REPRISE IV: LOTUS Edge Valve System in Intermediate Surgical Risk Subjects

Study Overview
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Brief Summary
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REPRISE IV: REpositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of LOTUS Edge Valve System in IntermediatE Surgical Risk Subjects

Detailed Description
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To evaluate safety and effectiveness of the LOTUS Edge™ Valve System when used with the Lotus™ or iSleeve™ Introducer Sets for transcatheter aortic valve replacement (TAVR) in symptomatic subjects with severe aortic stenosis who are considered at intermediate risk for surgical valve replacement including those who have a bicuspid native valve.

Official Title
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REPRISE IV: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of LOTUS Edge Valve System in IntermediatE Surgical Risk Subjects

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: LOTUS Edge Valve System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has documented severe aortic stenosis defined as initial aortic valve area (AVA) ≤1.0 cm2 (or AVA index ≤0.6 cm2/m2) AND a mean pressure gradient ≥40 mm Hg OR maximal aortic valve velocity ≥4.0 m/s OR Doppler velocity index ≤0.25 as measured by echocardiography and/or invasive hemodynamics. Note: In cases of low flow, low gradient aortic stenosis with left ventricular dysfunction (ejection fraction <50%), dobutamine can be used to assess the grade of aortic stenosis (maximum dobutamine dose of 20 mcg/kg/min recommended)c; the subject may be enrolled if echocardiographic criteria are met with this augmentation. (IC1) A subject in the Bicuspid Aortic Valve Nested Registry cohort must have a documented Sievers Type 0 or Sievers Type 1 bicuspid aortic valve based on computed tomography (CT) assessment and confirmed by the CT core lab with hemodynamic parameters that meet the criteria in IC1. Subject has a documented aortic annulus size of ≥20 mm and ≤27 mm based on the center's assessment of pre-procedure diagnostic imaging (and confirmed by the Case Review Committee [CRC]). Subject has symptomatic aortic valve stenosis per IC1 definition above with New York Heart Association (NYHA) Functional Class ≥ II. Heart team (which must include an experienced cardiac interventionalist and an experienced cardiac surgeon) agrees that the subject is at intermediate risk of operative mortality (≥3% and <8% at 30 days based on the Society of Thoracic Surgeons [STS] risk score and other clinical comorbidities unmeasured by the risk calculator) and TAVR is appropriate. Note: Risk of operative mortality must be assessed via an in-person evaluation by a center cardiac surgeon and must be confirmed by the CRC (which must include an experienced cardiac surgeon). Heart team agrees that the subject is likely to benefit from valve replacement. IC7. Subject (or legal representative) has been informed of 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. Subject is expected to be able to take the protocol-required adjunctive pharmacologic therapy. Exclusion Criteria: Subject has a unicuspid or bicuspid aortic valve (not applicable to subjects in the Bicuspid Nested Registry cohort). Subjects in the Bicuspid Nested Registry cohort will have a documented Sievers Type 0 or Sievers Type 1 bicuspid aortic valve based on CT assessment and confirmed by the CT core lab. Subjects are not eligible for inclusion in the Bicuspid Nested Registry cohort if the maximum diameter of the ascending aorta is >45 mm or if the subject has another indication for aortic root replacement. Subjects with a Sievers Type 2 bicuspid valve are not eligible for enrollment in any study cohort. Subject has had an acute myocardial infarction (MI) within 30 days prior to 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 creatine kinase-myoglobin band (CK-MB) elevation and/or troponin elevation). Subject has had a cerebrovascular accident or transient ischemic attack clinically confirmed by a neurologist or neuroimaging within the past 6 months prior to study enrollment. Subject is on renal replacement therapy or has Glomerular Filtration Rate (GFR) <20 (based on hospital preferred method). See AEC1 below if subject is in the CT Imaging Substudy. Subject has a pre-existing prosthetic aortic or mitral valve. Subject has severe (4+) aortic, tricuspid, or mitral regurgitation. Subject has moderate to severe mitral stenosis (mitral valve area ≤1.5 cm2 and diastolic pressure half-time ≥150 ms, Stage C or Dc). Subject has a need for emergency surgery for any reason. Subject has a history of endocarditis within 6 months of index procedure or evidence of an active systemic infection or sepsis. Subject has echocardiographic evidence of new intra-cardiac vegetation or intraventricular or paravalvular thrombus requiring intervention. Subject has platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <1,000 cells/mm3. Subject will refuse transfusions or has had a gastrointestinal bleed requiring hospitalization or transfusion within the past 3 months, or has other clinically significant bleeding diathesis or coagulopathy that would preclude treatment with required antiplatelet regimen. Subject has known hypersensitivity to contrast agents that cannot be adequately pre-medicated, or has known hypersensitivity to aspirin, all P2Y12 inhibitors, heparin, nickel, tantalum, titanium, or polyurethanes. Subject has a life expectancy of less than 24 months due to non-cardiac, comorbid conditions based on the assessment of the investigator at the time of enrollment. Subject has hypertrophic cardiomyopathy. Subject has any therapeutic invasive cardiac or vascular procedure within 30 days prior to the index procedure (except for balloon aortic valvuloplasty or pacemaker or implantable cardioverter defibrillator implantation, which are allowed). Subject has multivessel coronary artery disease with a Syntax score >22, and/or an unprotected left main coronary artery. Subject has severe left ventricular dysfunction with ejection fraction <20%. Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices. Subject has arterial access that is not acceptable for the study device delivery system as defined in the device Instructions For Use. Subject has severe vascular disease that would preclude safe access (e.g., aneurysm with thrombus that cannot be crossed safely; marked tortuosity; significant narrowing of the abdominal aorta; severe unfolding of the thoracic aorta; or thick, protruding, ulcerated atheroma in the aortic arch). Subject has current problems with substance abuse (e.g., alcohol, etc.) that may interfere with the subject's participation in this study. 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. Enrollment is permissible after permanent pacemaker implantation. Subject has severe incapacitating dementia.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Evaluation of Lotus Edge to treat patients with aortic stenosis. A single intervention is being evaluated in 3 study arms, the roll-in, main and bicuspid cohorts.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Main Cohort<br>Transcatheter Aortic Valve Replacement (TAVR) with the LOTUS Edge Valve System | Device: LOTUS Edge Valve System<br>* TAVR with the LOTUS Edge Valve System<br>|
| Experimental: Roll-In Cohort<br>Transcatheter Aortic Valve Replacement (TAVR) with the LOTUS Edge Valve System | Device: LOTUS Edge Valve System<br>* TAVR with the LOTUS Edge Valve System<br>|
| Experimental: Bicuspid Cohort<br>Transcatheter Aortic Valve Replacement (TAVR) with the LOTUS Edge Valve System | Device: LOTUS Edge Valve System<br>* TAVR with the LOTUS Edge Valve System<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of All-cause Mortality and All Stroke. | Pre-specified primary outcome measure in the protocol for the Main Cohort only. Critical safety events that are observed in the elderly population undergoing TAVR; assessments recommended by Valve Academic Research Consortium (VARC) | 1 year post index procedure and device implantation |