Prospective, Multicenter, Randomized Controlled Clinical Study Evaluating the VitaFlow Liberty® Flex Transcatheter Aortic Valve Delivery System for the Treatment of Severe Aortic Stenosis Lesions

A Prospective, Multicenter, Randomized Controlled Clinical Trial Evaluating the VitaFlow Liberty® Flex Transcatheter Aortic Valve Retrievable and Steerable Delivery System for Severe Aortic Stenosis in Challenging Anatomies

• Study Rationale and Objective Severe aortic stenosis (AS) carries significant morbidity and mortality when untreated. Transcatheter aortic valve replacement (TAVR) has emerged as a standard therapy, yet complex aortic anatomies - particularly steep aortic-left ventricular (LV) angles - present technical challenges during valve delivery, potentially leading to suboptimal deployment, paravalvular leak (PVL), conduction disturbances requiring permanent pacemaker implantation (PPI), or valve-in-valve (ViV) placement. The VitaFlow Liberty® Flex Delivery System addresses this with its retrievable and steerable catheter technology designed for enhanced navigability. This prospective, multicenter, randomized controlled trial (RCT) aims to evaluate the real-world superiority of the investigational VitaFlow Liberty® Flex System versus the non-steerable VitaFlow Liberty® System in patients with severe AS and challenging anatomies (aortic-LV angle >60°). The primary objective is to compare the incidence of a composite safety endpoint (PPI, ViV implantation, or moderate-to-severe PVL) before hospital discharge.
• Study Design

Type: Prospective, multicenter, open-label, 1:1 randomized controlled superiority trial

Randomization: Centralized electronic system

Blinding: Unblinded (procedural nature precludes blinding)

Study Arms:

Experimental: VitaFlow Liberty® Flex TAVR System (Retrievable & Steerable)

Control: VitaFlow Liberty® TAVR System (Retrievable, Non-Steerable)

Follow-up Schedule:

Pre-discharge (≤7 days post-op)

30 days (±7 days)

12 months (±1 month, telephone)

Oversight: Independent Clinical Events Committee (CEC), Data Monitoring Committee (DMC), and Core Laboratories for imaging/ECG analysis

Centers: ~15 experienced TAVR centers across China

• Investigational and Control Devices

Device Component：VitaFlow Liberty® FLEX (Investigational) VitaFlow Liberty® (Control) Delivery System Type：Retrievable & Steerable(Investigational) Retrievable (Non-Steerable)(Control)

• Study Population

Diagnosis: Severe symptomatic AS confirmed by echocardiography:

Peak aortic velocity ≥4.0 m/s OR Mean gradient ≥40 mmHg OR Aortic valve area (AVA) ≤1.0 cm² (or AVAi ≤0.6 cm²/m²) Anatomical Inclusion: Pre-op CT angiography (CTA) with 3D reconstruction demonstrating aortic-LV angle >60° (validating challenging anatomy).

Symptoms: NYHA Functional Class ≥II.

Key Exclusion Criteria:

Allergy to device materials (nitinol), contrast, or antiplatelets/anticoagulants Active infection/endocarditis Severe vascular disease prohibiting access Ascending aorta diameter ≥55mm Unsuitable aortic root anatomy (e.g., heavy calcification affecting expansion) Intracardiac thrombus/mass Recent MI (<30 days) Severe mitral/tricuspid regurgitation LVEF <20% Hematologic disorders (leukopenia, thrombocytopenia, coagulopathy) Pregnancy or concurrent device trials

• Endpoints

Primary Endpoint:

Composite of PPI, ViV implantation, or moderate-to-severe PVL before discharge.

Secondary Endpoints:

Procedural:

ViV rate (immediate post-op) Moderate-to-severe PVL (immediate post-op) Technical assistance crossing rate Valve retrieval attempts Valve implantation depth Arch/valve crossing performance Procedural success (VARC-3 criteria*)

Clinical:

PPI rate (discharge, 30 days) MACCE** (discharge, 30 days): All-cause death, MI, stroke, reoperation Major vascular complications

Hemodynamic/Echocardiographic:

Valve orifice area, mean gradient, peak velocity Degree of stenosis/regurgitation LVEF (immediate, discharge, 30 days)

Functional: NYHA Class improvement (discharge, 30 days)

*VARC-3: Valve Academic Research Consortium-3 criteria for technical success.

