Investigation of the NVT ALLEGRA Plus THV System in Patients With Severe Aortic Stenosis or Failed Surgical Aortic Bioprosthesis

Study Overview
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Brief Summary
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The EMPIRE II study evaluates the safety and performance of the entire ALLEGRA THV System. The primary safety endpoint is composite of all-cause mortality or stroke rates at 12 months. And the primary performance endpoint is device success at 7 days. Based on the outcomes of a study with a similar device and considering a drop-out rate of 5%, 177 patients need to be enrolled in the study.

Official Title
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InvEstigation of the Safety and Performance of the NVT ALLEGRA Plus THV SysteM in Patients With Severe aortIc Stenosis or Failed suRgical Aortic bioprosthEsis

Conditions
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Transcatheter Aortic Valve Implantation

Intervention / Treatment
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* Device: (ALLEGRA Plus Transcatheter Heart Valve) TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic severe calcific stenosis of a native aortic valve with an AVA ≤1.0 cm2 (or AVA index ≤0.6 cm2/m2), AND mean aortic pressure gradient ≥ 40mmHg OR maximal transaortic velocity ≥4.0m/s OR Doppler velocity index ≤0.25 on site-reported echocardiography OR symptomatic patients with degeneration of a surgical bioprosthetic valve (stenosis +/- insufficiency) on site-reported echocardiography Local multi-disciplinary Heart Team and Central Screening Committee (CSC) agree on indication and eligibility for TAVI Age ≥18 years Patient has signed the Patient Informed Consent Form Patient is willing and able to comply with requirements of the study, including all follow-up visits Exclusion Criteria: Patient will not be included if ANY one of the following conditions exists: General: Mean aortic annulus diameter as measured by pre-procedural CT or internal diameter of the bioprosthesis is <16.5 mm or >27 mm Echocardiographic evidence of intracardiac thrombus or vegetation (site-reported) Significant disease of the aorta that would preclude safe advancement of the ALLEGRA Plus THV System Severe ilio-femoral vessel disease that would preclude safe placement of an 18 Fr introducer sheath or make endovascular access impossible Porcelain aorta Severe left ventricular dysfunction with ejection fraction (EF) <20% (site-reported) Evidence of active endocarditis or other acute infections Renal failure requiring continuous renal replacement therapy Untreated clinically significant coronary artery disease requiring revascularization Any percutaneous interventional procedure (e.g. PCI with stenting) within 14 days prior of the index procedure Acute MI ≤30 days prior to the index procedure Symptomatic carotid or vertebral artery disease requiring intervention or carotid/vertebral intervention within the preceding 45 days Cerebrovascular accident (CVA) or transient ischemic attack (TIA) ≤6 months or prior CVA with moderate or severe disability (e.g. modified Rankin scale score >2) History of bleeding diathesis or coagulopathy; acute blood dyscrasias as defined: thrombocytopenia (platelets <80,000/µl), acute anemia (hemoglobin <10 g/dl), leukopenia (WBC <3000/ µl) Active peptic ulcer or gastrointestinal (GI) bleeding ≤3 months Severe (greater than 3+) mitral insufficiency (site-reported) Uncontrolled atrial fibrillation Required emergency surgery for any reason Known hypersensitivity to contrast media, which cannot be adequately pre-medicated or contraindication to anticoagulant or anti-platelet medication or to nitinol alloy or to bovine tissue Life expectancy ≤12 months due to other medical illness Currently participating in another investigational drug or device study Hypertrophic obstructive cardiomyopathy Pregnancy or intend to become pregnant during study participation Specific exclusions in patients with native aortic valve disease (site-reported): Unicuspid or bicuspid aortic valve Non-calcified aortic stenosis Identified risk of coronary occlusion due to Sinus of Valsalva anatomy and/or bulky calcified aortic valve leaflets in close proximity to coronary ostia Specific exclusions in patients with degenerated surgical bioprosthetic aortic valves (valve-in-valve) (site-reported): High risk of coronary occlusion Partially detached leaflets that may obstruct a coronary ostium

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis<br> | Device: (ALLEGRA Plus Transcatheter Heart Valve) TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis<br>* Implantation of the ALLEGRA Plus Transcatheter Heart Valve in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of all-cause mortality or stroke rates |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality rate |  | 7d, 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| Cardiovascular mortality rate |  | 7d, 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| Any stroke rate |  | 7d, 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| Transient ischemic attack rate |  | 7d, 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| Device success rate | Device success at 30 days (In-hospital may be used if 30-day data are not available): Technical success Freedom from mortality Freedom from surgery or intervention related to the device (excluding permanent pacemaker) or to a major vascular or access-related or cardiac structural complication Intended performance of the valve‡(mean gradient<20 mmHg, peakvelocity<3 m/s, Doppler velocity index ≥0.25, and less than moderate aortic regurgitation | 30 days | 
| Effective orifice area (EOA) as assessed by transthoracic echocardiogram (TTE) | as determined by an independent Echo Core Lab | 7d, 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| Transvalvular mean and peak pressure gradient as assessed by transthoracic echocardiogram (TTE) | as determined by an independent Echo Core Lab | 7d, 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| Transvalvular mean and peak pressure gradient as assessed by transthoracic | as determined by an independent Echo Core Lab | 7d, 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| NYHA classification |  | 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| Life-threatening/major bleeding (BARC 3b or more) |  | 7d,, 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| Major vascular complications according to VARC-3 |  | 7d,, 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| Early safety profile according to VARC-3 |  | 30 days | 
| Quality of life as assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) | Assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Patients are asked questions about physical limitation, symptom frequency, quality of life, and social limitation. Responses are given on a Likert scale that for each individual item is scored on a scale of 0-100 with higher scores indicating better health. | 30d, 6m, 12m, 2y, 3y, 4y, 5y | 
| New pacemaker implantation rate |  | 7d, 30d, 6m, 12m, 2y, 3y, 4y, 5y | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TAVI, Aortic valve stenosis, ALLEGRA Plus, IMPERIA, NVT