Overview
This is a prospective, multicenter, randomized controlled clinical study designed to evaluate the real-world performance of the VitaFlow Liberty® Flex Transcatheter Aortic Valve Retrievable and Steerable Delivery System (Investigational Device) for treating severe aortic stenosis (AS) in challenging anatomies. The study will compare it against the VitaFlow Liberty® Retrievable Delivery System (Control Device), which lacks steerability.
Key Study Elements:
Objective: The primary objective is to assess the device's performance using the incidence of a composite endpoint before hospital discharge. This endpoint includes permanent pacemaker implantation (PPI), valve-in-valve (ViV) implantation, or moderate-to-severe paravalvular leakage (PVL).
Design: A prospective, multicenter RCT with 1:1 randomization (Experimental: VitaFlow Liberty® Flex vs. Control: VitaFlow Liberty®). Approximately 15 sites in China will participate. Subjects undergo follow-up at discharge, 30 days, and 1 year post-procedure. An independent data center handles management and analysis.
Population: Patients with severe AS (echo confirmed: peak velocity ≥4.0 m/s, mean gradient ≥40 mmHg, or AVA ≤1.0 cm²/AVAi ≤0.6 cm²/m²) AND preoperative CTA showing a challenging aortic-left ventricular angle >60°. NYHA class ≥II is required.
- Devices
Investigational: VitaFlow Liberty® Flex (Retrievable & Steerable Delivery System - Models DSRS21/24/27/30/A series; Loading Tools LT-S series).
Control: VitaFlow Liberty® (Retrievable Delivery System - Models DSR21/24/27/30; Loading Tools LT series).
- Endpoints
Primary: Composite of PPI, ViV, or moderate-to-severe PVL before discharge.
Secondary: Include individual components of the primary endpoint (ViV, PVL) immediately post-procedure, procedural success (VARC-3), technical assistance rates, valve retrievals, implantation depth, arch/valve crossing performance, valve hemodynamics (gradient, area, leak, LVEF), NYHA class, Major Adverse Cardiac and Cerebrovascular Events (MACCE - all-cause death, MI, stroke, reoperation), major vascular complications (at discharge/30 days).
Key Inclusion: Severe AS, challenging anatomy (aortic-LV angle >60°), NYHA ≥II, informed consent.
Key Exclusions: Device/contrast allergies, anticoagulant intolerance, active infection, severe vascular disease prohibiting access, ascending aorta ≥55mm, unsuitable aortic root anatomy, intracardiac mass/thrombus, recent MI (<30 days), severe concomitant mitral/tricuspid regurgitation, cardiogenic shock, severe LV dysfunction (LVEF<20%), hematologic abnormalities, pregnancy/breastfeeding, participation in other device trials.
Visits: Screening (≤30d pre-op), Procedure (intra-op to 24h post-op), Discharge (≤7d post-op), 30d Follow-up (±7d), 12m Telephone FU (±1m).
Sample Size: Planned enrollment of 232 subjects (116 per group), calculated for superiority testing. Based on an expected composite endpoint rate of 21% for the Flex system vs. a historical rate of 38% for non-steerable systems (Superiority margin Δ1=0%, one-sided α=2.5%, Power=80%, accounting for 5% dropout).
Purpose: This study aims to demonstrate the superiority of the retrievable and steerable VitaFlow Liberty® Flex delivery system in reducing the composite rate of key adverse events (PPI, ViV, significant PVL) at discharge compared to the non-steerable system, specifically in patients with severe AS and anatomically challenging aortic-left ventricular angles.
Description
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
3. Investigational and Control Devices
Device Component：VitaFlow Liberty® FLEX (Investigational) VitaFlow Liberty® (Control) Delivery System Type：Retrievable & Steerable(Investigational) Retrievable (Non-Steerable)(Control)
4. 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
5. 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.
6. 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
7. 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.
8. 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.
9. 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.
Eligibility
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.