ACURATE Neo™ TA Delivery System in Patient With Severe Aortic Stenosis

Study Overview
=================
Brief Summary
-----------------
The purpose of this investigation is to collect data pertaining to the safety and performance of the ACURATE neo (TM) Aortic Bioprosthesis as implanted with the ACURATE neo (TM) TA Transapical Delivery System. This device is intended for treatment of subjects with severe aortic stenosis (AS) who have high risk for conventional aortic valve replacement (AVR) surgery. The ACURATE neo (TM) Aortic Bioprosthesis is intended for use via minimally-invasive transapical implantation in a well-defined population.

Detailed Description
-----------------
This is a single arm, prospective, multicenter non randomised and open trial of the treatment of patients with severe aortic stenosis where conventional aortic valve replacement (AVR) via open heart surgery is considered to be high risk. All patients will be followed up to 5 years after the intervention. The primary objective is to evaluate the safety and performance of the study device in patients presenting with severe aortic stenosis considered to be high risk for surgery Secondary objective is to evaluate adverse events and study device performance.

Official Title
-----------------
ACURATE Neo™ Aortic Bioprosthesis for Implantation Using the ACURATE Neo™ TA Transapical Delivery System in Patients With Severe Aortic Stenosis

Conditions
-----------------
Aortic Stenosis

Intervention / Treatment
-----------------
* Device: ACURATE neo™TA Delivery System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must be at least 18 years old Severe aortic stenosis defined as: Mean aortic gradient > 40 mmHg or Peak jet velocity > 4.0 m/s or Aortic valve area of < 0.8 cm2 High risk patient determined by a multidisciplinary heart team consensus (cardiologist and cardiac surgeon) that patient is not a surgical candidate for conventional AVR due to risk factors such as STS Score (8% or higher) or other co-morbid conditions unrelated to aortic stenosis such as severe chronic obstructive pulmonary disease (COPD), chest deformities and irradiated mediastinum NYHA Functional Class > II Multidisciplinary heart team (cardiologist and cardiac surgeon) consensus that the transapical approach is the most suitable access route for TAVI due to the presence of the following anatomic conditions: porcelain aorta or severely calcified or highly tortuous peripheral vasculature not appropriate for transfemoral transcatheter aortic valve implantation or vessels too small for retrograde approach or other anatomical conditions making transapical approach more suitable Aortic annulus diameter from ≥ 21mm up to ≤ 27mm by CT or TEE Patient willing to participate in the study and provides signed informed consent Exclusion Criteria: Congenital unicuspid or bicuspid aortic valve or non-calcified Extreme eccentricity of calcification Severe mitral regurgitation (> Grade 3) Pre-existing prosthetic heart valve in any position and / or prosthetic ring LV apex is not accessible via transapical access due to severe chest deformity Previous surgery of the LV using a patch, such as the Dor procedure Presence of apical LV thrombus Calcified pericardium Septal hypertrophy unacceptable for transapical procedure Transesophageal echocardiogram (TEE) is contraindicated ECHO evidence of intracardiac mass, thrombus, or vegetation LVEF < 20% by ECHO Need for emergency intervention for any reason within 30 Days of scheduled procedure Any percutaneous intervention, except for balloon valvuloplasty (BAV) within 1 month prior to implant procedure Untreated clinically significant coronary artery disease requiring revascularization within 30 days before or after the study procedure Acute myocardial infarction within 1 month prior to implant procedure Previous TIA or stroke within 6 months prior to implant procedure Active gastrointestinal (GI) bleeding within 3 months prior to implant procedure Scheduled surgical or percutaneous procedure to be performed prior to 30 day visit History of bleeding diathesis, coagulopathy, refusal of blood transfusions or severe anemia (Hb<8 g/dL) Systolic pressure <80mmHg, cardiogenic shock, need for inotropic support or IABP Primary hypertrophic obstructive cardiomyopathy (HOCM) Active infection or endocarditis Hepatic failure (> Child B) Chronic renal dysfunction with serum creatinine > 3.0 mg/dL or renal dialysis Neurological disease severely affecting ambulation, daily functioning, or dementia Life expectancy < 12 months due to non-cardiac co-morbid conditions Intolerance to aspirin, clopidogrel, contrast media, or porcine tissue and allergy to nickel Pregnant or breast-feeding women For other severe illnesses of the patient (e.g. active carcinoma), the investigator shall decide on an individual basis whether the patient is not to be included in the study Currently participating in an investigational drug or another device study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACURATE neo™TA Delivery System<br>Patients implanted with ACURATE neo™ Aortic Bioprosthesis and ACURATE neo™ TA Transapical Delivery System | Device: ACURATE neo™TA Delivery System<br>* ACURATE neo™ Aortic Bioprosthesis and ACURATE neo™TA Transapical Delivery System on patients with severe aortic stenosis where conventional aortic valve replacement (AVR) via open-heart surgery is considered to be high risk<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety: freedom from all-cause mortality | freedom from all-cause mortality | 6 months post procedure | 
| Primary Device Performance:Procedure success in absence of MACCE | Procedure success in absence of MACCE | 30 days post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of clinical endpoints according to the Valve Academic Research Consortium (VARC 2) guidelines | VARC 2 guidelines include different safety and efficacy endpoints like mortality, MI, stroke, etc. | 30 Days and month 12 | 
| Incidence of all cause mortality at 30 Days and 12 Months | Incidence of all cause mortality at 30 Days and 12 Months | 30 days and 12 months | 
| Freedom from MACCE at 30 Days, 6 Months and 12 Months | Freedom from MACCE at 30 Days, 6 Months and 12 Months | 30 Days, 6 Months and 12 Months | 
| Number of patients who have a Procedural success defined by a combination of criteria | Procedural success defined as ACURATE neo™ at intended location with | procedure | 
| Rate of device success | Rate of device success | 7 days/ Discharge, 30 Days, 6 Months and at 12 Months | 
| NYHA Functional Classification improvement | NYHA Functional Classification improvement | 30 Days, 6 Month and at 12 Months | 
| Echocardiographic assessment of valve performance (at 7 Days or Discharge, 30 Days, 6 Months, 12 Months) using a combination of measures | Echocardiographic assessment of valve performance (at 7 Days or Discharge, 30 Days, 6 Months, 12 Months) using a combination of measures | 7 Days or Discharge, 30 Days, 6 Months, 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TAVI, Aortic Stenosis, transcatether Aortic Valve Implantation