Aortic Regurgitation, Aortic Valve Insufficiency, Aortic Insufficiency
Conditions
Brief summary
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)
Interventions
DEVICETranscatheter Aortic Valve Replacement (TAVR) using Trilogy THV System
Transcatheter Aortic Valve Replacement (TAVR) with Trilogy Device
DEVICESAVR
SAVR using commercially available surgical prosthetic valves.
Sponsors
JenaValve Technology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality | 12 months | all-cause mortality at 12 months |
| All stroke | 12 months | Number of patients that had stroke |
| unplanned cardiac rehospitalization | 12 months | Number of patients who had unplanned cardiac rehospitalization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of index hospitalization | pre-intervention/procedure surgery | comparing TAVR length of index hospitalization with SAVR |
| Echocardiographic effective orifice area | 30 days | comparing TAVR Echocardiographic effective orifice area with SAVR |
| Moderate or greater patient prosthesis mismatch as measured by echo | 30 days or immediately after the intervention/procedure | comparing TAVR moderate or greater patient prosthesis mismatched with SAVR |
| Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) | 30 days | comparing change in KCCQ-OS in TAVR with SAVR. the minimum and maximum values vary based on the questionnaire. Higher scores mean better outcome. |
| Atrial fibrillation | 30 days | comparing the onset atrial fibrillation in TAVR with SAVR |
| Cardiovascular rehospitalization | 30 days | comparing the number of cardiovascular rehospitalizations in TAVR with SAVR |
| Composite primary endpoints | 30 days | comparing the superiority of the composite primary endpoint and its components in TAVR with SAVR |
| Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) | 30 days | Freedom of Major Adverse Cardiovascular and Cerebrovascular Events |
Countries
United States
Contacts
CONTACTDuane Pinto, MD MPH
PRINCIPAL_INVESTIGATORVinod H Thourani, MD
Piedmont Heart Institute
PRINCIPAL_INVESTIGATORTorsten P Vahl, MD
Columbia University
PRINCIPAL_INVESTIGATORRaj Makkar, MD
Cedars-Sinai Medical Center
PRINCIPAL_INVESTIGATORHendrik Treede, MD
Department of Cardiovascular Surgery Johannes-Gutenberg University
Outcome results
None listed