Overview

To evaluate safety and effectiveness of the ACURATE Transfemoral Aortic Valve System for transcatheter aortic valve replacement (TAVR) in subjects with severe native aortic stenosis who are indicated for TAVR.

Eligibility

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 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 on the
             center's assessment of pre-procedure diagnostic imaging (and confirmed by the Case
             Review Committee [CRC]) and, for the Main Randomized Cohort and the Extended
             Durability Study, is deemed treatable with an available size of both test and control
             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 an
             experienced cardiac surgeon) agrees that the subject is indicated for TAVR, is likely
             to benefit from valve replacement, and TAVR 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 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 and
             diastolic 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 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 contrast agents that cannot be adequately
             pre-medicated, or has known hypersensitivity to the protocol required medications
             (aspirin, all P2Y12 inhibitors, heparin), or to the individual components 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 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 (test or
             control) delivery systems as defined in the device (test or control) Directions 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 TAVR 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 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.
        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 ventricular
             response rate < 60 bpm.
          -  AEC3. Subject is expected to undergo chronic anticoagulation therapy after the index
             procedure.
        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.