Safety and Efficacy of SYM-SV/DS-002 in Patients With Severe Aortic Stenosis

Study Overview
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Brief Summary
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Safety and Efficacy of SYM-SV/DS-002 in Patients with Severe Aortic Stenosis

Detailed Description
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To evaluate the safety and efficacy of Transfemoral Transcatheter Aortic Valve Implantation using SYM-SV-002 Aortic Bioprosthesis and SYM-DS-002 Transfemoral Delivery System in patients presenting with symptomatic severe aortic stenosis and with difficulty to safely undergo conventional surgical aortic valve replacement (AVR)

Official Title
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Safety and Efficacy of SYM-SV/DS-002 in Patients With Severe Aortic Stenosis

Conditions
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Severe Aortic Stenosis

Intervention / Treatment
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* Device: SYM-SV-002 Aortic Bioprosthesis and SYM-DS-002 Transfemoral Delivery System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least one cardiologist and one cardiac surgeon agree that it is difficult for the patient to receive a surgical procedure due to medical factors such that the subject has various comorbidities and he/she is more likely to die or suffer from severe diseases than to have significant improvements by a surgical procedure. Subject has senile degenerative aortic valve stenosis with: mean gradient > 40 mmHg, or maximum jet velocity greater than 4.0 m/sec by either resting or dobutamine stress echocardiogram, or simultaneous pressure recordings at cardiac catheterization AND an initial aortic valve area of ≤ 0.8 cm2 (or aortic valve area index ≤ 0.5 cm2/m2) by resting echocardiogram or simultaneous pressure recordings at cardiac catheterization Subject is symptomatic from his/her aortic valve stenosis (AS), as demonstrated by New York Heart Association (NYHA) Functional Class II or greater. The subject has been informed of the nature of this trial, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site. The subject or the subject's legal representative agrees to visit the site where he/she receives index procedure for all required post-procedure follow-ups. Exclusion Criteria: Evidence of an acute myocardial infarction ≤ 30 days (The procedure day is counted as day 0.) before the implant procedure Any percutaneous coronary or peripheral interventional procedures, including placements of bare metal stents are performed within 30 days prior to the implant procedure, or any drug eluting stents are placed within 6 months (One month is counted as 30 days.) prior to the implant procedure Untreated clinically significant coronary artery disease (CAD) requiring revascularization Blood dyscrasias as defined: leukopenia (WBC < 1,000/mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support Need for emergency surgery for any reason Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% as measured by resting echocardiogram Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to the implant procedure (except mild TIA related to aortic stenosis) End stage renal disease requiring chronic dialysis or serum creatinine > 3.0 mg/dL Active Gastrointestinal (GI) bleeding within 3 months prior to the implant procedure A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated: Aspirin Heparin (HIT/HITTS) Nitinol (titanium or nickel) P2Y12 inhibitors (such as Ticlopidine etc.) Contrast media Ongoing sepsis, including active endocarditis Subject refuses a blood transfusion Life expectancy < 12 months due to associated non-cardiac comorbid conditions Other medical, social, or psychological conditions that in the opinion of a principal investigator or sub-investigator precludes the subject from appropriate consent Severe dementia (unable to provide informed consent for the treatment/procedure, unable to live an independent life outside of a chronic care facility, or expected to be fundamentally unable to undergo rehabilitation after the procedure, or unable to come to the site for follow-up visits) Currently participating in other trials of investigational drugs or other investigational devices Native aortic annulus size < 21 mm or > 27 mm per the baseline diagnostic imaging Pre-existing prosthetic heart valve and / or prosthetic ring in any position Mixed aortic valve disease (aortic stenosis and predominant aortic regurgitation (3-4+)) Moderate to severe (3-4+) or severe (4+) mitral regurgitation or severe (4+) tricuspid regurgitation Moderate to severe mitral stenosis Hypertrophic obstructive cardiomyopathy New or untreated echocardiographic evidence of intracardiac mass, thrombus or vegetation Congenital bicuspid or unicuspid valve verified by echocardiograph Extreme eccentric calcification of the native aortic valve Transesophageal echocardiogram (TEE) is contraindicated. Scheduled surgical or percutaneous procedure to be performed prior to 1-month visit post-implant procedure Hepatic failure (Child C or more) Aortic or peripheral condition NOT appropriate for transfemoral implant due to the size, disease and degree of calcification or tortuosity of the aorta or ilio-femoral arteries Thoracic or abdominal aortic aneurysm Woman who is pregnant, breastfeeding or willing to become pregnant
