ARTIST: Aortic Regurgitation Trial Investigating Surgery Versus Trilogy™

A Study to Assess Safety and Effectiveness of the JenaValve Trilogy™ Transcatheter Heart Valve System Versus Surgical Valve Replacement in Patients With Aortic Regurgitation

To demonstrate non-inferiority of the Trilogy Transcatheter Heart Valve (THV) System compared with surgical aortic valve replacement (SAVR) for treatment of subjects with clinically significant native aortic regurgitation (AR)

Inclusion Criteria:

1. Clinical indication for AVR for native valve predominant AR defined as:

   1. Class I or II indication for AVR according to ACC/AHA or ESC/EACTS guidelines with moderate to severe or severe AR (Grade ≥3+) on transthoracic echocardiography, transesophageal echocardiography or cardiac MRI as assessed by the core laboratory OR
   2. AR severity that remains indeterminate despite core laboratory review of all imaging including at least one advanced imaging modality (TEE or cardiac MRI) AND evidence of left ventricular damage* from AR with unanimous agreement from the local heart team, an independent clinical evaluation committee and the CRB that the symptomatic subject (NYHA II or greater) will benefit from SAVR for AR

2. The subject is a candidate for TAVR using the Trilogy THV system and SAVR using a commercially approved bioprosthetic heart valve

3. Subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits

4. Subject meets the legal minimum age to provide informed consent based on local regulatory requirements

Exclusion Criteria:

1. Confirmed moderate (2+) or less AR severity by core laboratory evaluation

2. Estimated life expectancy of less than 24 months due to associated non- cardiac comorbid conditions

3. Subject is high-risk for SAVR as determined by the local heart team

4. Subject refuses SAVR as a treatment option

5. Subject refuses a blood transfusion

6. Subject is selected for aortic valve repair or aortic surgery

7. Marfan syndrome or other known connective tissue disease that would necessitate aortic root replacement/intervention

8. Subject unable to undergo pre-procedure CT scan analysis for annular sizing

9. Mitral or tricuspid disease, considered clinically significant, such that if randomized to surgery, repair or replacement would be expected.

10. Subject has a known hypersensitivity or contraindication to all anticoagulation/antiplatelet medications (or inability to be anticoagulated for the index procedure), nitinol, or sensitivity to contrast media which cannot be adequately pre-medicated

11. Hostile chest or conditions or complications from a prior surgery that would preclude safe reoperation (i.e., mediastinitis, radiation damage, chest wall abnormalities, adhesion of aorta or internal mammary artery (IMA) to the sternum)

12. Need for emergency surgery or TAVR for any reason

13. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or need for mechanical circulatory support

14. Ongoing sepsis or active infective endocarditis with ongoing antibiotic (including suppressive) therapy or positive blood cultures within 6 weeks

15. Cardiac resynchronization therapy (CRT) device implantation within 30 days of randomization

16. LVEF <25% according to core laboratory measurement of resting echocardiogram at time of screening

17. Moderate to severe or worse right ventricular dysfunction on resting echocardiogram according to core laboratory

18. Severe chronic liver disease (Child-Pugh C) or any active liver disease

19. Chronic Kidney Disease Stage 4 or 5 (<30 cc/min/1.73 m2 or dialysis)

20. Severe Pulmonary Hypertension (pulmonary arterial systolic pressure

    • amp;amp;gt;2/3 systemic systolic pressure)

21. Severe Chronic Obstructive Pulmonary Disease (COPD) with FEV1

    • amp;amp;lt;50% predicted or need for chronic supplementary oxygen

22. Blood dyscrasia as defined: leukopenia (WBC <3,000 Cells/μL), thrombocytopenia (platelet count <50,000 Cells/μL), or anemia (hemoglobin <9.0 g/dL) that is uncorrected prior to randomization

23. History of bleeding diathesis or coagulopathy that is not adequately treated

24. Active gastrointestinal bleeding precluding anticoagulation or antiplatelet therapy

25. Any condition considered a contraindication to mechanical circulatory support

26. Uncontrolled atrial fibrillation (i.e., resting heart rate >120 bpm)

27. Evidence of an acute myocardial infarction ≤30 days before the index AVR

28. Any percutaneous coronary or peripheral interventional procedure performed ≤30 days prior to AVR (Subjects with placement of coronary or peripheral stent(s) should be assessed for the ability to safely proceed with SAVR within the protocol timeframe)

29. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within six weeks of randomization

30. Prior stroke with residual modified Rankin Score ≥2

31. Stroke or transient ischemic attack (TIA) within 6 months of randomization

32. Body mass index (BMI) <20 or >50 kg/m2

33. Currently participating in a cardiovascular investigational drug or device trial and has not yet completed follow-up for the primary endpoint (excluding registries)

34. Severe cognitive decline (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)

35. Other medical, social, or psychological conditions that in the opinion of the investigator preclude the subject from appropriate consent or adherence to the protocol required follow-up exams

36. Pregnancy or intent to become pregnant prior to completion of all protocol follow-up requirements

37. Anatomical exclusion criteria (ANY of the following):

    1. Congenital bicuspid, unicuspid or quadricuspid aortic valve verified by echocardiography or CCT core laboratory
    2. Native aortic annulus perimeter <66 mm or >90 mm per the core laboratory reading of baseline cardiac CT imaging
    3. Iliofemoral arteries with vessel characteristics unsuitable for sheath passage (e.g., calcification, tortuosity) as determined by the case review board (CRB)
    4. Significant abdominal or thoracic aortic disease (such as porcelain aorta, aneurysm, severe calcification, aortic coarctation) that would preclude safe passage of the delivery system or cannulation and aortotomy for SAVR
    5. According to the CRB, a combination of aortic root angulation (angle between the plane of the aortic valve annulus and horizontal plane/vertebrae), sinus size, and straight length of the aorta that will not allow safe device delivery and THV deployment
    6. Sinus of Valsalva anatomy that would prevent adequate coronary perfusion after valve implantation

38. According to core laboratory evaluation, severe aortic stenosis

39. Uncorrected hypertrophic obstructive cardiomyopathy

40. Echocardiographic or Multi-slice CT (MSCT) evidence of untreated intracardiac mass or vegetation

41. Left ventricular thrombus

42. Left atrial thrombus without continuous appropriate anticoagulation within 90 days of the study procedure

43. Complex coronary artery disease:

    1. Unprotected left main coronary artery disease ≥50%
    2. Syntax score >32 (in the absence of prior revascularization)
    3. Heart Team determines that optimal revascularization cannot be adequately performed with EITHER CABG at the time of SAVR OR PCI at least 30 days prior to THV implant.