**MACCE: Major Adverse Cardiac and Cerebrovascular Events.

• Statistical Analysis & Sample Size Hypothesis: Superiority of VitaFlow Liberty® Flex

Assumptions:

Historical composite endpoint rate (non-steerable systems): 38% Expected composite rate (steerable system): 21% Superiority margin (Δ1): 0% Power: 80% | One-sided α: 2.5% | Dropout: 5% Sample Size: 232 subjects (116 per arm)

Analysis:

Primary endpoint: Chi-square/Fisher's exact test Secondary endpoints: Mixed-effects models accounting for site variability Subgroup analyses: Valve size, center volume, baseline aortic-LV angle

• Study Procedures

Screening (≤30 days pre-op): Echocardiography, CTA, NYHA assessment, informed consent.

Procedure: TAVR under standard anesthesia. Randomization pre-insertion. Discharge (≤7 days): Echo, ECG, NYHA, MACCE/vascular complication assessment. 30-Day Visit: Clinical exam, echo, ECG, lab tests, NYHA, MACCE. 12-Month Follow-up: Telephone assessment for mortality/MACCE.

• Ethical & Regulatory Considerations

Approved by institutional review boards (IRBs) at all sites. Conducted per ICH-GCP, Declaration of Helsinki, and Chinese regulatory requirements.

Independent DMC reviews safety data quarterly.

• Significance and Innovation

This trial addresses a critical unmet need in TAVR: improving outcomes in patients with challenging aortic anatomies. If superiority is demonstrated, the steerable delivery system may become the preferred option for:

Reducing PPI rates (linked to anatomical precision) Mitigating PVL (via optimal deployment) Avoiding ViV (through recapture/repositioning) Enhancing first-attempt success in tortuous anatomies

Conclusion:

This rigorously designed RCT will provide Level A evidence on the clinical utility of steerable TAVR technology in high-risk anatomies, potentially establishing a new standard for managing complex AS patients.

Inclusion criteria

• Diagnosis of severe aortic stenosis, defined as: echocardiographically confirmed peak aortic valve velocity ≥4.0 m/s, or mean aortic valve gradient ≥40 mmHg, or aortic valve area (AVA) ≤1.0 cm2 (or AVA index ≤0.6 cm2/m2);
• Preoperative cardiac and great vessel CT angiography (CTA) with 3D reconstruction demonstrating an aortic-left ventricular angle >60°, indicating potential challenges for arch crossing and valve crossing;
• New York Heart Association (NYHA) functional class ≥II;
• Voluntary participation in the study with signed informed consent.

Exclusion criteria

• Known allergy or intolerance to components of the investigational or control devices (e.g., nitinol) or contrast agents;
• Contraindication or known allergy to anticoagulant or antiplatelet therapy, rendering the patient unable to tolerate such treatment;
• Known active infective endocarditis or other active infections;
• Known severe vascular disease that would preclude safe prosthetic valve implantation;
• Ascending aorta width ≥55mm;
• Pre-procedural imaging shows aortic root anatomy unsuitable for transcatheter aortic valve implantation (including aortic root calcification that may affect proper valve expansion);
• Pre-procedural echocardiography shows intracardiac mass, left ventricular or left atrial thrombus, or vegetation;
• Acute myocardial infarction within 30 days prior to procedure (defined as Q-wave MI or non-Q-wave MI);
• Concomitant severe mitral or tricuspid regurgitation;
• Concomitant cardiogenic shock or hemodynamic instability requiring inotropic support, mechanical ventilation, or mechanical cardiac assistance;
• Concomitant severe left ventricular dysfunction (defined as left ventricular ejection fraction LVEF<20%);
• Concomitant hematologic abnormalities defined as leukopenia (WBC count <3×109/L), thrombocytopenia (platelet count <30×109/L), history of bleeding diathesis or coagulopathy, or hypercoagulable state;
• Female subjects known to be pregnant or breastfeeding;
• Subjects currently participating in or planning to participate in other drug or device clinical studies within 12 months postoperatively; Any other condition that the investigator or heart team deems may hinder the subject's safe participation in the study.