ranges from a minimum of 0.275 and a maximum of 1.000. A lower number indicates the participants experiences more problems and a higher number indicates the participants experiences fewer problems. | Baseline, 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subject's Average Score SF-12 - Quality of Life Questionnaire Over Time | The Medical Outcomes Study Short-Form 12 (SF-12) - Physical Component Summary (PCS) and Mental Component Summary (MCS). The SF-12 questionnaire scale ranges from 100, which reflects the best health status to 0, which reflects the worse health status. Subject's Average Score at Baseline and at each follow-up interval until 2 year - SF-12. | Baseline, 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Subject's Average Score on the KCCQ - Quality of Life Questionnaire Over Time | The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores range from 0-100, in which higher scores reflect better health status. Subjects took this questionnaire at baseline, 30 days, 3 Months, 6 Months, 1 Year, and 2 Years. | Baseline, 30 days, 3 Months, 6 Months, 1 Year, 2 Years. | 
| Health Care Utilization | The average amount of time the subjects spent in the intensive care unit, the intermediate care length of stay, and the average total length of hospital stay after their heart valve replacement procedure. | Day of surgical procedure through discharge from the hospital, an average of 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic Valve Replacement, Aortic Stenosis, EDWARDS INTUITY