REPRISE Next Generation Delivery System

Study Overview
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Brief Summary
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To confirm the acute performance and safety of the Lotus™ Valve with the Next Generation Delivery System for transcatheter aortic valve replacement (TAVR) in symptomatic patients with severe calcific aortic stenosis who are considered high risk for surgical valve replacement.

Detailed Description
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This clinical study is a prospective single-arm study designed to demonstrate that the acute performance and safety of the LOTUS Edge Valve System when used with the iSleeve Introducer Set or current Lotus Introducer Set are consistent with the results of the Lotus Valve System used in the REPRISE II study, when delivered and deployed in symptomatic subjects who have severe calcific aortic valve stenosis and who are at high risk for surgical aortic valve replacement (SAVR).

Official Title
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REPRISE NGDS: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of LotuS™ ValvE With the Next Generation Delivery System

Conditions
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Aortic Stenosis

Intervention / Treatment
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* Device: Lotus Valve and LOTUS Edge Valve System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥70 years of age Subject has documented calcific native aortic valve stenosis with an initial aortic valve area (AVA) of ≤1.0 cm2 (or AVA index of ≤0.6 cm2/m2) and either a mean pressure gradient ≥40 mm Hg or a jet velocity ≥4 m/s, as measured by echocardiography. Subject has a documented aortic annulus size between ≥20 and ≤27.5 mm based on pre-procedure diagnostic imaging Subject has symptomatic aortic valve stenosis with NYHA Functional Class ≥ II. Subject is considered high risk for surgical valve replacement based on at least one of the following: Society of Thoracic Surgeons (STS) score ≥8%, and/or Agreement by the heart team (which must include an in-person evaluation by an experienced cardiac surgeon) that subject is at high operative risk of serious morbidity or mortality with surgical valve replacement. Heart team (which must include an experienced cardiac surgeon) assessment that the subject is likely to benefit from valve replacement Subject (or legal representative) understands the study requirements and the treatment procedures, and provides written informed consent. Subject, family member and/or legal representative agree(s) and subject is capable of returning to the study hospital for all required scheduled follow up visits. Exclusion Criteria: Subject has a congenital unicuspid or bicuspid aortic valve. Subject with an acute myocardial infarction within 30 days of the index procedure (defined as Q-wave MI or non-Q-wave MI with total CK elevation ≥ twice normal in the presence of creatine kinase-myoglobin band (CK-MB) elevation and/or troponin level elevation). Subject has had a cerebrovascular accident or transient ischemic attack within the past 6 months, or has any permanent neurologic defect prior to study enrollment. Subject is on dialysis or has serum creatinine level >3.0 mg/dL or 265 µml/L. Subject has a pre-existing prosthetic heart valve (aortic or mitral) or a prosthetic ring in any position. Subject has ≥3+ mitral regurgitation, ≥3+ aortic regurgitation or ≥3+ tricuspid regurgitation (i.e., subject cannot have more than moderate mitral, aortic or tricuspid regurgitation). Subject has a need for emergency surgery for any reason. Subject has a history of endocarditis within 12 months of index procedure or evidence of an active systemic infection or sepsis. Subject has echocardiographic evidence of intra-cardiac mass, thrombus or vegetation. Subject has Hgb <9 g/dL, platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <1,000 cells/mm3. Subject is receiving chronic (≥72 hours) anticoagulation therapy (warfarin), and cannot tolerate concomitant therapy with aspirin or clopidogrel (subjects who require chronic anticoagulation must additionally be able to be treated with either aspirin or clopidogrel).* Subject has active peptic ulcer disease or gastrointestinal bleed within the past 3 months, other bleeding diathesis or coagulopathy or will refuse transfusions. Subject 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. Subject 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. Subject has hypertrophic obstructive cardiomyopathy. Subject has any therapeutic invasive cardiac procedure within 30 days prior to the index procedure (except for balloon aortic valvuloplasty and pacemaker implantation which are allowed). Subject has untreated coronary artery disease, which in the opinion of the treating physician, is clinically significant and requires revascularization. Subject has documented left ventricular ejection fraction <30%. Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices. Subject has severe peripheral vascular disease (including aneurysm defined as maximal luminal diameter >5 cm or with documented presence of thrombus, marked tortuosity, narrowing of the abdominal aorta, severe unfolding of the thoracic aorta or thick [>5 mm] protruding or ulcerated atheroma in the aortic arch) or symptomatic carotid or vertebral disease. Femoral artery lumen of <6.0 mm for subjects requiring 23 mm valve size or <6.5 mm for subjects requiring 27 mm valve size, or severe iliofemoral tortuosity or calcification that would prevent safe placement of the introducer sheath. Current problems with substance abuse (e.g., alcohol, etc.). Subject is participating in another investigational drug or device study that has not reached its primary endpoint. Subject has untreated conduction system disorder (e.g., Type II second degree atrioventricular block) that in the opinion of the treating physician is clinically significant and requires a pacemaker implantation.

