A Two -Stage First in Human (FIH) Feasibility / Pivotal Study of the Vienna Aortic Valve SE System
A Two -Stage First in Human (FIH) Feasibility / Pivotal Study of the Vienna Aortic Valve SE System
This is a prospective, non-randomized, single arm, multicenter, multinational two-stage FIH
 feasibility followed by pivotal study in symptomatic patients with severe aortic stenosis.
The study consists of 7 visits spread out across two phases over 1 year. The clinical
 investigation will end at 30 days post-implantation. The subsequent 3-month, 6-month and
 1-year follow-up (FU) visits will thus be considered post-market clinical follow-up (PMCF).

 The FIH study will start by evaluating the safety and feasibility of the device and study
 design of the Vienna Aortic Valve SE System in 10 patients with SSAS. The FIH patients must
 meet all study eligibility criteria. Safety and feasibility assessments for patients in the
 FIH period will include implantation success, hemodynamic performance and monitoring of
 adverse events (AEs). Early FIH data (i.e. data from the first 10 patients to have completed
 visit 3 at hospital discharge) will be provided to the Data and Safety Monitoring Board
 (DSMB) for review during which study enrollment will be paused. After reviewing the safety
 results from the FIH study, the DSMB will make a recommendation on whether the study may
 continue as planned. FIH patients will continue to be followed up for 1 year as per protocol.
 Data from the 10 FIH patients and the subsequent 75 patients will be analyzed together for
 the pivotal study endpoints.

 Upon a decision from the DSMB to proceed with the study, enrolment of patients will resume.

 The clinical investigation phase comprises 4 visits (V1 to V4). After implantation of the IMD
 at visit 2, early performance and safety assessment of the device will be performed at 30
 days (V4). The post-market surveillance phase comprises 3 visits (V5-V7), extending from 3
 months to 1 year post-implantation, to evaluate the long-term safety and performance profile
 of the device.
Inclusion Criteria:

 1. Male and Female

 2. Age ≥ 65 years at time of consent

 3. Women of non-childbearing potential

 4. Severe degenerative calcific native aortic valve stenosis with the following criteria
 assessed either by resting or dobutamine stress TTE:

 1. Aortic valve area (AVA) < 1.0 cm2 or AVA index ≤ 0.6 cm2/m2 and

 2. Jet velocity > 4.0 m/s or mean gradient > 40 mmHg

 5. Symptomatic aortic stenosis (AS), defined as a history of at least one of the
 following:

 1. Dyspnea that qualifies at NYHA class II or greater

 2. Angina pectoris

 3. Cardiac syncope

 6. Subject is considered at intermediate or high risk for surgical valve replacement
 based on at least one of the following:

 1. EuroSCORE II ≥ 4%

 2. Agreement by the Heart Team that subject is at high operative risk of serious
 morbidity or mortality with surgical valve replacement

 7. The local Heart Team, including at least 1 cardiothoracic surgeon and 1 interventional
 cardiologist, deems the patient to be eligible for transfemoral TAVI.

 8. Perimeter-based aortic annulus diameter between ≥ 18 and ≤ 29 mm measured by computed
 tomography (CT) performed within 90 days prior to planned implantation

 9. Adequate iliofemoral access with minimum average vessel diameter of ≥ 6.0mm and
 acceptable level of vessel calcification and tortuosity for safe placement of the
 introducer sheath

 10. The distance from coronary ostia to aortic anulus > 12 mm

 11. Patient (or legal representative) understands the study requirements and the treatment
 procedures and provides written informed consent.

 12. The patient and the treating physician agree that the patient will return for all
 required post-procedure follow-up visits.

 Exclusion Criteria:

 Cardiovascular System:

 1. Patient has a congenital unicuspid or bicuspid aortic valve or non-calcified valves.

 2. Evidence of an acute myocardial infarction (MI) ≤ 30 days before the IMD implantation
 (defined as Q-wave MI or non-Q-wave MI with total CK elevation ≥ twice normal in the
 presence of CK-MB elevation and/or troponin elevation).

