TAVR vs. SAVR Study of VitaFlow Liberty® for Severe BAV Stenosis

Not Applicable

Not yet recruiting

• Conditions: Aortic Stenosis; Bicuspid Aortic Valve (BAV)
• Interventions: Device: VitaFlow Liberty; Device: Commercially available surgical bioprosthetic valve

• Registration Number: NCT06597188
• Lead Sponsor: Shanghai MicroPort CardioFlow Medtech Co., Ltd.

Brief Summary

To evaluate the safety and effectiveness of the Transcatheter aortic valve and retrievable delivery system (VitaFlow Liberty®) for the treatment of severe bicuspid aortic valve (BAV) stenosis.

Detailed Description

Transcatheter aortic valve replacement (TAVR) has emerged as the first-line treatment for symptomatic severe AS currently, while TAVR for bicuspid aortic valve (BAV) stenosis has not been well demonstrated in randomized controlled trials, thus more randomized controlled studies of TAVR vs. SAVR are still needed to provide strong evidence that TAVR treatment for patients with BAV stenosis has good safety and effectiveness.

This study is a prospective, international multicenter, randomized controlled, non-inferiority clinical study, in which the study device (VitaFlow Liberty®) for TAVR is to be demonstrated as non-inferior to the control device (a commercially available surgical bioprosthetic valve) for SAVR in terms of the incidence of composite endpoint events (all-cause mortality, all strokes and re-hospitalizations) at 12 months postoperatively.

In this study, 452 eligible subjects will be randomly assigned to the study group (n=226) or the control group (n=226) in a 1:1 ratio. The subjects in study group will be treated with the TAVR surgery using the study device (VitaFlow Liberty®) , while the subjects in control group will be treated with the SAVR surgery using the control device (a commercially available surgical bioprosthetic valve), and clinical follow-ups will be performed at discharge (or 7 days after surgery), 30 days, 6 months, 12 months, and 2, 3, 4, 5 years after surgery, respectively.

Study Timeline

• Study First Submitted: 2024-09-10
• Study First Submitted QC: 2024-09-13
• Study First Posted: 2024-09-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-10
• Study Start: 2025-04-21
• Primary Completion: 2028-09-30
• Study Completion: 2032-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 452

Inclusion Criteria

1. Subject aged ≤ 75 years;
2. With symptomatic severe bicuspid aortic stenosis, defined as: peak flow velocity ≥ 4.0m/s, or mean trans-aortic pressure gradient ≥ 40mmHg, or aortic orifice area (AVA) ≤ 1.0cm2 (or AVA index ≤ 0.6cm2/m2) confirmed by echocardiography；
3. New York Heart Association (NYHA) cardiac function classification ≥ Class II;
4. With an intermediate or low risk of surgical procedures (STS score ≤8%) assessed by the local heart team;
5. Voluntarily participate in this study and sign the informed consent form.

