Clinical Evaluation of MDT-2111 in Subjects With Symptomatic Severe Aortic Stenosis

Clinical Evaluation of MDT-2111 in Subjects With Symptomatic Severe Aortic Stenosis

The primary objective of the present trial is to demonstrate the effectiveness and safety of the MDT-2111 in the treatment of symptomatic severe aortic stenosis in subjects deemed difficult for surgical operation.

Non-randomized, prospective, multicenter, single-arm trial.

Inclusion Criteria:

1. Subject must have co-morbidities such that one cardiologist and one cardiac surgeons agree that medical factors preclude operation, based on a conclusion that the probability of death or serious morbidity exceeds the probability of meaningful improvement.

2. Subject has senile degenerative aortic valve stenosis with:

   mean gradient > 40 mmHg or jet velocity greater than 4.0 m/s by either resting or dobutamine stress echocardiogram, or simultaneous pressure recordings at cardiac catheterization (either resting or dobutamine stress), AND an initial aortic valve area of ≤ 0.8 cm² (or aortic valve area index ≤ 0.5 cm²/m²) by resting echocardiogram.

3. Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA Functional Class Class III or greater. If screening committee agrees the eligibility of a patient with class II , based on medical factors, he/she can be enrolled.

4. Subject has been informed of the nature of the trial and has signed an Informed Consent Form.

5. Subject agrees to comply with specified follow-up evaluations and to return to the same investigational site where the procedure was performed.

Exclusion Criteria:

1. Evidence of an acute myocardial infarction ≤ 30 days prior to the intended treatment.

2. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the procedure.

3. Blood dyscrasias as defined:

   • Leukopenia (WBC count < 1,000 cells/mm³)
   • Thrombocytopenia (platelet count <50,000 cells/mm³)
   • History of bleeding diathesis or coagulopathy
   • Hypercoagulable states

4. Untreated clinically significant coronary artery disease requiring revascularization.

5. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.

6. Need for emergency surgery for any reason.

7. Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% as measured by resting echocardiogram.

8. Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack(TIA).

9. End stage renal disease requiring chronic dialysis.

10. GI bleeding within the past 3 months.

11. A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated:

    • Aspirin
    • Ticlopidine
    • Heparin
    • Contrast media
    • Nitinol (titanium and nickel alloy)

12. Ongoing sepsis, including active endocarditis.

13. Subject refuses a blood transfusion.

14. Life expectancy < 12 months due to associated non-cardiac co-morbid conditions.

15. Other medical, social, or psychological conditions that in the opinion of an Investigator precludes the subject from appropriate consent.

16. Severe dementia (resulting in either inability to provide informed consent for the trial/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).

17. Currently participating in an investigational drug or another device trial. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials.

18. Symptomatic carotid or vertebral artery disease.

19. Native aortic annulus size < 20 mm or > 27 mm per the screening diagnostic imaging.

20. Pre-existing prosthetic heart valve in any position.

21. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation).

22. Mitral regurgitation (moderate to severe) or severe tricuspid regurgitation.

23. Moderate to severe mitral stenosis.

24. Hypertrophic obstructive cardiomyopathy.

25. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.

26. Severe basal septal hypertrophy with an outflow gradient.

27. Ascending aorta diameter > 43 mm (in case of the aortic annulus is 23-27 mm) unless the aortic annulus is 20-23 mm in which case the ascending aorta diameter > 40 mm.

28. Congenital bicuspid or unicuspid valve verified by echocardiography.

29. For patients with native coronary artery dependent circulation:

    • Sinus of valsalva width < 29 mm unless the aortic annulus is 20-23 mm, in which case the sinus of valsalva width < 27 mm, OR
    • Height of the left or right coronary sinus of valsalva (to the tubular aorta) < 15mm.

30. Femoral or iliac artery of the first choice corresponding to any one of the followings:

    • Angle at aortic root (the angle between aortic valve annulus plane and horizontal plane/vertebra) exceeds 70°.
    • Vessel diameter of femoral or iliac artery is less than 6 mm.
    • Aorta has severe calcification, excess tortuosity or severe atherosclerosis.
    • Transarterial access not able to accommodate an 18Fr sheath.

31. Subclavian artery of the second choice corresponding to any one of the followings:

    • Angle at aortic root (the angle between aortic valve annulus plane and horizontal plane/vertebra) exceeds 70° (in the case of left subclavian artery) and 30° (in the case of right subclavian artery).
    • Vessel diameter of subclavian artery is less than 6 mm.
    • Transarterial access not able to accommodate an 18Fr sheath.

32. Direct Aortic Artery as third line choice of access. Patients are excluded from Direct Aortic access if:

    • Access site is less than 6 cm from the aortic valve basal plane
    • Access site has calcification or porcelain aorta
    • Access site and delivery trajectory contain RIMA or patent RIMA graft