Transcatheter Aortic Valve Replacement System Pivotal Trial

Prospective, randomized, unblended, multi-center investigational study with enrollment at up
to 45 Investigational sites. The study is designed to compare the study device (Direct Flow
Medical Transcatheter Aortic Valve System) composite event rate to a comparator (Medtronic
CoreValve commercially available) in high and extreme risk subjects with severe symptomatic
aortic stenosis.

The primary study endpoint is a composite of all-cause mortality, disabling stroke, or
moderate or greater paravalvular aortic regurgitation (based on core lab assessment) at 1
year. All primary endpoint events will be evaluated by a CEC using the definitions located
in this protocol.

The powered secondary endpoint is the rate of mild or greater paravalvular aortic
regurgitation at 30 days. The objective is to show that the study device rate of
paravalvular aortic regurgitation at 30 days is lower than that observed for the comparator.

Subjects must meet the fundamental enrollment criteria of severe symptomatic, calcific
aortic stenosis with quantifiable and documented source records.

Inclusion Criteria:

1. The subject has severe senile degenerative aortic valve stenosis etermined by resting
or dobutamine stress echocardiogram and Doppler, or simultaneous pressure recordings
at cardiac catheterization defined as: mean aortic gradient ≥40 mmHg or peak jet
velocity ≥4.0 m/s and an aortic valve area ≤1.0 cm2 or aortic valve area index ≤0.6
cm2/m2.

2. The subject has moderate to severe symptoms from aortic valve stenosis (NYHA
Functional Class ≥II)

3. Subject has a documented aortic annulus size of ≥19 mm and <29 mm based on the
center's assessment of pre-procedure diagnostic imaging (and confirmed by the Patient
Review Committee [PRC]) and is deemed treatable with an available size of both test
and control device..

4. There is agreement by the heart team (which must include a site cardiac
interventionalist and two cardiac surgeons that are staff members at the hospital
where the procedure is to be performed) that subject is at high operative risk or
greater of serious morbidity or mortality with surgical valve replacement (see note
below for definitions of extreme and high risk, the required level of surgical
assessment, and PRC confirmation) and that TAVR is appropriate. Subjects are judged
by a heart team, including two cardiac surgeons, to be at high or greater risk for
open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score >8% or
at a > 15% risk of mortality at 30 days).This conclusion shall be based on consensus
of one cardiac interventionalist and two cardiac surgeons that have examined the
subject face to face after careful consideration of the Subject's STS risk score and
co-morbidities. NOTE: In the United States, the Centers for Medicare and Medicaid
Services (CMS) require independent evaluations by 2 cardiac surgeons for
reimbursement.

5. Subject understands the study requirements and the treatment procedures, and provides
written informed consent.

6. Subject agrees and is capable of returning to the study hospital for all required
scheduled follow up visits.

Exclusion Criteria:

1. Left ventricular ejection fraction (LVEF) <20% determined by resting echocardiogram.

2. Subjects with an acute STEMI within 30 days preceding the index procedure.

3. Chronic kidney disease (creatinine >3.0 mg/dl, renal replacement therapy at the time
of screening or unstable renal function).

4. Subjects with a platelet count of <50,000 cells/mm³ or a WBC < 1000 cells/mm³ within
7 days prior to index procedure.

5. Subject has a known contraindication or hypersensitivity to all antithrombin regimens
(aspirin, all P2Y12 inhibitors), or inability to be anti-coagulated for the study
procedure. Note: Subjects who require chronic anticoagulation must be able to be
treated additionally with either aspirin or clopidogrel.

6. Any subject with a balloon valvuloplasty (BAV) within 30 days of the procedure unless
the BAV is a bridge to the procedure. The bridge BAV must be performed > 72 hours
prior to the index procedure.

7. Subjects who are on a waiting list for any organ transplant.

8. Subjects with known other medical illness associated with a life expectancy of less
than one year, or expectation that subject will not improve despite treatment of
aortic stenosis.

9. Subject has known hypersensitivity to contrast agents that cannot be adequately
pre-medicated, or has known hypersensitivity to nickel, tantalum, titanium, or
polyurethanes

10. Subjects with a history of a stroke or transient ischemic attack TIA) within the
prior 6 months of procedure or screening.

11. Subjects with an active gastrointestinal (GI) bleeding (endoscopy proven or bleeding
precluding Dual antiplatelet therapy) within the prior 3 months.

12. Subjects presenting with hemodynamic instability or cardiogenic shock requiring
inotropic support or mechanical support devices.

13. Subjects who have a planned treatment with any other investigational device or
procedure through 1 year follow-up, or who are currently participating in an
investigational drug or another device trial.

14. Any planned surgical, percutaneous coronary or peripheral procedure to be performed
within the 30 day follow-up from the TAVR procedure.

15. Untreated clinically significant coronary artery disease requiring revascularization.

16. Trans-esophageal echocardiography (TEE) is contraindicated.

17. Active endocarditis or sepsis within 6 months prior to the study procedure.

18. Any condition resulting in inability to provide informed consent for the trial or
difficulty in assessment of neurologic status.

Anatomic and Vascular Exclusions

19. Congenital bicuspid or unicuspid valve (except as outlined in the planned nested
registry).

20. Prior aortic valve surgery or pre-existing prosthetic heart valve in the mitral or
aortic position (mitral and tricuspid rings are permissible).

21. A native valve annulus diameter <19mm or ≥29mm determined by the screening CT scan.

22. Echocardiographic evidence of new intra-cardiac mass untreated thrombus, or
vegetation that requires treatment.

23. >3+: aortic regurgitation, mitral regurgitation or tricuspid regurgitation.

24. Severe mitral stenosis.

25. Thoracic aortic aneurysm (TAA) >5.50 cm.