Exclusion Criteria

1. Known allergy or resistance to study device and control device components such as nitinol or contrast media;
2. Known contraindication or allergy to anticoagulant or antiplatelet medications and inability to tolerate the anticoagulant or antiplatelet therapy;
3. Known presence of active infective endocarditis or other active infection;
4. Known presence of severe vascular disease that precludes safe implantation of the prosthetic valve;
5. Ascending aorta width ≥50mm;
6. Previous prosthetic valve implantation (mechanical or bioprosthetic) in any heart place;
7. The aortic root anatomy not suitable for transcatheter aortic valve implantation confirmed by preoperative imaging (including aortic root calcification that influence the sufficient dilatation of the rposthetic valve);
8. Intracardiac mass, left ventricular or left atrial thrombus, vegetations confirmed by preoperative echocardiography;
9. Acute myocardial infarction (defined as Q-wave MI or non-Q-wave MI) within 30 days prior to surgery;
10. Invasive therapeutic cardiac surgery within 30 days prior to surgery (except for temporary pacemaker or implantable cardioverter-defibrillator implantation);
11. Clinically diagnosed stroke or TIA within 3 months prior to surgery;
12. Gastrointestinal bleeding requiring hospitalization or transfusion therapy or other clinically significant bleeding or coagulation disorders within 3 months prior to surgery, which preclude the required antiplatelet therapy in the study;
13. Comorbid with severe native coronary artery lesions that require revascularization therapy;
14. Comorbid with severe mitral or tricuspid regurgitation;
15. Comorbid with cardiogenic shock or hemodynamic instability requiring support from positive inotropic agents or mechanical ventilation or mechanical cardiac assistance;
16. Comorbid with severe left ventricular dysfunction (defined as left ventricular ejection fraction LVEF <20%);
17. Comorbid with end-stage renal diseases requiring chronic dialysis;
18. Comorbid with blood dyscrasias defined as leukopenia (white blood cell count < 3×109/L), thrombocytopenia (platelet count < 50×109/L), history of bleeding diathesis or coagulopathy, or hypercoagulable states;
19. Subjects corresponding to the criteria of a vulnerable population (including patients who are unable to fully understand all aspects of the study, patients lacking capacity in the informed consent procedure and patients with dementia and cognitive impairment);
20. Female subjects known to be pregnant or lactating;
21. Life expectancy is less than 12 months as assessed by the investigator;
22. Subject is participating in or planning to participate in other drug or device clinical studies within 12 months postoperatively;
23. Any other condition that, at the discretion of investigator or heart team, may preclude the subject's safe participation in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TAVR group	VitaFlow Liberty	TAVR with the study device will be performed in the TAVR group
SAVR group	Commercially available surgical bioprosthetic valve	SAVR with a commercially available surgical bioprosthetic valve will be performed in the control group

Primary Outcome Measures

Name	Time	Method
Incidence of composite endpoint events (all-cause mortality, all strokes, and re-hospitalizations [surgery, valve or heart failure related re-hospitalizations])	12 months postoperatively	The composite endpoint event at 12 months postoperatively refers to all-cause mortality, all strokes, and re-hospitalizations related to procedure, valve or heart failure that occur within 12 months postoperatively.

