EDWARDS INTUITY Valve System CADENCE-MIS Study

Study Overview
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Brief Summary
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The study purpose is to compare the EDWARDS INTUITY valve system in a minimal invasive surgical approach (MIS) with any commercially available aortic bioprosthesis in standard full sternotomy surgical approach.

Detailed Description
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This is a randomized study to compare the cross-clamp time (XCT) and cardiopulmonary bypass time (CPBT) of the EDWARDS INTUITY valve system in a minimally invasive surgical approach (MIS) with any commercially available aortic bioprosthesis in standard full sternotomy surgical approach, in patients with logistic EuroScore < 20 undergoing elective isolated aortic valve replacement (AVR) surgery. Additionally, the aim is to gather sufficient data to quantify the effect size of short term patient benefit outcomes previously identified from literature and to explore additional healthcare resource utilization 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 Using Minimally InvaSive Techniques

Conditions
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Aortic Valve Disease, Aortic Stenosis

Intervention / Treatment
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* Device: EDWARDS INTUITY Valve System, Model 8300A
* Device: Stented Aortic Bioprostheses


Participation Criteria
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Eligibility Criteria
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Inclusion: adult male or female ≥18 years of age symptomatic for aortic stenosis / mixed aortic stenosis and aortic insufficiency disease for which isolated surgical aortic valve replacement without concomitant procedures is planned EuroSCORE <20 NYHA Class ≥II Subject has signed and dated the investigation informed consent form prior to study specific procedures are performed Subject is geographically stable and agrees to participate in follow-up assessments as specified in the protocol and informed consent Exclusion (i.a.): pure aortic insufficiency previous cardiac surgery (involved FS or MIS approach) congenital true bicuspid / unicuspid aortic valve requires emergency surgery or has had emergency surgery for any reason ≤ 1 month before the intended treatment LVEF <25% active endocarditis ≤ 6 months before the intended treatment acute MI ≤ 90 days before the intended treatment had a stroke or transient ischemic attack within six months prior to scheduled aortic valve replacement surgery oxygen or ventilator dependent life expectancy < 12 months substance abuser Female subject is pregnant or lactating documented leukopenia (WBC < 3.5x 103/μL), acute anemia (Hgb < 10.0 gm/dL or < 6.2 mmol/L), thrombocytopenia (platelet count < 100x 103/mL), or history of bleeding diathesis or coagulopathy hemodynamic or respiratory instability requiring inotropic support, mechanical circulatory support, or mechanical ventilation within 30 days of procedure documented echocardiographic evidence of intracardiac mass, thrombus or vegetation renal insufficiency as determined by Serum creatinine ≥ 200 μmol/L (2.27 mg/dL) at screening or end-stage renal disease requiring chronic dialysis documented hyperparathyroidism currently participating in an investigational drug or device trial for which follow-up has not yet been completed Minimally Invasive access to the heart is not possible due to anatomical constraints or any other pre-existing condition Intra-operative Exclusion: has calcium on the anterior mitral leaflet which cannot be removed has extensive calcification of the aortic root Annular deformation which may or may not be caused by too extensive decalcification of the aortic annulus has left atrial thrombus The position of the coronary ostia relative to the EDWARDS INTUITY Valve would result in obstruction of blood flow hemodynamically unstable during the procedure requiring the procedure to be aborted prior to insertion of the study bioprosthesis and delivery system Study device is not available in the correct size for the subject

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 Valve System, Model 8300A<br>* To evaluate cardiac performance characteristics and adverse events rates associated with the EDWARDS INTUITY Valve in patients undergoing MIS-AVR.<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 undergoing FS-AVR<br>* Other names: aortic valve replacement;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median 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 hour | 
| Median 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 1 hour | 

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. | Baseline, Discharge, 30 days, 3 Months, 1 Year | 
| 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. | Baseline, Discharge, 30 days, 3 Months, 1 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. | Baseline, Discharge, 30 days, 3 Months, 1 Year | 
| Amount of Paravalvular Leak Over Time. | Number of subjects who experienced a Paravalvular Leak 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 minimum of 0 to maximum of 4, where 0 = no leak, 1 = a trace leak, 2 = a mild leak, 3 = a moderate leak, and 4 = a severe leak. Higher numbers on the scale show a worsening outcome. | Discharge, 30 days, 3 month, 1 year | 
| Conversion of Edwards INTUITY Surgical Aortic Valve to Control Surgical Aortic Heart Valves 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, 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, 1 Year, 2 Years. | 
| Subjects With a Paravalvular Leak > or Equal to 3+ and/or Requiring Intervention Over Time | Number of subjects who experienced a Paravalvular Leak 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. Higher numbers on the scale show a worsening outcome. | 30 days, 3 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, 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, 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, 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, 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, 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, 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, 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, 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, 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, 1 Year, 2 Years. | 
| Conversion of Subjects Undergoing Minimally Invasive Surgical Incision to Full Sternotomy for the Randomized to Edwards INTUITY Group During Surgery. | Subjects Randomized to Edwards INTUITY Group's Surgical Aortic Valve undergoing Minimally Invasive Surgical incision being converted to a Full Sternotomy open procedure During Surgery. | Prior to Surgery | 
| Subject's Average Score on the EQ-5D - Quality of Life Questionnaire Over Time | The EuroQol-5 Dimension (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, 1 Year | 
| Subject's Average Score SF-12 - Quality of Life Questionnaire Over Time | Subject's Average Score at Baseline and at each follow-up interval until 2 year - SF-12. 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. | Baseline, 30 days, 3 Months, 1 Year | 
| 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,and 1 Year. | Baseline, 30 days, 3 Months, 1 Year | 
| 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 1.5 weeks | 
| 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. | Baseline, Discharge, 30 days, 3 Months, 1 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. Higher numbers on the scale show a worsening outcome. | Discharge, 30 days, 3 month, 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic Valve Replacement, Minimal Invasive Sternotomy