Investigation of the ALLEGRA THV System With a New Delivery System in Patients With Aortic Stenosis or Failed Surgical Bioprosthesis

The EMPIRE study confirms the technical performance of the new IMPERIA Delivery System and evaluates the safety and efficacy of the entire ALLEGRA THV System.

The primary endpoint is device success rate at 7 days (discharge from index procedure or 7 days post implant, whichever comes first), as defined by VARC 2.

Based on the outcomes of a study with a similar device and considering a drop-out rate of 5%, 107 patients need to be enrolled in the study.


Eligibility Criteria:
Inclusion Criteria:

1. Symptomatic severe calcific stenosis of a native aortic valve with an AVA ≤1.0 cm2 (or AVA index ≤0.6 cm2/m2), AND mean aortic pressure gradient ≥ 40mmHg OR maximal transaortic velocity ≥4.0m/s OR Doppler velocity index ≤0.25 on site-reported echocardiography OR symptomatic patients with degeneration of a surgical bioprosthetic valve (stenosis +/- insufficiency) on site-reported echocardiography
2. Local multi-disciplinary Heart Team and Central Screening Committee (CSC) agree on indication and eligibility for TAVI
3. Age ≥18 years
4. Patient has signed the Patient Informed Consent Form
5. Patient is willing and able to comply with requirements of the study, including all follow-up visits

Exclusion Criteria:

General:

1. Mean aortic annulus diameter as measured by pre-procedural CT or internal diameter of the bioprosthesis is \<16.5 mm or \>27 mm
2. Echocardiographic evidence of intracardiac thrombus or vegetation (site-reported)
3. Significant disease of the aorta that would preclude safe advancement of the ALLEGRA THV System
4. Severe ilio-femoral vessel disease that would preclude safe placement of an 18 Fr introducer sheath or make endovascular access impossible
5. Porcelain aorta
6. Severe left ventricular dysfunction with ejection fraction (EF) \<20% (site-reported)
7. Evidence of active endocarditis or other acute infections
8. Renal failure requiring continuous renal replacement therapy
9. Untreated clinically significant coronary artery disease requiring revascularization
10. Any percutaneous interventional procedure (e.g. PCI with stenting) within 14 days prior of the index procedure
11. Acute MI ≤30 days prior to the index procedure
12. Symptomatic carotid or vertebral artery disease requiring intervention or carotid/vertebral intervention within the preceding 45 days
13. Cerebrovascular accident (CVA) or transient ischemic attack (TIA) ≤6 months or prior CVA with moderate or severe disability (e.g. modified Rankin scale score \>2)
14. History of bleeding diathesis or coagulopathy; acute blood dyscrasias as defined: thrombocytopenia (platelets \<80,000/µl), acute anemia (hemoglobin \<10 g/dl), leukopenia (WBC \<3000/ µl)
15. Active peptic ulcer or gastrointestinal (GI) bleeding ≤3 months
16. Severe (greater than 3+) mitral insufficiency (site-reported)
17. Uncontrolled atrial fibrillation
18. Required emergency surgery for any reason
19. Known hypersensitivity to contrast media, which cannot be adequately pre-medicated or contraindication to anticoagulant or anti-platelet medication or to nitinol alloy or to bovine tissue
20. Life expectancy ≤12 months due to other medical illness
21. Currently participating in another investigational drug or device study
22. Pregnancy or intend to become pregnant during study participation

    Specific exclusions in patients with native aortic valve disease (site-reported):
23. Unicuspid or bicuspid aortic valve
24. Non-calcified aortic stenosis
25. Predominant aortic regurgitation \> grade 3
26. Distance between native aortic valve basal plane and the orifice of the lowest coronary artery \<8 mm

    Specific exclusions in patients with degenerated surgical bioprosthetic aortic valves (valve-in-valve) (site-reported):
27. Low position of the coronary ostia, especially in combination with shallow sinuses (high risk of coronary occlusion)
28. Partially detached leaflets that may obstruct a coronary ostium