VitaFlowTM II Transcatheter Aortic Valve System Study

Study Overview
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Brief Summary
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A prospective, single arm clinical investigation evaluating safety and effectiveness/performance of the Microport CardioFlow VitaFlowTM II - Transcatheter Aortic Valve System for the treatment of symptomatic severe aortic stenosis via transcatheter access in increased surgical risk patients

Detailed Description
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This is a prospective, multicenter, single arm and controlled clinical investigation compared to recent historical results. The purpose is to evaluate the safety, performance and efficacy of the VitaflowTM II Transcatheter Aortic Valve system. The entire system including valve system, delivery system and introducer system. We will implant the valve system into subjects and followed up them for 5 years after the procedure. This clinical trial will be conducted in 15 sites in Europe.

Official Title
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The VITALE Study Evaluating Safety and Effectiveness/Performance of the Microport CardioFlow VitaFlow II - Transcatheter Aortic Valve System

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: VitaFlow II Transcatheter Aortic Valve System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects of age > 18 years Subjects suffering from severe aortic valve stenosis, including bicuspid and tricuspid valves, defined as follows: High-gradient aortic stenosis (mean pressure gradient across aortic valve >40 mmHg or peak velocity ≥4.0 m/s. Subject has symptomatic valve stenosis presenting with NYHA ≥ Class II Subjects with a documented heart team agreement of increased surgical risk as described in the population ECG-gated multi-slice computed tomographic (MSCT) measurements determined an aortic annulus or supra-annular diameter ≥17 and ≤29mm. Findings of TTE, TEE and conventional aortography should be integrated in the anatomic assessment, when performed Patient deemed eligible by Centralised Case Review Committee (CRC) assessment recommends VitaFlow™ II Transcatheter Aortic Valve System implantation Subject can understand the purpose of the clinical investigation, has signed voluntary the informed consent form and is agreeing to the scheduled follow up requirements Exclusion Criteria: Arterial aorto-iliac-femoral axis unsuitable for transfemoral access as assessed by conventional angiography and/or multi-detector computed tomographic angiography (access vessel diameter incompatible with a 19 to 22F OD delivery system with integrated sheath or 21 to 24F OD sheath) Aortic root anatomy condition or lesion preventing implantation or access to the aortic valve Non-calcific acquired aortic stenosis Native unicuspid aortic valve or congenital aortic abnormality (except for bicuspid aortic valve) not permitting TAVI Previous implantation of heart valve in any position Severe aortic regurgitation (>3+) Severe mitral regurgitation (>3+) Severe tricuspid regurgitation (>3+) Severe left ventricular (LV) dysfunction (left ventricular ejection fraction < 30%) Echocardiographic evidence of intracardiac mass, thrombus or vegetation Multi-vessel coronary artery disease with a Syntax score or residual Syntax score > 22 and/or unprotected left main coronary artery. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support Untreated cardiac conduction disease in need of pacemaker implantation Uncontrolled atrial fibrillation (resting heart rate > 120bpm) Active and/or suspicion of endocarditis or ongoing sepsis Blood dyscrasias defined as: leukopenia (WBC<1000 mm3), thrombocytopenia (PLT<50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states Evidence of an acute myocardial infarction ≤ 1 month (30 days) before signing informed consent Any need for emergency surgery Recent (within 6 months of signing informed consent) cerebrovascular accident (CVA) or transient ischemic attack (TIA) Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days prior to signing informed consent Any active bleeding that precludes anticoagulation Liver failure (Child-C) End-stage renal disease requiring chronic dialysis or creatinine clearance < 20cc/min Pulmonary hypertension (systolic pressure >80mmHg) Severe chronic pulmonary disease (COPD) demonstrated by an expiratory volume (FEV1) < 750cc Refusal of blood transfusion A known hypersensitivity or contraindication to all anticoagulation/antiplatelet regimens (or inability to be anticoagulated for the index procedure), to nitinol, to dairy products, to polyethylene terephthalate (PET) or contrast media Any medical, social or psychological condition that in the opinion of the investigator precludes the subject from giving appropriate consent or adherence to the required follow up procedures Currently participating in another drug or device trial (excluding registries) for which the primary endpoint has not been assessed Estimated life expectancy of less than 12 months For female - pregnancy or intention to become pregnant prior to completion of all follow up procedures Inability to comply with the clinical investigation follow-up or other clinical investigation requirements

