REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve SystEm

Study Overview
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Brief Summary
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This is a prospective, single-arm feasibility study designed to assess the acute safety and performance of the Lotus Valve System for transcatheter aortic valve replacement in symptomatic patients with calcified aortic valve stenosis and who are at high risk for surgical intervention.

Detailed Description
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The incidence of aortic stenosis is increasing due to the aging of the world-wide population and the lack of drug therapies to prevent, halt, or effectively slow the stenotic process. Transcatheter aortic valve replacement has become a viable alternative for treatment of severe symptomatic aortic stenosis in selected patients who are unsuitable candidates for surgical valve replacement. The Lotus Valve System is designed to enable precise placement and minimize or eliminate the paravalvular regurgitation and associated adverse events seen with earlier generation devices. The REPRISE I study assesses acute safety and performance.

Official Title
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REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve SystEm

Conditions
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Aortic Valve Stenosis, Aortic Valve Calcification, Aortic Valve Disease

Intervention / Treatment
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* Device: Lotus Valve System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be at least 70 years of age or older, and meets all of the criteria below. Patient has documented calcified native aortic valve stenosis, defined with an initial aortic valve area (AVA) of <1.0 cm2 (or AVA index of <0.6 cm2/m2), and a mean pressure gradient >40 mmHg or a jet velocity >4 m/s, as measured by echocardiography. The patient is considered at high risk for surgical aortic valve replacement with an STS (Society of Thoracic Surgeons) score ≥8% or a EuroSCORE ≥20%, or documented multidisciplinary heart team agreement that the patient is at high risk for surgery due to frailty and/or coexisting comorbidities. Symptomatic aortic valve stenosis with New York Heart Association (NYHA) Functional Class ≥ II. Patient has a documented aortic annulus size between 19 and 22 mm (able to accommodate the 23 mm Lotus™ Valve). Pre-procedure measurement by transthoracic echocardiography (TTE) is required. Other imaging modalities (e.g., transesophageal echocardiography (TEE), CT scan) can be used in an adjunctive manner. Patient (or legal representative) understands the trial requirements and the treatment procedures, and provides written informed consent. Patient agrees and is capable of returning to the study hospital for all required scheduled follow up visits. Exclusion Criteria: Patient has a congenital unicuspid or bicuspid aortic valve. Patient with an acute myocardial infarction (MI) within 30 days of the index procedure (defined as Q wave MI, or non-Q wave MI with total creatine kinase (CK) elevation ≥ twice normal in the presence of CK-MB elevation and/or troponin level elevation (WHO definition)). Patient has had a cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months, or has any permanent neurologic defect prior to study enrollment. Patient is on dialysis or has serum creatinine level >3.0 mg/dL. Patient has a pre-existing prosthetic heart valve (aortic or mitral) or a prosthetic ring in any position. Patient has >2+ mitral regurgitation or >2+ aortic regurgitation (ie., patient cannot have more than moderate mitral or aortic regurgitation). Moderate to severe pulmonary hypertension (PA systolic pressure >60 mm Hg) as assessed by transthoracic echocardiography. Patient has a need for emergency surgery for any reason. Patient has a history of endocarditis within 12 months of index procedure or evidence of an active systemic infection or sepsis. Patient has echocardiographic evidence of intra-cardiac mass, thrombus or vegetation. Patient has Hgb <9 g/dL, platelet count <100,000 cells/mm3 or >700,000 cells/mm3, and white blood cell (WBC) count <3,000 cells/mm3. Patient is receiving chronic (≥72 hours) anticoagulation therapy (e.g., heparin, warfarin) and who cannot tolerate concomitant therapy with aspirin and clopidogrel (patients who require chronic anticoagulation must be treated with either aspirin or clopidogrel). Patient has active peptic ulcer disease, gastrointestinal (GI) bleed within the past 3 months, other bleeding diathesis or coagulopathy or will refuse transfusions. Patient is contraindicated for transesophageal echocardiography (TEE). Patient has known hypersensitivity to contrast agents that cannot be adequately pre-medicated, or has known hypersensitivity to aspirin, all thienopyridines, heparin, nickel, titanium, or polyurethanes. Patient has a life expectancy of less than 12 months due to non-cardiac, co-morbid conditions based on the assessment of the investigator at the time of enrollment. Patient has other cardiac devices or hardware with which the study device will interfere with device placement (per physician judgment). Patient has hypertrophic obstructive cardiomyopathy. Patient has any therapeutic invasive cardiac procedure within 30 days prior to the index procedure. Untreated clinically significant coronary artery disease requiring revascularization. Patient has documented left ventricular ejection fraction (LVEF) <30%. Patient is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices. Patient has severe peripheral vascular disease (including aneurysm defined as maximal luminal diameter >5cm or with documented presence of thrombus, marked tortuosity, narrowing of the abdominal aorta, severe unfolding of the thoracic aorta or thick (>5mm), protruding or ulcerated atheroma in the aortic arch) or symptomatic carotid or vertebral disease. Patient has a femoral artery lumen of <6.0 mm or severe iliofemoral tortuosity or calcification that would prevent safe placement of the introducer sheath. Current problems with substance abuse (e.g. alcohol, cocaine, heroin, etc). Patient is participating in another investigational drug or device study that has not reached its primary endpoint. Patient has preexisting untreated conduction system disorders: Type II second-degree atrioventricular (AV) block, bifascicular or trifascicular block.

Ages Eligible for Study
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Minimum Age: 70 Years

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: Lotus Valve System<br>Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis | Device: Lotus Valve System<br>* The Lotus Valve System includes the Lotus Valve, a bovine tissue tri-leaflet bioprosthetic aortic valve, and the Lotus Delivery Catheter for guidance and placement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Procedural Success | Clinical procedural success defined as successful implantation of a Lotus Valve System (Device Success) without in-hospital Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) through discharge or 7 days post-procedure, whichever comes first. | Discharge or 7 days post-procedure, whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Performance Endpoint-Repositioning | Successful repositioning of the Lotus Valve System if repositioning is attempted | procedure | 
| Device Performance Endpoint-Valve Retrieval, if Attempted | Successful retrieval of the Lotus Valve System if retrieval is attempted | procedure | 
| Central Aortic Regurgitation | As determined by echocardiography | Discharge or 7 days post-procedure, whichever comes first | 
| Paravalvular Aortic Regurgitation | As determined by echocardiography | Discharge or 7 days post-procedure, whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic Valve Stenosis, Transcatheter Aortic Valve Replacement