Investigation of the ALLEGRA THV System With a New Delivery System in Patients With Aortic Stenosis or Failed Surgical Bioprosthesis

Study Overview
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Brief Summary
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The EMPIRE study confirms the technical performance of the new IMPERIA Delivery System and evaluates the safety and efficacy of the entire ALLEGRA THV System. The primary endpoint is device success rate at 7 days (discharge from index procedure or 7 days post implant, whichever comes first), as defined by VARC 2. Based on the outcomes of a study with a similar device and considering a drop-out rate of 5%, 107 patients need to be enrolled in the study.

Official Title
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Investigation of the Safety and Performance of the NVT ALLEGRA THV System With a New Delivery System in Patients With Severe Calcified Aortic Stenosis or Failed Surgical Aortic Bioprosthesis

Conditions
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Transcatheter Aortic Valve Implantation

Intervention / Treatment
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* Device: (ALLEGRA 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: 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 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 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 Predominant aortic regurgitation > grade 3 Distance between native aortic valve basal plane and the orifice of the lowest coronary artery <8 mm Specific exclusions in patients with degenerated surgical bioprosthetic aortic valves (valve-in-valve) (site-reported): Low position of the coronary ostia, especially in combination with shallow sinuses (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: treatment<br>TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis | Device: (ALLEGRA Transcatheter Heart Valve) TAVI in severe calcified aortic stenosis or in failed surgical aortic bioprosthesis<br>* Implantation of the ALLEGRA Transcatheter Heart Valve in failing surgical bioprosthesis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device success at 7 days | Absence of procedural mortality AND Correct positioning of a single device in the proper anatomical location (site-reported) AND Intended performance of the prosthetic heart valve (as determined by an independent Echo Core Lab at discharge from index procedure or 7 days post implant, whichever comes first) Indexed Effective Orifice Area (iEOA) > 0.85 cm2/m2 for BMI < 30kg/m2 and iEOA > 0.70 cm2/m2 for BMI ≥ 30kg/m2 Mean aortic valve gradient <20 mmHg or peak velocity <3 m/s No moderate or severe prosthetic valve regurgitation | 7 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality |  | up to 12 months | 
| Cardiovascular mortality |  | up to 12 months | 
| All stroke |  | up to 12 months | 
| TIA |  | up to 12 months | 
| Procedural success | Successful vascular access, delivery and deployment of the ALLEGRA THV including re- positioning if required and successful retrieval of the IMPERIA Delivery System (site- reported) Correct position of the ALLEGRA THV (site-reported) Only one ALLEGRA THV implanted in proper anatomical position (site-reported) | assessed immediately after the procedure | 
| Effective orifice area (EOA) as assessed by transthoracic echocardiogram (TTE) |  | up to 12 months | 
| Transvalvular mean and peak pressure gradient as assessed by transthoracic echocardiogram (TTE) |  | up to 12 months | 
| Trans- and paravalvular regurgitation as assessed by transthoracic echocardiogram (TTE) |  | up to 12 months | 
| NYHA classification |  | 30 days, 6 months, and 12 months | 
| Early safety | 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 complication Valve-related dysfunction requiring repeat procedure (BAV, TAVI, or SAVR) | up to 30 days | 
| Time-related valve safety | Structural valve deterioration Valve-related dysfunction (mean aortic valve gradient 20 mmHg, EOA ≤0.9-1.1 cm2c and/or DVI <0.35 m/s, AND/OR moderate or severe prosthetic valve regurgitation) Requiring repeat procedure (TAVI or SAVR) Prosthetic valve endocarditis Prosthetic valve thrombosis Thrombo-embolic events (e.g. stroke) VARC bleeding, unless clearly unrelated to valve therapy (e.g. trauma) | up to 12 months | 
| 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. | up to 12 months | 
| New pacemaker implantation |  | up to 12 months | 
| Delivery system related AEs |  | discharge from index procedure or 7 days post implant, whichever comes first | 

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