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: Single arm clinical investigation<br>Subjects in experimental group will be implanted the VitaFlow II Transcatheter Aortic Valve System. | Device: VitaFlow II Transcatheter Aortic Valve System<br>* VitaFlow II Transcatheter Aortic Valve System contains a Valve stent -VitaFlow Aortic Valve, a Delivery system-VitaFlow II Delivery System and a Introducer set<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of all-cause mortality at 12 months post implantation | all-cause mortality including cardiovascular and non-cardiovascular | 12 months post implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Composite of all-cause mortality and disabling stroke | defined as the ratio of all-cause dead and disabled subjects to total subjects at each time point | at 30 days, 6 months,12 months, 2, 3, 4 and 5 years post implantation | 
| Rate of stroke (disabling and non-disabling) | defined as the ratio of stroke subjects (disabling and non-disabling) to total subjects at each time point | at 30 days, 6 months,12 months, 2, 3, 4 and 5 years post-implantation | 
| Initial success | defined as absence of procedural mortality AND correct positioning of a single VitaFlowTM Aortic Valve into the proper anatomical location AND absence of patient / VitaFlowTM Aortic Valve mismatch AND mean aortic valve gradient less than (<) 20 mmHg or peak velocity less than (<) 3m/s, AND absence of moderate or severe prosthetic valve regurgitation | within 30 days post-implantation | 
| Recapture success rate (when attempted) | defined as VitaFlowTM Aortic Valve is fully re-sheathed into the VitaFlowTM II delivery system, as verified by fluoroscopy | at 1st day post-implantation | 
| Successful insertion | navigation and functioning of ALL features for the VitaFlowTM II delivery system, deployment and implantation of the VitaFlowTM aortic valve and subsequent retrieval of the VitaFlowTM II delivery system | at 1st day post-implantation | 
| Valve function | Evaluating valva function(including valve position, morphology, function and rate of valvular stenosis, valve regurgitation, orifice area and pressure gradient and paravalvular leakage) at each time point. | at 30 days, 6 and 12 months and 2, 3, 4, 5 years post-implantation | 
| Changes in quality of life KCCQ | an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. | at 30 days, 6 and 12 months and 2, 3, 4, 5 years post-implantation compared to baseline | 
| Changes in quality of life EQ-5D-5L | Use the questions and score system to evaluate life quality of subjects at each The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. | at 30 days, 6 and 12 months and 2, 3, 4, 5 years post-implantation compared to baseline | 
| Changes in frailty (KATZ questionnaire) | Assesses the ability of patients to conduct activities of daily living by questions in KATZ questionnaire. We use dependent(0 points) and independent(1 points) to evaluate bathing, dressing, toileting, transferring, contience and feeding activities of subjects. Total score is 6 points, the higher the score, the more indepent of subjects. | at 30 days, 12 months, 1, 2, 3, 4 and 5 years post-implantation compared to baseline | 
| Changes in cardiac function | defined as changes in cardiac function at each time point according to the NYHA Classification Scheme compared to baseline | at discharge, 30 days, 6 and 12 months and 2, 3, 4, 5 years post-implantation | 
| Rate of all-cause mortality | all-cause mortality including cardiovascular and non-cardiovascular | at 30 days, 6 months and 2, 3, 4, 5 years post-implantation | 
| Rate of main adverse cardiac and cerebral events (MACCE) | Rate of main adverse cardiac and cerebral events (MACCE) including disabling stroke, myocardial infarction, open surgery, and new permanent pacemaker at each time point | at 30 days, 6 and 12 months and 2, 3, 4, 5 years post-implantation | 
| Rate of life-threatening, disabling or severe bleeding (BARC 3 to 5) | BARC 3 to 5 defined as in BARC definition in annex of the protocol | at 30 days, 6 and 12 months and 2, 3, 4, 5 years post-implantation | 
| Rate of acute kidney injury network stage 2 and 3 or renal alternation therapy | renal alternation therapy including haemodialysis, peritoneal dialysis and hemofiltration | at 30 days, 6 and 12 months and 2 to 5 years | 
| Rate of implant related new and/or worsened conduction disturbances and arrhythmias, and occurrence of new permanent pacemaker implantation | Rate of implant related new and/or worsened conduction disturbances and arrhythmias, and occurrence of new permanent pacemaker implantation | at 30 days, 6 and 12 months and 2, 3, 4, 5 years post-implantation | 
| Rate of major vascular complications | vascular complications defined according to VARC2 definitions | at 30 days, 6 and 12 months and 2, 3, 4, 5 years post-implantation | 
| Rate of the occurrence of hospitalization | Rate of the occurrence of hospitalization for valve-related symptoms or worsening congestive heart failure | at 6, 12 months, and 2, 3, 4, 5 years post-implantation | 
| Rate of other TAVI-related adverse events | Rate of other TAVI-related adverse events (conversion to open surgery, unplanned used of cardiopulmonary bypass, coronary obstruction requiring intervention, ventricular septal perforation, mitral valve apparatus damage or dysfunction, cardiac tamponade, endocarditis, valve thrombosis, valve mal-positioning, TAV-in-TAV deployment, structural valve deterioration, valve related dysfunction or events requiring repeat procedure [BAV, TAVR, SAVR] | at 30 days, 6 and 12 months and at 2, 3, 4 and 5 years post implantation. |