ACURATE IDE: Safety and Effectiveness Study of ACURATE Valve for Transcatheter Aortic Valve Replacement

Inclusion Criteria:

• IC1. Subject has documented severe symptomatic native aortic stenosis defined asfollows: aortic valve area (AVA) ≤1.0 cm2 (or AVA index ≤0.6 cm2/m2) AND a meanpressure gradient ≥40 mmHg, OR maximal aortic valve velocity ≥4.0 m/s, OR Dopplervelocity 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 enrolled if echocardiographic criteria are met with this augmentation.

• IC2. Subject has a documented aortic annulus size of ≥20.5 mm and ≤29 mm based onthe center's assessment of pre-procedure diagnostic imaging (and confirmed by theCase Review Committee [CRC]) and, for the Main Randomized Cohort and the ExtendedDurability Study, is deemed treatable with an available size of both test andcontrol device.

• IC3. For subjects with symptomatic aortic valve stenosis per IC1 definition above,functional status is NYHA Functional Class ≥ II.

• IC4. Heart team (which must include an experienced cardiac interventionalist and anexperienced cardiac surgeon) agrees that the subject is indicated for TAVR, islikely to benefit from valve replacement, and TAVR is appropriate.

• IC5. Subject (or legal representative) understands the study requirements and thetreatment procedures, and provides written informed consent.

• IC6. Subject, family member, and/or legal representative agree(s) and subject iscapable of returning to the study hospital for all required scheduled follow upvisits.

• IC7. Subject is expected to be able to take the protocol-required adjunctivepharmacologic 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 theindex 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 attackclinically confirmed by a neurologist or neuroimaging within the past 6 months priorto study enrollment.

• EC4. Subject is on renal replacement therapy or has eGFR <20.

• 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 anddiastolic pressure half-time ≥150 ms, Stage C or D76).

• EC8. Subject has a need for emergency surgery for any reason.

• EC9. Subject has a history of endocarditis within 6 months of index procedure orevidence of an active systemic infection or sepsis.

• EC10. Subject has echocardiographic evidence of new intra-cardiac vegetation orintraventricular or paravalvular thrombus requiring intervention.

• EC11. Subject has platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or whiteblood cell count <1,000 cells/mm3.

• EC12. Subject has had a gastrointestinal bleed requiring hospitalization ortransfusion within the past 3 months, or has other clinically significant bleedingdiathesis or coagulopathy that would preclude treatment with required antiplateletregimen, or will refuse transfusions.

• EC13. Subject has known hypersensitivity to contrast agents that cannot beadequately pre-medicated, or has known hypersensitivity to the protocol requiredmedications (aspirin, all P2Y12 inhibitors, heparin), or to the individualcomponents of the test or control valve (nickel, titanium, stainless steel,platinum, iridium 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 ofenrollment.

• EC15. Subject has hypertrophic cardiomyopathy.

• EC16. Subject has any therapeutic invasive cardiac or vascular procedure within 30days 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 thetreating 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 requiringinotropic support or mechanical support devices.

• EC20. Subject has arterial access that is not acceptable for the study device (testor control) delivery systems as defined in the device (test or control) DirectionsFor Use.

• EC21. Subject has either of the following:

• Severe vascular disease that would preclude safe access (e.g., aneurysm withthrombus that cannot be crossed safely; marked tortuosity; significantnarrowing of the abdominal aorta; severe unfolding of the thoracic aorta; orthick, protruding, ulcerated atheroma in the aortic arch), OR

• Severe/eccentric calcification of the aortic annulus that would prevent safeimplantation of the TAVR prosthesis.

• EC22. Subject has current problems with substance abuse (e.g., alcohol, etc.) thatmay interfere with the subject's participation in this study.

• EC23. Subject is participating in another investigational drug or device study thathas not reached its primary endpoint or subject intends to participate in anotherinvestigational device clinical trial within 12 months after index procedure.

• EC24. Subject has untreated conduction system disorder (e.g., Type II second degreeatrioventricular block) that in the opinion of the treating physician is clinicallysignificant and requires a pacemaker implantation. Enrollment is permissible afterpermanent pacemaker implantation.

• EC25. Subject has severe incapacitating dementia.

Additional exclusion criteria apply to subjects considered for enrollment in the CT Imaging Substudy as listed below.

• AEC1. Subject has eGFR <30 mL/min (chronic kidney disease stage IV or stage V)

• AEC2. Subject has atrial fibrillation that cannot be rate controlled to ventricularresponse rate < 60 bpm.

• AEC3. Subject is expected to undergo chronic anticoagulation therapy after the indexprocedure.

Note: Subjects treated with short-term anticoagulation post procedure can be included in the CT Imaging Substudy; in these subjects the 30-day imaging will be performed 30 days after discontinuation of anticoagulation.