Title:

The ULTRA-EVOLUT Randomized Control Trial: A Head-to-Head Comparison of Latest-Generation Transcatheter Aortic Valves

Brief Summary:

The goal of this clinical trial is to compare the latest-generation balloon-expandable (SAPIEN 3 Ultra Resilia) versus self-expanding (Evolut FX) transcatheter aortic valves in patients with severe, symptomatic aortic stenosis who are undergoing transcatheter aortic valve implantation (TAVI).

The main questions it aims to answer are:

Does device success rate (defined by VARC-3 criteria) at 30 days differ between the SAPIEN 3 Ultra Resilia and the Evolut FX valves? Do hemodynamic performance (mean gradient, effective orifice area) and incidence of moderate/severe paravalvular leak differ between the two valve types at 30 days and 1 year? Researchers will compare patients randomized to receive the SAPIEN 3 Ultra Resilia valve versus patients randomized to receive the Evolut FX valve to see if there are differences in device success, safety outcomes, and valve performance.

Participants will:

Undergo standard pre-procedural clinical, echocardiographic, and CT assessment Be randomly assigned to receive either the SAPIEN 3 Ultra Resilia or Evolut FX valve during their clinically indicated TAVI procedure Receive post-procedure follow-up assessments including echocardiography and clinical evaluation at 24 hours, 30 days, 6 months, and 1 year

Study Design Overview

This is a prospective, randomized, controlled, single-blind, two-arm parallel-group trial conducted at a single tertiary cardiac care center. The study aims to compare the latest-generation balloon-expandable transcatheter heart valve (SAPIEN 3 Ultra Resilia) versus the latest-generation self-expanding transcatheter heart valve (Evolut FX) in patients with severe symptomatic aortic stenosis who are deemed appropriate for transcatheter aortic valve implantation (TAVI) by the local heart team.

Scientific Rationale

Previous landmark trials (e.g., PARTNER 3 and Evolut Low Risk) have established the safety and efficacy of TAVI in intermediate- to low-risk patients. However, direct head-to-head comparisons between the newest commercially available valve iterations-the SAPIEN 3 Ultra Resilia (featuring anti-calcification tissue treatment) and the Evolut FX (offering enhanced radial strength and conformability)-are lacking. Observational and registry data suggest potential differences in paravalvular leak rates, hemodynamic performance, and permanent pacemaker implantation rates, but randomized evidence is needed to eliminate bias and guide evidence-based, patient-specific valve selection.

Study Population and Enrollment

Consecutive patients with severe aortic stenosis (aortic valve area ≤1.0 cm², mean gradient ≥40 mmHg, or peak velocity ≥4.0 m/s), symptomatic (NYHA functional class II-IV), and anatomically suitable for both valve types will be screened for eligibility. Key exclusion criteria include bicuspid aortic valve, severe mitral or tricuspid regurgitation, prior aortic valve replacement, active endocarditis, and contraindication to anticoagulation.

A total of approximately 200 patients will be randomized in a 1:1 ratio to receive either the SAPIEN 3 Ultra Resilia or the Evolut FX valve. Sample size calculation assumes a 90% device success rate in both arms, 80% power, and a two-sided alpha of 0.05.

Randomization and Blinding

Randomization will be performed using a computer-generated sequence with variable block sizes. Allocation concealment will be maintained using sequentially numbered, opaque, sealed envelopes. The study is single-blind: outcome assessors and echocardiography core laboratory analysts will be blinded to valve type assignment. Operators and procedural staff cannot be blinded due to the inherent differences in valve delivery systems and deployment techniques.

Procedural and Follow-Up Protocol

All TAVI procedures will be performed according to international standards and local clinical practice. Post-procedure, patients will undergo clinical assessment, 12-lead electrocardiography, and transthoracic echocardiography at 24 hours, 30 days, 6 months, and 1 year. Adverse events will be adjudicated according to Valve Academic Research Consortium-3 (VARC-3) criteria.

Data Management and Statistical Analysis

Data will be collected prospectively using standardized case report forms and entered into a password-protected electronic database. Analysis will be performed using SPSS version 26.0 or later. Continuous variables will be compared using independent t-test or Mann-Whitney U test, and categorical variables using chi-square or Fisher's exact test. Time-to-event outcomes will be analyzed using Kaplan-Meier curves and log-rank tests. A two-sided p-value <0.05 will be considered statistically significant.

Ethical and Regulatory Considerations

The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Ethical approval has been obtained from the institutional review board. Written informed consent will be obtained from all participants prior to any study-related procedures. The trial will be registered on ClinicalTrials.gov prior to enrollment of the first participant. Results will be submitted for publication in a peer-reviewed journal regardless of the outcome.

Inclusion Criteria:

• Severe aortic stenosis defined as aortic valve area (AVA) ≤1.0 cm², mean transvalvular gradient ≥40 mmHg, or peak transvalvular velocity ≥4.0 m/s
• Symptomatic with New York Heart Association (NYHA) functional class II, III, or IV
• Heart team consensus that transcatheter aortic valve implantation (TAVI) is the appropriate treatment strategy
• Anatomically suitable for both valve types (SAPIEN 3 Ultra Resilia and Evolut FX) as determined by pre-procedural computed tomography (CT) imaging
• Age ≥18 years
• Able and willing to provide written informed consent
• Able and willing to comply with all scheduled follow-up visits and assessments

Exclusion Criteria:

• Bicuspid aortic valve morphology
• Severe mitral regurgitation or severe tricuspid regurgitation requiring intervention
• Prior surgical or transcatheter aortic valve replacement
• Active infective endocarditis
• Contraindication to dual antiplatelet therapy or anticoagulation
• Estimated life expectancy less than 1 year due to non-cardiac comorbidities
• Pregnancy or breastfeeding