TranScatheter Aortic Valve RepLacement System US Feasibility Trial

Study Overview
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Brief Summary
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A study to assess the safety and effectiveness of the Direct Flow Medical aortic valve system. This is for people with severe aortic stenosis who are not well enough to undergo a surgical repair. The delivery of this device is done via the femoral artery.

Detailed Description
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The Direct Flow Medical Transcatheter Aortic Valve System is indicated for symptomatic patients who require replacement of their native aortic valve and have a predicted operative mortality or serious morbidity risk of equal or greater 50% at 30 days with surgical aortic valve replacement or are deemed unsuitable for surgery.

Official Title
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The Direct Flow Medical TranScatheter Aortic Valve RepLacement System US Feasibility Trial

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: Transcatheter aortic valve replacement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has severe senile degenerative aortic valve stenosis determined by resting or dobutamine stress echocardiogram and Doppler, or simultaneous pressure recordings at cardiac catheterization defined as: mean gradient >40 mmHg or peak jet velocity >4.0 m/s and an aortic valve area ≤0.8 cm2 or aortic valve area index ≤0.5 cm2/m2. The patient has moderate to severe symptoms from aortic valve stenosis (NYHA Functional Class ≥III). The patient must have a predicted risk of operative mortality or serious irreversible morbidity of >50% at 30 days, or be deemed not suitable for surgery for other reasons. This conclusion shall be based on consensus of one cardiologist and two cardiac surgeons at the investigational site after careful consideration of the patient's STS risk score and co-morbidities, and after at least one of the surgeons participating in the decision has personally examined the patient. The patient been informed of the nature of the study, agrees to its provisions, is willing to comply with protocol-specified follow-up evaluations and has provided written informed consent, approved by the appropriate IRB. Exclusion Criteria Left ventricular ejection fraction (LVEF) <20% determined by resting echocardiogram Patients with an acute MI within 30 days preceding the index procedure. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the study procedure Patients with impaired renal function (estimated Glomerular Filtration Rate [eGFR] <20cc/min, calculated from serum creatinine by the Cockcroft-Gault formula) Patients with a platelet count of <50,000 cells/mm³ or a WBC < 1000 cells/mm³ within 7 days prior to index procedure. Patients with a history of bleeding diathesis or coagulopathy or patients in whom anti-platelet and/or anticoagulant therapy is contraindicated, or who will refuse transfusion. Patients who have received any organ transplant or are on a waiting list for any organ transplant. Patients with known other medical illness (e.g. carcinomas, chronic liver disease, chronic renal disease or chronic end stage pulmonary disease) or known history of substance abuse that may cause non-compliance with the protocol, confound the data interpretation or is associated with a life expectancy of less than one year, or expectation that patient will not improve despite treatment of aortic stenosis. Patients with known hypersensitivity or contraindication to aspirin, heparin, clopidogrel/ticlopidine, and/or contrast sensitivity that cannot be adequately pre-medicated. Patients with a history of a stroke or transient ischemic attack (TIA) within the prior 6 months. Patients with an active gastrointestinal (GI) bleeding within the prior 6 months. Patients presenting with hemodynamic instability or cardiogenic shock defined by low cardiac output, vasopressor dependence, or mechanical hemodynamic support. Patients who have a planned treatment with any other investigational device or procedure during the study period, or who are currently participating in an investigational drug or another device trial Any planned surgical, percutaneous coronary or peripheral procedure to be performed prior to the 30 day follow-up from the TAVR procedure. Untreated clinically significant coronary artery disease requiring revascularization Trans-esophageal echocardiography (TEE) is contraindicated Active endocarditis or sepsis within 6 months prior to the study