 3. Patient has had a cerebrovascular stroke or TIA within the past 90 days before IMD
 implantation.

 4. Patient has a hypertrophic obstructive cardiomyopathy.

 5. History of any therapeutic invasive cardiac procedure (including balloon aortic
 valvuloplasty) within 30 days prior to the planned IMD implantation (except for
 pacemaker implantation which is allowed).

 6. Untreated clinically significant coronary artery disease requiring revascularization
 at the screening visit.

 7. Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) <
 20% by echocardiography, contrast ventriculography, or radionuclide ventriculography
 within 90 days prior.

 8. Patient with cardiogenic shock manifested by low cardiac output and hemodynamic
 instability and vasopressor dependence, or mechanical hemodynamic support

 9. Patients with clinically significant conduction abnormalities (clinically significant
 sinus bradycardia, sinus block or pauses, clinically significant atrioventricular
 (AV)-block >I) at screening and at time of valve implantation.

 10. Patient has severe peripheral vascular disease:

 1. including aortic aneurysm defined as maximal luminal diameter > 5 cm or with
 documented presence of thrombus, marked tortuosity, narrowing of the abdominal
 aorta, severe unfolding of the thoracic aorta or thick [> 5 mm], protruding or
 ulcerated atheroma in the aortic arch) or

 2. symptomatic carotid or vertebral disease or successful treatment of carotid
 stenosis within 30 days before IMD implantation.

 11. Patient with iliofemoral vessel characteristics that would preclude safe passage of
 the introducer [severe calcification, tortuosity (> two 90-degree bends), diameter <
 6mm, or subject has had an aorto-femoral bypass]

 12. Patient with active bacterial endocarditis within 6 months of planned IMD

 13. Patient has (echocardiographic/ CT and/or MRI) evidence of intra-cardiac mass,
 thrombus or vegetation.

 14. Patient has a pre-existing prosthetic heart valve in any position (Note: mitral ring
 is not an exclusion).

 15. Patient has severe mitral regurgitation, severe aortic regurgitation or severe
 tricuspid regurgitation, moderate or severe mitral stenosis.

 16. Patient has a need for emergency surgery for any reason at time of screening and valve
 implantation.

 General:

 17. Any condition considered a contraindication for placement of a bioprosthetic valve
 (e.g. patient with contraindication to oral antiplatelet therapy)

 18. Patient with renal insufficiency (eGFR < 30 ml/min per the Cockcroft-Gault formula)
 and/ or renal replacement therapy and/ or has serum creatinine level > 3.0 mg/dL or
 265 µmol/L replacement therapy at the time of screening

 19. Patient with significant pulmonary disease (FEV1 < 30%) or currently on home oxygen

 20. Severe pulmonary hypertension (e.g., PA systolic pressure / systemic pressure >1 or
 mean pulmonary pressure > 55 mmHg assessed by echocardiography)

 21. Patients with evidence of an active systemic infection or sepsis

 22. Patient has a known hypersensitivity or contraindication to contrast media, bovine
 tissue, nitinol (titanium or nickel), contraindication to oral antiplatelet therapy
 (aspirin, ticlopidine or clopidogrel) or heparin.

 23. Patient has a hemoglobin < 9 g/dL, platelet count < 50,000 cells/mm3 or > 700.000
 cells/mm3, or white blood cell count < 1.000 cells/mm3, history of bleeding diathesis
 or coagulopathy

 24. Patient has peptic ulcer disease or history of gastrointestinal bleeding within the
 past 3 months.

 25. Patient refuses blood transfusions.

 26. Patient has a life expectancy of less than 12 months due to non-cardiac, co-morbid
 conditions based on the assessment of the investigator at the time of enrolment.

 27. Patient is pregnant or breast feeding.

 28. 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).

 29. Other medical, social, or psychological conditions that in the opinion of the
 Investigator precludes the patient from appropriate consent or adherence to the
 protocol required follow-up exams

 30. Patient is currently participating in another investigational drug or device study
 that has not reached its primary endpoint (excluding observational studies).