ACURATE NEO/TF Transcatheter Heart Valves and Non-inferiority Versus Medtronic CoreValve Systems
ACURATE NEO/TF Transcatheter Heart Valves and Non-inferiority Versus Medtronic CoreValve Systems
A Multicenter, prospective, non-randomized, non-inferiority trial evaluating the safety and
 clinical efficacy of the next-generation, self-expandable Boston Scientific ACURATE NEO/TF
 Transcatheter Heart Valves, implanted in patients with severe aortic stenosis. A comparison
 with the Medtronic EVOLUT R/EVOLUT PRO systems from DIRECT trial.
The aim of this study is to evaluate the 30 day clinical and echo outcomes of Boston
 Scientific ACURATE NEO/TF TAVR and to compare them with outcomes in patients from the DIRECT
 trial treated with the Evolut TAVR system (Evolut R and Evolut PRO), aiming in showing
 non-inferiority of the ACURATE NEO/TF device. Primary endpoint will be device success rate as
 defined by the VARC-2 criteria. Secondary endpoints involve the composite endpoint of early
 safety at 30 days, according to the VARC-2 definitions, specifically all cause mortality,
 cardiovascular mortality, stroke-TIA, acute kidney injury, conduction
 disturbances-arrhythmias, life-threatening or disabling bleeding, myocardial infarction,
 major vascular complication, valve related dysfunction requiring repeat procedure
 (BAV,TAVR,SAVR) as well as the echocardiographic outcomes and valve performance as designated
 by the VARC-2 definitions at 30 days.

 Study type: Observational, non-inferiority trial

 Estimated Enrollment: 80 patients

 Allocation: Non - randomized, all comers

 Primary Purpose: Treatment

 Observational Model: Case-Control

 Condition or disease: Aortic valve stenosis

 Intervention/Treatment: Device: Boston Scientific ACURATE neoTM transfemoral TAVI system

 Time Perspective: Prospective

 Participating centers: Henry Dunant Hospital (Athens, Greece), Hippokration Hospital (Athens,
 Greece), Silesian Center for Heart Diseases (Zabrze, Poland), Athens Naval Hospital (Athens,
 Greece). It is possible that the number of the participating center may change.

 Methods: Based on an anticipated incidence proportion of 90% for the primary composite
 endpoint of device success at 30 days, the total required sample size amounts to 80 patients.
 Patients treated with the Boston Scientific ACURATE NEO/TF system will be prospectively. All
 patients will be followed for at least 30 days. Event rates will be presented by Kaplan-Meier
 curves. On the basis of previous observations regarding TAVR success rate by VARC 2
 definitions (DIRECT study), the study design uses a predefined non-inferiority margin of Δ =
 15% for the primary endpoint of device success rate at 30 days. The primary hypothesis is
 non-inferiority of ACURATE NEO/TF TAVR versus Evolut R and Evolut-Pro TAVR (based on the
 results of the DIRECT trial) for the primary endpoint at 30 days. The non-inferiority
 assumption will be tested at a one-sided significance level with a type I error rate
 (a=0.05). Non-inferiority will be met if the lower bound of the one-sided 95% confidence
 interval (CI) of the primary weighted difference of proportions endpoint (weighted average
 test-control) is over -15%. Pre-specified subgroup analyses will be conducted by using the
 appropriate interaction tests contrasting categories of mean gradient, aortic valve area
 (AVA) and left ventricular ejection fraction (>50% vs 50%).
Inclusion Criteria:

 -  Patient with severe symptomatic aortic stenosis defined by a mean aortic gradient > 40
 mmHg or peak jet velocity > 4.0 m/s or an aortic valve area (AVA) < 1cm2 or AVA
 indexed to body surface area (BSA) of <0.6 cm2/m2

 -  Patient is symptomatic (heart failure with New York Heart Association (NYHA)
 Functional Class > I, angina or syncope)

 -  Patients are considered at high risk for mortality with conventional surgical aortic
 valve replacement as assessed by a Heart Team consisting of a cardiologist and surgeon
 or as confirmed by a logistic EuroSCORE I > 20% and / or STS score > 8% OR

 -  Over 80 years old OR

 -  Over 65 years old with 1 or 2 (but not more than two) from the following criteria:

 Liver cirrhosis (Class A or B). Pulmonary insufficiency: VMS<1 liter. Previous heart
 surgery (CABG, vascular surgery). Porcelain aorta. Pulmonary artery systolic pressure >60
 mmHg and high risk for heart surgery. Relapsing pulmonary embolism. Right ventricular
 insufficiency. Thoracic wall injuries that contraindicate an open heart surgery. History of
 radiation therapy of the mediastinum. Connective tissue disease that contraindicates an
 open heart surgery. Frailty/cachexia.

 -  Aortic valve diameter of ≥20mm and ≤2 9mm as measured by echo.

 -  Ascending aorta diameter ≤ 43 mm at the sinotubular junction.

 -  Arterial aorto-iliac-femoral axis suitable for transfemoral access as assessed by
 conventional angiography and/or multi-detector computed tomographic angiography
 (access vessel diameter ≥ 6mm)

 -  Patient understands the purpose, the potential risks as well as benefits of the trial
 and is willing to participate in all parts of the follow-up

 -  Patient has given written consent to participate in the trial

 Exclusion Criteria:

 -  A known hypersensitivity or contraindication to any of the following which cannot be
 adequately pre-medicated: aspirin or heparin and bivalirudin, ticlodipine and
 clopidogrel, nitinol (titanium or nickel), contrast media

 -  Ongoing sepsis, including active endocarditis.

 -  Any percutaneous coronary or peripheral interventional procedure with a bare metal or
 drug eluting stent performed within 30 days prior to Heart Team assessment.

 -  Echocardiographic evidence of LV or LA thrombus.

 -  Mitral or tricuspid valve insufficiency (> grade II).

 -  Previous aortic valve replacement (mechanical or bioprosthetic).

 -  Recent (within 6 months of Heart Team assessment) cerebrovascular accident (CVA) or
 transient ischemic attack (TIA).

 -  Patients with:

 Femoral, iliac or aortic vascular disease (stenosis etc) that precludes the insertion of a
 transcatheter sheath.

 OR Symptomatic carotid or vertebral artery disease (> 70% stenosis).

 -  The patient has a bleeding diathesis, coagulopathy or denies blood transfusion.

 -  Estimated life expectancy of less than 12 months due to associated non-cardiac
 co-morbid conditions.

 -  Creatinine clearance < 20 ml/min.

 -  Active gastritis or gastrointestinal ulcer.

 -  Pregnancy.

 -  Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) <
 20%.

 -  Unicuspid or bicuspid aortic valve.

 -  Mixed aortic valve disease (aortic stenosis and aortic regurgitation> 2+).

 -  Liver failure (Child-Pugh class C).

 -  Severe dementia (resulting in either inability to provide informed consent for the
 study/procedure, prevents independent lifestyle outside of a chronic care facility, or
 will fundamentally complicate rehabilitation from the procedure or compliance with
 follow-up visits).

 -  Extreme aortic valve calcification and calcific asymmetry (if semiquantively measured:
 grade 4, Agatston score: grade 4 AgS>5000 AU).

 -  Aortic valve area of < 0.4 cm2.