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Transcatheter Aortic Valve Implantation (TAVI)<br> | Device: SYM-SV-002 Aortic Bioprosthesis and SYM-DS-002 Transfemoral Delivery System<br>* Transcatheter Aortic Valve Implantation via Transfemoral Approach<br>* Other names: ACURATE TF™ Transfemoral Delivery System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rate |  | at 12 months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence rates of MACCE | MACCE is defined as a composite of: All Cause Mortality Myocardial infarction (MI) All Stroke Reintervention | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Occurrence rates of individual MACCE components | Individual MACCE components include: All Cause Mortality Myocardial infarction (MI) All Stroke Reintervention | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Occurrence rates of Major Adverse Events (MAEs) | MAEs include: MACCE Acute Kidney Injury (AKI) Cardiac Tamponade Prosthetic Valve Dysfunction (PVD) Cardiogenic Shock Prosthetic Valve Endocarditis Life-Threatening, Disabling or Major Bleeding Major Vascular Complications Cardiac Perforation Device Migration/Valve Embolism | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Occurrence rate of conduction disturbance requiring Permanent Pacemaker Implantation(PPI) |  | at 1 month, 6 month, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Change in NYHA class from baseline |  | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Change in distance walked during 6-Minute Walk Test (6MWT) from baseline |  | at 1 month and 12 month post-procedure | 
| Change in QOL from baseline | Kansas City Cardiomyopathy Questionnaire (KCCQ) | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Change in QOL from baseline | SF-36 | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Echocardiographic assessment of valve performance | Effective Orifice Area Index (EOAI) | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Echocardiographic assessment of valve performance | Mean gradient | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Echocardiographic assessment of valve performance | Degree of Aortic valve Regurgitation (AR) (Transvalvular and Paravalvular) | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Echocardiographic assessment of valve performance | Left ventricular ejection fraction (LVEF) | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Device success | Device success is defined as that all of the following are achieved: Successful vascular access Successful delivery and deployment of the device Successful retrieval of the delivery system Correct position of the device in the proper anatomical location (placement in the aortic annulus with no impedance on device function) Intended performance of the prosthetic heart valve is confirmed by echocardiography (defined as below): No Patient-Prosthesis Mismatch (PPM) (EOAI >0.85cm2/m2) And mean aortic valve gradient < 20 mmHg or peak velocity < 3 m/sec, And no moderate or severe prosthetic valve regurgitation Only one valve implanted in the proper anatomical location | Number of days from admission to discharge (estimated to be at 7 days post-procedure on average) | 
| Procedural success | Procedural success is defined as that all of the following are achieved: Achievement of the device success Absence of in-hospital MACCE | Number of days from admission to discharge (estimated to be at 7 days post-procedure on average) | 
| Occurrence rate of Prosthetic Valve Dysfunction (PVD) | Prosthetic Valve Dysfunction (PVD) is defined as: Aortic regurgitation (AR) reported as moderate or severe by echocardiography assessments Significant aortic stenosis (AS) which meets one or more of the following by echocardiography assessments: Peak velocity > 4 m/s Mean gradient > 35 mmHg Effective Orifice Area (EOA) < 0.8 cm2 TVIV1／TVIV2 < 0.25 | at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure | 
| Occurrence rate of clinical endpoints per VARC 2 | Mortality Stroke Myocardial infarction (MI) Bleeding complications Acute kidney injury (AKI) Vascular complications Conduction disturbances and arrhythmia Other TAVI-related complications | at 1 month post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Valvular Heart Disease, Critical Aortic Stenosis, Severe Aortic Stenosis, High Risk, Aortic Valve Replacement, Cardiovascular Disease, Aortic Stenosis, Heart Valve Therapy, Transcatheter, Transfemoral, TAVI, TAVR, ACURATE neo™ Aortic Bioprosthesis, ACURATE TF™ Transfemoral Delivery System