j-valve transfemoral pivotal study

Conditions: Aortic Valve Regurgitation; Aortic Valve Disease Mixed

Summary: the primary objective of this study is to assess the safety and efficacy of the j-valve transfemoral (tf) system in patients with symptomatic, severe (grade 3 or 4), native aortic valve regurgitation (ar) and ar-dominant mixed aortic valve disease, who are judged by a multi-disciplinary heart team to be at high risk for open surgical aortic valve replacement (savr). a cardiac magnetic resonance (cmr) sub-study will examine if intervention for ar translates to improved ventricular remodeling, the impact of lv remodeling on clinical outcomes and quality of life, as well as volumetric and myocardial differences between genders.

this is a prospective, single arm, multi-center, interventional pivotal study that will enroll up to 194 subjects in up to 35 investigational sites, predominantly in the united states and up to 6 in canada, europe, and japan. of the 194 subjects, the cmr imaging sub-study will include up to 75 subjects with severe ar already confirmed by tte. additionally, up to 40 roll-in subjects may be treated to enable clinical experience and exposure to the device while allowing a reasonable learning curve. the subjects will then be followed 5-years post-procedure of the j-valve tf system.

Eligibility criteria:
inclusion criteria: 1. symptomatic according to new york heart association (nyha) functional class (fc) ii or higher 2. severe ar, defined as follows, as assessed by imaging core laboratory: a. severe ar by transthoracic echocardiography (tte) (grade 3 or 4) b. or, if indeterminate ar, by tte, any one of the following: i. cardiac magnetic resonance imaging (cmr)-derived aortic regurgitant fraction (rf) ≥43% ii. cmr-derived rf ≥33% + left ventricular dilation (left ventricular end diastolic volume index (lvedvi) \>105 ml/m\^2 for men or lvedvi \>96 ml/m\^2 for women) iii. cmr-derived rf ≥33% + lv ejection fraction (lvef) ≤55% or left-ventricular end-systolic volume index (lvesvi) ≥43ml/m\^2; iv. severe ar by transesophageal echocardiography (tee) (grade 3 or 4) 3. patient is judged by a multi-disciplinary heart team to be at high risk for surgery 4. patient has suitable anatomy to accommodate the insertion, delivery, and deployment of the study valve system 5. patient or the patient's legal representative has provided written informed consent and agrees to comply with all required post-procedure follow-up visits at investigational site. exclusion criteria: 1. previous prosthetic aortic valve (bioprosthesis or mechanical) implant 2. aortic valve stenosis \> moderate 3. severe mitral valve or tricuspid valve regurgitation 4. severe mitral valve or tricuspid valve stenosis 5. active infection, including infective endocarditis 6. cardiac imaging evidence of cardiac mass, thrombus or vegetation 7. inability to tolerate or a condition precluding treatment with antithrombotic (antiplatelet, anticoagulant) therapy 8. renal insufficiency (egfr \<30 ml/min/1.73m\^2) or end stage renal disease requiring chronic dialysis 9. liver disease including cirrhosis (childs-pugh class b or c) 10. blood dyscrasias as defined: leukopenia (wbc \<3000 mm\^3), thrombocytopenia (platelet count \<50,000 cells/mm\^3), anemia (hemoglobin \<9 g/dl), history of bleeding diathesis or coagulopathy 11. known hypersensitivity or contraindication to aspirin, heparin, bivalirudin, clopidogrel, nitinol (nickel, titanium, aluminum) or sensitivity to contrast media, which cannot be adequately premedicated 12. left ventricular dysfunction with left ventricular ejection fraction (lvef) \<25% as measured by resting echocardiogram (or by cmr, when performed) 13. clinically significant untreated coronary artery disease requiring revascularization or anticipated coronary revascularization procedure within 12-months post index procedure 14. acute myocardial infarction within 30 days prior to index procedure 15. pci within 30 days prior to index procedure 16. carotid intervention within 6 weeks prior to index procedure or carotid artery disease requiring intervention 17. previous, or planned, other surgical or interventional procedures within 30 days before, during, or within 30 days after the index procedure 18. uncontrolled atrial fibrillation 19. severe right ventricular (rv) dysfunction 20. pulmonary hypertension (systolic pa pressure \>70mmhg or systolic pa pressure ≥2/3 of systemic systolic bp) 21. severe chronic obstructive pulmonary disease (copd) requiring chronic oral steroids or requiring continuous home o2 22. stroke (cva), transient ischemic attack (tia) or neurological signs and symptoms attributed to carotid or vertebrobasilar disease within 3 months prior to index procedure 23. cardiogenic shock defined as systolic blood pressure \<90 mmhg in addition to signs of tissue hypoperfusion or the need for vasopressors and/or mechanical hemodynamic support to maintain systolic blood pressure ≥90mmhg 24. patient requires mechanical circulatory support within 30 days prior to index procedure 25. estimated life expectancy of less than 24 months due to associated non-cardiac co-morbid conditions 26. pregnancy or intent to become pregnant prior to completion of all protocol follow-up requirements 27. participation in another investigational study that has not reached its primary endpoint 28. subject considered to be part of a vulnerable population anatomic exclusions: 1. ascending aortic diameter \>5 cm 2. aortic annulus perimeter \ 104 mm 3. inappropriate anatomy for femoral introduction and delivery of the study system 4. left ventricular end-diastolic diameter (lvedd) \>75 mm 5. congenital aortic valve disease including unicuspid, bicuspid, or quadricuspid aortic valve anatomy 6. congenital univentricle or other condition that, in the opinion of the investigator and/or consulting physician, may constitute an unwarranted surgical risk 7. excessive aortic valve prolapse that would preclude proper seating of the implant in the aortic annulus 8. abdominal/thoracic aortic aneurysm ≥4.0 cm 9. aorto-iliac disease requiring intervention to facilitate delivery of access sheath 10. excessive tortuosity of delivery system pathway, defined as severe tortuosity of multiple vessels including iliofemoral, thoracoabdominal aorta, aortic arch, or lv-aortic root angle \>80⁰

Keywords: j-valve transfemoral system transcatheter therapy transcatheter aortic valve replacement tavr transfemoral