procedure 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) Congenital bicuspid or unicuspid valve determined by echocardiography Prior aortic or mitral valve surgery or pre-existing prosthetic heart valve in any position Native valve annulus diameter is <19mm or >26mm determined by the screening CT scan Extreme asymmetrical calcification of the native aortic valve determined by the screening CT scan Echocardiographic evidence of intra-cardiac mass, thrombus, vegetation, or spontaneous echo contrast in the left atrium >3+ aortic regurgitation, mitral regurgitation or tricuspid regurgitation Moderate to severe mitral stenosis Thoracic aortic aneurysm (TAA) or abdominal aortic aneurysm (AAA) >5.0 cm Presence of an endovascular stent graft for treatment of AAA or TAA 28 Hypertrophic obstructive cardiomyopathy 29. Patients with severe peripheral arterial disease that precludes sheath vascular access (e.g. luminal diameter less than 6.5 mm, severe obstructive calcification or severe tortuosity)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm feasibility study<br>Prospective, multi-center, single arm feasibility study. Subjects will include patients with severe aortic valve stenosis who require replacement of their native aortic valve. The intervention is transcatheter aortic valve replacement. | Device: Transcatheter aortic valve replacement<br>* Direct Flow Medical Transcatheter Aortic Valve System is indicated for use in aortic stenosis for patients at extreme surgical risk for aortic valve replacement.<br>* Other names: TAVR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from all cause mortality/Device success | Absence of procedural mortality AND correct positioning of a single prosthetic heart valve into the proper anatomic location AND Intended performance of the prosthetic heart valve (no prosthesis-patient mismatch and mean aortic valve gradient less than 20 mmHg or peak velocity less than 3m/s, AND no moderate or severe prosthetic valve regurgitation. | 6 months post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Safety | Early Safety: as a composite of All-cause mortality All stroke (disabling and non-disabling) Life-threatening bleeding Acute Kidney Injury - Stage 2 or 3 (including renal replacement therapy) Coronary artery obstruction requiring intervention Major vascular complications Valve-related dysfunction requiring repeat procedure (BAV, TAVR, or SAVR) | 30 Days | 
| Clinical Efficacy | Clinical Efficacy will be evaluated as a composite of: All-cause mortality All stroke (disabling and non-disabling) Hospitalization for valve-related symptoms or worsening congestive heart failure† (including reporting of days hospitalized) NYHA Class III or IV Prosthetic heart valve dysfunction (mean aortic valve gradient ≥20 mm Hg, EOA ≤0.9-1.1 cm2‡ and/or DVI <0.35, AND/OR moderate or severe prosthetic valve regurgitation*) | 6 months,and annually at 1 to 5 years | 
| Time-related Valve Safety | Time-related valve safety will be evaluated as a composite of: Structural valve deterioration: Valve-related dysfunction (mean aortic valve gradient (mean aortic valve gradient ≥20 mm Hg, EOA ≤0.9-1.1 cm2[Depending on body surface area] and/or DVI <0.35, AND/OR moderate or severe prosthetic valve regurgitation [VARC defined]) Requiring repeat procedure (TAVR or SAVR) Prosthetic valve endocarditis Prosthetic valve thrombosis Thromboembolic events (e.g., stroke) VARC bleeding, unless clearly unrelated to valve therapy (e.g., trauma) | 30 days, 6 months and annually at 1 to 5 years | 
| Clinical Endpoints | Individual Endpoints All-cause mortality Cardiovascular mortality Non-cardiovascular mortality Myocardial Infarction Peri-procedural MI (<72 hours after the index procedure) Spontaneous MI (>72 hours after the index procedure) Neurological Events Stroke Ischemic stroke Hemorrhagic stroke Undetermined Disabling Stroke Non-disabling stroke Transient ischemic attack Bleeding Complications Life-threatening or disabling bleeding Major bleeding Minor bleeding Acute Kidney Injury (AKIN Classification) Stage 1 acute kidney injury Stage 2 acute kidney injury Stage 3 acute kidney injury Vascular Complications Major vascular complications Minor vascular complications Percutaneous closure device failure Prosthetic Valve Dysfunction Prosthetic Aortic Valve Stenosis Prosthesis-Patient Mismatch Prosthetic Aortic Valve Regurgitation | 30 days, 6 months and annually at 1 to 5 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pathological constriction; restricted outflow, stenosis