Secondary Outcome Measures

Name	Time	Method
New York Heart Association grading assessment of cardiac function	Discharge, 30 days, 6 months, 12 months, 2-5 years postoperatively	New York Heart Association (NYHA) grading system includes four gradings with higher grading means severer outcome.
Quality of life assessment (Kansas City Cardiomyopathy Questionnaire score)	30 days, 6 months, 12 months postoperatively	Kansas City Cardiomyopathy Questionnaire (KCCQ) score is ranged from 0 to 100 with higher score means better quality of life.
Incidence of all strokes	30 days, 6 months, 12 months, 2 to 5 years postoperatively	According to the VARC3 criteria, all strokes include ischemic strokes (including TIAs), hemorrhagic strokes, and unspecified strokes, as well as disabling and non-disabling strokes.
Incidence of myocardial infarction	Discharge, 30 days, 6 months, 12 months, 2-5 years postoperatively	Myocardial infarction in this study is defined according to the VARC3 criteria.
Incidence of life-threatening or disabling major bleeding	30 days, 6 months, 12 months, 2-5 years postoperatively	Life-threatening or disabling major bleeding is defined as types 3 and 4 bleeding according to the VARC3 criteria.
Incidence of acute kidney injury (AKI)	Discharge, 30 days postoperatively	According to the VARC3 criteria, AKI is defined as stages 2-4 acute kidney injury.
Incidence of conduction disturbance and arrhythmias	30 days, 6 months, 12 months, 2-5 years postoperatively	Conduction disturbance and arrhythmias are defined according to the VARC3 criteria.
Incidence of permanent pacemaker implantation	30 days, 6 months, 12 months, 2-5 years postoperatively	Defined as the percentage of subjects with newly permanent pacemaker implantation occurring after surgery among all subjects enrolled in each group.
Incidence of serious vascular complications	30 days, 6 months, 12 months postoperatively	Serious vascular complications are defined according to the VARC3 criteria.
Incidence of Bioprosthetic valve dysfunction (BVD)	12 months, 2-5 years postoperatively	BVD includes structural valve deterioration (SVD), moderate and severe prosthesis-patient mismatch (PPM), moderate and severe paravalvular leak (PVL), thrombosis or endocarditis.
Bioprosthetic valve dysfunction (BVF)	12 months, 2-5 years postoperatively	BVF is a composite endpoint, including severe HVD, aortic valve reintervention, and valve-related mortality (investigator assessment).
Re-hospitalization related to procedure, valve or heart failure	30 days, 6 months, 12 months, 2-5 years postoperatively	Re-hospitalization related to procedure, valve or heart failure is defined according to the VARC3 criteria.
Incidence of adverse events (AEs)	throughout the clinical study period	An AE is an untoward medical occurrence during the course of the clinical study, regardless of whether or not related to the study device
Device success rate	30 days postoperatively	Device success is defined as meeting all the following criteria: 1. Correct positioning of a single prosthetic heart valve into the proper anatomical location; 2. Successful access, delivery of the device, and retrieval of the delivery system; 3. Freedom from mortality; 4. Freedom from surgery or intervention related to the devicea or to a major vascular or access-related or cardiac structural complication; 5. Intended performance of the valvec (mean gradient \<20mmHg, peak velocity \<3 m/s, Doppler velocity index ≥ 0.25, and less than moderate aortic regurgitation).
Prosthetic valve performance evaluation	30 days, 6 months, 12 months, 2-5 years postoperatively	The prosthetic valve performance will be evaluated independently by the corelab based on the echocardiography.
All-cause mortality	30 days, 6 months, 12 months, 2-5 years postoperatively	According to the VARC3 criteria, all-cause mortality includes cardiovascular mortality and non-cardiovascular mortality.
Incidence of major adverse cardiovascular and cerebrovascular events (MACCE)	30 days, 6 months, 12 months postoperatively	MACCE includes all-cause mortality, myocardial infarction, all strokes, and reoperation due to valvular dysfunction, with each event defined according to the VARC3 criteria.
Incidence of other TAVR-related complications	Immediately, 30 days, 6 months, 12 months, 2-5 years postoperatively	Other TAVR-related complications include: conversion to surgery, unplanned cardiopulmonary mechanical assistance, coronary artery occlusion requiring intervention, ventricular septal perforation, mitral valve damage or dysfunction, cardiac tamponade, endocarditis, valvular thrombosis, valvular dyslocation (displacement, embolization, false release), and reoperation due to valve dysfunction (including surgical or interventional therapy).
Moderate to severe structural valvular deterioration (HVD)	12 months, 2-5 years postoperatively	Moderate HVD is defined as an increase in mean transvalvular gradient ≥ 10mmHg resulting in mean gradient ≥ 20mmHgc with concomitant decrease in EOA ≥ 0.3cm2 or ≥ 25% and/or decrease in Doppler velocity index ≥ 0.1 or ≥ 20% compared with echocardiographic assessment performed 1-3 months post-procedure, OR new occurrence or increase of ≥ 1 graded of intraprosthetic AR resulting in ≥ moderate AR.; Severe HVD is defined as an increase in mean transvalvular gradient ≥ 20mmHg resulting in mean gradient ≥ 30mmHgc with concomitant decrease in EOA ≥ 0.6cm2 or ≥50% and/or decrease in Doppler velocity index ≥0.2 or ≥40% compared with echocardiographic assessment performed 1-3 months post-procedure, OR new occurrence, or increase of ≥ 2 grades,d of intraprosthetic AR resulting in severe AR
Incidence of serious adverse events (SAEs)	throughout the clinical study period	Serious adverse event (SAE) refers to any adverse event that occurs during the clinical study of a medical device that results in any of the following: 1. Leads to death, or; 2. Leads to serious deterioration of the health conditions, including: Fatal disease or injury Permanent defect in the physical structure or physical function Requiring hospitalization or prolongation of hospital stay Any event which requires medical or surgical intervention to prevent persistent disability/incapacity; 3. Leads to fetal distress, fetal death or congenital abnormality or congenital defect, etc.; Note: Planned hospitalizations due to pre-existing disease conditions, or events that do not result in significant deterioration in health status due to procedures required by the clinical study program are not considered SAEs.