ACURATE Prime XL Human Feasibility Study

The ACURATE Prime XL Human Feasibility Study (ACURATE Prime XL HFS) is a prospective, multicenter, open-label, single-arm study designed to evaluate feasibility and safety of the ACURATE Prime XL Transfemoral Aortic Valve System for TAVI in subjects who have severe native aortic stenosis and are indicated for TAVI.

Subjects who provide written informed consent, meet all eligibility criteria, and are approved by the Case Review Committee (CRC) are considered enrolled when an attempt is made to insert the iSLEEVE Introducer into the subject's femoral artery. There will be up to 20 subjects enrolled at up to 6 centers in Australia and Europe.

All subjects implanted with a study valve will be assessed at baseline, peri- and post-procedure, at discharge or 7 days post index procedure (whichever comes first), 30 days, 6 months, and 1 year. Subjects who are enrolled but not implanted with a study valve at the time of the procedure will be followed for safety through 30 days.

Inclusion criteria

• IC1. Subject has documented severe symptomatic native aortic stenosis defined as follows: aortic valve area (AVA) ≤1.0 cm2 (or AVA index ≤0.6 cm2/m2) AND a mean pressure gradient ≥40 mmHg, OR maximal aortic valve velocity ≥4.0 m/s, OR Doppler velocity index ≤0.25 as measured by echocardiography and/or invasive hemodynamics. Note: In cases of low flow, low gradient aortic stenosis with left ventricular dysfunction (ejection fraction <50%), dobutamine can be used to assess the grade of aortic stenosis (maximum dobutamine dose of 20 mcg/kg/min recommended); the subject may be included in the study if echocardiographic criteria are met with this augmentation.
• IC2. Subject has a documented aortic annulus diameter of ≥26.5 mm and ≤29 mm based on the center's assessment of pre-procedure diagnostic imaging (and confirmed by the Case Review Committee [CRC]).
• IC3. For subjects with symptomatic aortic valve stenosis per IC1 definition above, functional status is NYHA Functional Class ≥ II.
• IC4. Heart team (composition per local standards, but at a minimum must include an experienced cardiac surgeon) agrees that the subject is indicated for TAVI, is likely to benefit from prosthetic valve implantation, and TAVI is appropriate.
• IC5. Subject (or legal representative) understands the study requirements and the treatment procedures and provides written informed consent.
• IC6. Subject, family member, and/or legal representative agree(s) and subject is capable of returning to the study hospital for all required scheduled follow up visits.
• IC7. Subject is expected to be able to take the protocol-required adjunctive pharmacologic therapy.

Exclusion criteria

• EC1. Subject has a unicuspid or bicuspid aortic valve.
• EC2. Subject has had an acute myocardial infarction within 30 days prior to the index procedure (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).
• EC3.Subject has had a cerebrovascular accident or transient ischemic attack clinically confirmed by a neurologist or neuroimaging within the past 6 months prior to study enrollment.
• EC4.Subject has eGFR < 20 mL/min (based on hospital preferred method) but is not on renal replacement therapy.
• EC5. Subject has a pre-existing prosthetic aortic or mitral valve.
• EC6. Subject has severe (4+) aortic, tricuspid, or mitral regurgitation.
• EC7. Subject has moderate or severe mitral stenosis (mitral valve area ≤1.5 cm2 and diastolic pressure half-time ≥150 ms, Stage C or D).
• EC8. Subject has a need for emergency surgery for any reason.
• EC9. Subject has a history of endocarditis within 6 months of index procedure or evidence of an active systemic infection or sepsis.
• EC10. Subject has echocardiographic evidence of new intra-cardiac vegetation or intraventricular or paravalvular thrombus requiring intervention.
• EC11. Subject has platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <1,000 cells/mm3.
• EC12. Subject has had a gastrointestinal bleed requiring hospitalization or transfusion within the past 3 months or has other clinically significant bleeding diathesis or coagulopathy that would preclude treatment with required antiplatelet regimen or will refuse transfusions.
• EC13. Subject has known hypersensitivity to the following:

• Contrast agents that cannot be adequately pre-medicated, OR
• Protocol-required medications (aspirin, all P2Y12 inhibitors, heparin), OR
• Individual components of the investigational valve and/or delivery system (stainless steel, platinum, iridium, nickel, titanium, or polyethylene terephthalate [PET]).
• EC14. Subject has a life expectancy of less than 12 months due to non-cardiac, comorbid conditions based on the assessment of the investigator at the time of enrollment.
• EC15. Subject has hypertrophic cardiomyopathy.
• EC16. Subject has any therapeutic invasive cardiac or vascular procedure within 30 days prior to the index procedure (except for balloon aortic valvuloplasty, pacemaker implantation, or implantable cardioverter defibrillator implantation, which are allowed).
• EC17. Subject has untreated coronary artery disease, which in the opinion of the treating physician is clinically significant and requires revascularization.
• EC18. Subject has severe left ventricular dysfunction with ejection fraction <20%.
• EC19. Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices.
• EC20. Subject has arterial access that is not acceptable for the study device delivery system as defined in the Instructions For Use.
• EC21. Subject has either of the following:

• Severe vascular disease that would preclude safe access (e.g., aneurysm with thrombus that cannot be crossed safely; marked tortuosity; significant narrowing of the abdominal aorta; severe unfolding of the thoracic aorta; or thick, protruding, ulcerated atheroma in the aortic arch), OR
• Severe/eccentric calcification of the aortic annulus that would prevent safe implantation of the TAVI prosthesis.
• EC22. Subject has current problems with substance abuse (e.g., alcohol, etc.) that may interfere with the subject's participation in this study.
• EC23. Subject is participating in another investigational drug or device study that has not reached its primary endpoint or subject intends to participate in another investigational device clinical trial within 12 months after the index procedure.
• EC24. Subject has untreated conduction system disorder (e.g., Type II second degree atrioventricular block) that in the opinion of the treating physician is clinically significant and requires a pacemaker implantation. Enrollment is permissible after permanent pacemaker implantation.
• EC25. Subject has severe incapacitating dementia.