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 and LOTUS Edge Valve System<br>Transcatheter aortic valve replacement (TAVR) with Lotus Valve System with the Next Generation Delivery System and LOTUS Edge Valve System | Device: Lotus Valve and LOTUS Edge Valve System<br>* Transcatheter aortic valve replacement (TAVR) with the Lotus Valve System with the Next Generation Delivery System and LOTUS Edge Valve System, with either the Lotus Introducer or iSleeve Introducer Sets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical Success | Defined as successful vascular access, delivery, and deployment of the Lotus Valve; successful retrieval with the Lotus Next Generation delivery system; and correct positioning of a single Lotus Valve in the proper anatomical location (reported as percent of subjects implanted with a Lotus Valve). Reported as percent of subjects. | Immediately post-procedure (patient discharged from operative room) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful repositioning of the study valve if repositioning is attempted | Reported as percent of subjects | Immediately post-procedure (patient discharged from operative room) | 
| Successful retrieval of the study valve if retrieval is attempted | Reported as percent of subjects | Immediately post-procedure (patient discharged from operative room) | 
| Severe or moderate paravalvular aortic regurgitation as measured by echocardiography and assessed by an independent core laboratory | Reported as percent of subjects | At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Mild, trace/trivial, or no paravalvular aortic regurgitation as measured by echocardiography and assessed by an independent core laboratory | Reported as percent of subjects | At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Mean aortic valve pressure gradient as measured by echocardiography and assessed by an independent core laboratory | Reported as mean ± standard deviation; mmHg | At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Effective orifice area as measured by echocardiography and assessed by an independent core laboratory | Reported as mean ± standard deviation; cm2 | At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Peak aortic valve pressure gradient as measured by echocardiography and assessed by an independent core laboratory | Reported as mean ± standard deviation; mmHg | At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Peak aortic velocity as measured by echocardiography and assessed by an independent core laboratory | Reported as mean ± standard deviation; m/sec | At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Mortality: all-cause, cardiovascular, and non-cardiovascular | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Stroke: disabling and non-disabling | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Myocardial infarction (MI): periprocedural (≤72 hours post index procedure) and spontaneous (>72 hours post index procedure) | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Bleeding: life-threatening (or disabling) and major | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Acute kidney injury based on the Acute Kidney Injury Network (AKIN) System Stage 3 (including renal replacement therapy) or Stage 2 | Reported as percent of subjects | ≤7 days post index procedure | 
| Major vascular complications major | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Repeat procedure for valve-related dysfunction (surgical or interventional therapy) | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Hospitalization for valve-related symptoms or worsening congestive heart failure (NYHA class III or IV) | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| New permanent pacemaker implantation resulting from new or worsened conduction disturbances | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| New onset of atrial fibrillation or atrial flutter | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Coronary obstruction | Reported as percent of subjects | ≤72 hours post index procedure | 
| Ventricular septal perforation | Reported as percent of subjects | ≤72 hours post index procedure | 
| Mitral apparatus damage | Reported as percent of subjects | ≤72 hours post index procedure | 
| Cardiac tamponade | Reported as percent of subjects | ≤72 hours post index procedure | 
| Prosthetic aortic valve malpositioning, including valve migration, valve embolization, or ectopic valve deployment | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Transcatheter aortic valve (TAV)-in-TAV deployment | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Prosthetic aortic valve thrombosis | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Prosthetic aortic valve endocarditis | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Neurological status per modified Rankin Scale score | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Neurological status per National Institutes of Health Stroke Scale | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure | 
| Functional Improvement from baseline per NYHA functional classification | Reported as percent of subjects | At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure |