Safety and Efficacy of SinocrownTM Transcatheter Aortic Valve Replacement System

Study Overview
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Brief Summary
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This study was designed to preliminary verify the safety and of efficacy of SinocrownTM Transcatheter Aortic Valve Replacement System With accessories in patients with symptomatic, calcified and severe aortic stenosis using objective performance criteria

Detailed Description
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This prospective, single-center, single-arm clinical trial was designed to preliminary confirm the safety and efficacy of SinocrownTM transcatheter aortic valve system with accessories. According to the inclusion and exclusion criteria, 10 patients were enrolled and implanted with SinocrownTM .Patients will been followed up 30 days, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after valve implantation. The main follow-up included clinical symptoms and signs, cardiac ultrasound, etc. The primary endpoint was device success after TAVR, Secondary endpoints included procedural success, all-cause mortality, myocardial infarction, disabling stroke, severe bleeding, acute kidney injury, permanent pacemaker implantation, vascular complications, other complication, MACCEs, valvular function , cardiac function improvement, quality of life of patients.

Official Title
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A Prospective，Multicenter, Single-arm Clinical Trial to Evaluate Safety and Efficacy of SinocrownTM Transcatheter Aortic Valve Replacement System With Accessories in Patients With Symptomatic, Calcified and Severe Aortic Stenosis

Conditions
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Transcatheter Aortic Valve Replacement

Intervention / Treatment
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* Device: SinocrownTM Transcatheter Aortic Valve Replacement System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 65 years ; Autologous degenerative aortic stenosis（evaluated by echocardiography: transaortic valve pressure gradient ≥40mmHg , or transaortic valve blood flow rate ≥4m/s, or aortic Valve area<1.0cm2, or AVA <0.5cm2 /m2） Patients with aortic annulus size≥17.5mm and ≤29mm (echocardiography measurement); The diameter of the ascending aorta of the patient was < 45mm. Appear obvious symptoms caused by aortic stenosis, NYHA class Ⅱ to IV; Subject or subject's legal representative have been informed of the nature of the study, agrees to participate and has signed the approved consent form. Subjects are willing to accept all clinical follow-up. The cardiologist and cardiac surgeon evaluated the subject as unsuitable for surgical treatment (the risk of death or irreversible complications within 30 days after operation is expected to be above 50% , or contraindicated comorbidities such as prior chest radiotherapy, liver failure, diffuse severe calcification of the aorta, extreme weakness, etc.). Or Moderate or higher surgical risk (STS score ≥ 4%). Exclusion Criteria: defined as Q-wave myocardial infarction or non-Q-wave myocardial infarction with CK-MB level ≥ 2 times the upper limit of normal value and / or Tn increase. Subjects with congenital unicuspid, without calcification. Any therapeutic or traumatic cardiac surgery within 30 days (within 3 months in case of drug-eluting stents implantation) The patient's heart has been implanted with other artificial heart valves, artificial rings, or severe mitral annulus calcification (MAC), severe (> 3 +) mitral insufficiency. Hematological abnormalities, including leukopenia (WBC<3×109/L), acute anemia (HB <90g/L), thrombocytopenia (PLT<50×109/L), bleeding constitution and coagulopathy ； Subjects with hemodynamic instability, requiring continuous mechanical heart assistance. Subjects who need emergency surgery for any reason; Hypertrophic cardiomyopathy with or without obstruction; Severe left ventricular dysfunction, left ventricular ejection fraction (LVEF) <20%; The echocardiogram indicates the presence of a thrombus or vegetation; A history of active peptic ulcer or upper gastrointestinal bleeding within 3 months; Are allergic to nickel titanium alloys or contrast agents, and cannot tolerate anticoagulation and antiplatelet therapy; Cerebrovascular accident occurred within 6 months, including transient ischemic attack; renal insufficiency(creatinine> 3.0mg/dL) and/or end-stage renal disease requiring Renal dialysis; Life expectancy< 12 months; Significant aortic diseases, including abdominal aortic or thoracic aortic aneurysm(defined as maximum lumen diameter > 50mm, obvious distortion), atherosclerosis of the aortic arch(especially bulge with thickness > 5mm or ulceration), narrowing of the abdominal or thoracic aorta(especially calcification and irregular surface), and severe curvature of the thoracic aorta; The iliac-femoral artery cannot be inserted with a guide sheath of 22F or above, such as severely obstructed with calcification, severely tortuous or vessel diameter less than 6mm; Screening participant who is participating in other drug or medical device clinical trials; Active infective endocarditis or other active infections; Anatomically, the approach or aortic root is not suitable for TAVR (such as a high risk of coronary artery occlusion). Other conditions considered by the investigator to be inappropriate for participation in this clinical trial.

Ages Eligible for Study
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Minimum Age: 65 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: SinocrownTM Transcatheter Aortic Valve Replacement System<br>The experimental apparatus consisted of artificial aortic valve, transporter and grip-loading system. | Device: SinocrownTM Transcatheter Aortic Valve Replacement System<br>* Subjects receiving SinocrownTM Transcatheter Aortic Valve Replacement System of Lepu Medical<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| device success | Immediate postoperative device success was defined as : successfully loading the valve into the delivery system, sending it to the target site through the delivery system, accurately releasing the artificial aortic valve and completely withdrawing the delivery system (valve orifice area > 1.2cm2, mean aortic gradient< 20mmhg or maximal aortic valve velocity < 3 m/ s, and there is no moderate or severe valve stenosis) | immediate post-surgical | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedural success | Device success without death and aortic valve reintervention during operation | immediate post-surgical | 
| All-cause mortality | including cardiac, non-cardiac and unexplained deaths | immediate post-surgical, 7 days after procedure/prior to discharge, 30 days, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years | 
| Myocardial infarction | Rate of patients with myocardial infarction | immediate post-surgical, 7 days after procedure/prior to discharge, 30 days, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years | 
| Rate of disabling stroke | Disabling stroke was defined as mRS ≥ 2, and the mRS score increased by more than 1 point compared with the last visit | 7 days after procedure/prior to discharge, 30 days, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years | 
| Rate of Severe bleeding(life-threatening or disabling) | Severe degree was defined as type 3a or above（according to BARC） | 7 days after procedure/prior to discharge, 30 days, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years | 
| acute kidney injury | Rate of patients with acute kidney injury | 7 days after procedure/prior to discharge, 30 days after procedure | 
| permanent pacemaker implantation | Rate of patients implanted with permanent pacemaker | 7 days after procedure/prior to discharge, 30 days, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years | 
| vascular complications | Vascular complications mainly include dissection, occlusion, rupture and bleeding of access vessels. | immediate post-surgical, 7 days after procedure/prior to discharge | 
| other operative complication | including conversion to surgery, unexpected cardiopulmonary mechanical assistance, coronary artery occlusion, ventricular septal perforation, mitral valve injury or loss of function, pericardial tamponade, endocarditis, valve thrombosis, valve ectopic (displacement, embolization, misrelease), and so on. | immediate post-surgical, 7 days after procedure/prior to discharge | 
| The incidence of major adverse cardiovascular and cerebrovascular events during the trial(MACCEs) | Incidence of MACCEs (including mortality, stroke, myocardial infarction, reoperation, arrhythmias and conduction blocks) during the trial. | immediate post-surgical, 7 days after procedure/prior to discharge, 30 days, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years | 
| Valve and heart function | Doppler echocardiography was used to evaluate the valve performance at each follow-up point, including valve orifice area, mean aortic gradient, degree of valve regurgitation, left ventricular ejection fraction LVEF, end diastolic left ventricular inner diameter LVEDd, moderate or above perivalvular leakage PVL, and degree of aortic stenosis. | immediate post-surgical, 7 days after procedure/prior to discharge, 30 days, 6 months, 12 months | 
| Cardiac function improvement | Cardiac function improvement is accessed by NYHA cardiac function classification increases from baseline to discharge, 30 days, 6 months, 12 months | 7 days after procedure/prior to discharge, 30 days, 6 months, 12 months | 
| Quality of life of patients | Quality of Life of patients accessed by EuroQol-5 Dimensions (EQ-5D) Questionnaire. The higher scores mean a better health state. Recording changes from baseline to 30 days, 6 months, 12 months | 30 days, 6 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aortic stenosis