Pivotal Study of the Vienna Transcatheter Self Expandable 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, single arm, multicenter study in an cohort of up to 267 patients (up to 100 Roll-ins and 167 patients implanted per protocol) symptomatic patients with severe aortic stenosis who will be followed up for up to 5 years.

The purpose of this trial is to determine the safety and effectiveness of the Vienna Aortic Valve SE System, a new self-expanding transcatheter heart valve, in patients with symptomatic severe aortic stenosis (SSAS). This is a prospective, single arm, multicenter study in an expanding cohort of symptomatic patients with severe aortic stenosis following the FIH feasibility study. The clinical investigation comprises 11 visits (V1 to V11). After implantation of the IMD at visit 2, safety and effectiveness assessment of the device will be performed at 30 days (V4), 3 months (V5), 6 months (V6), 1 year (V7) and every year thereafter up to 5 years post-implantation (V8 to V11).

In summary, the clinical investigation for the individual patient will end after 5 years with a full clinical evaluation. The primary study endpoints for safety and effectiveness will be reached at 30-day follow-up timepoint.

The clinical trial is completed after all 267 patients, that are not prematurely withdrawn, have completed their 5-year follow-up visit involving all specified assessments.

Inclusion criteria:

1. Male or 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% along with assessment of frailty, major organ system dysfunction, and procedure-specific impediments, in accordance with scientific guidelines
   2. Agreement by the Heart Team that subject is at moderate to high operative risk of serious morbidity or mortality with surgical valve replacement.

7. The local Heart Team 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) analyzed by a core lab.

9. Adequate iliofemoral access with either:

   1. At least one side with minimum vessel diameter ≥ 6.0 mm and acceptable level of vessel calcification and tortuosity for safe placement of the introducer sheath, as analyzed by a core lab, OR
   2. At least one side with minimum vessel diameter ≥ 5.5 and no significant calcification or severe tortuosity for safe placement of the introducer sheath, as analyzed by a core lab.

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

11. 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 prior to screening or 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 implantation prior to screening or valve 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 screening or 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.

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 IMD 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 prior to screening or IMD implantation.

11. Patient with iliofemoral vessel characteristics that would preclude safe passage of the introducer (both sides), as analyzed by a core lab:

    1. severe calcification,
    2. severe tortuosity (> two 90-degree bends),
    3. diameter < 6 mm, in patients with acceptable levels of calcification and acceptable levels of tortuosity
    4. diameter < 5.5, in patients with no calcification and no significant tortuosity, OR
    5. subject has had an aorto-femoral bypass

12. Patient with active bacterial endocarditis within 6 months prior to screening or IMD implantation.

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 or IMD 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., pulmonary artery systolic pressure ≥ 60 mmHg)

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 haemoglobin < 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 3 months prior to screening or IMD implantation.

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 (i.e. the time of informed consent).

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).