Balloon-expandable vs Self-Expanding Transcatheter Heart Valve

Study Overview
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Brief Summary
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Over the last years, several randomized studies comparing transcatheter aortic valve implantation (TAVI) to surgical aortic valve replacement (SAVR) have established TAVI as a treatment option in symptomatic patients with aortic stenosis (AS) (1,2,3). Most transcatheter heart valves (THV) available are designed on either a balloon-expandable (BE) or a self-expanding (SE) concept. Despite major differences, both designs are recommended to be used indifferently in most of the clinical situations and a significant number of centers only implant one of this two THV design. It remains unclear however, whether these 2 very different THV concepts are achieving similar or different clinical outcomes and could be considered a single Class of device. While there is an urgent clinical need to clarify this issue in an exponentially growing therapeutic field, to date no large randomized study powered to compare the 2 THV designs on individual endpoints has been conducted or initiated. Recently, two large-scale French registry-based propensity matched analyses, including more than 30,000 patients, have reported a higher 90 days and 1-year mortality with the use of SE as compared to BE-valve (4,5). However, as the propensity-score matching-approach cannot rule out residual confounders, and as some of the most recent THV iterations were not part of the investigation, there is an urgent need to conduct a randomized trial sufficiently powered to compare head-to-head the latest generation of SE and BE-valve on all-cause mortality. In addition, two small randomized studies have recently showed the inferiority of a new SE-valve compared to BE-valve and SE-THV (SCOPE1 trial, J Lanz. Lancet. 2019 Nov 2;394(10209):1619-1628. and SCOPE 2 trial, Circulation in press), thus further questioning wether THV should be considered as a single Class regardless the THV design. The objective of the present randomized clinical investigation will be to evaluate the impact of THV design (SE vs BE) on the risk of all-cause mortality at 90 days and 1 year. The present clinical investigation will the first randomized clinical investigation to compare head to head the benefit of BE-valve over SE-valve on total mortality at 90 days and 1-year using a superiority design. Previous head-to-head studies included only a small number of patients, non-inferiority designs and combined endpoints. This clinical investigation will be the first to generate sufficient evidences to change clinical practice and international guidelines to clarify whether one THV design is superior (or not) to the other one (BE vs SE-valve). The result of the clinical investigation is key for clinicians indicating the treatment and for the patients receiving the treatment

Official Title
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Balloon-Expandable Versus Self-expanding Transcatheter Heart Valve for Treatment of Native Aortic Valve Stenosis

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: balloon-expandable valve
* Device: self-expanding valve


Participation Criteria
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Eligibility Criteria
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The study population will be comprised of all patients with severe, calcific, symptomatic aortic stenosis eligible to percutaneous transfemoral TAVI with BE or SE-valve according to the investigating center heart team. The inclusion/exclusion criteria are limited and primarily intend to select patient eligible to both BE and SE-valve. This allows for a study cohort whose composition is expected to be close to an all-comers cohort and therefore representative for the standard TAVI population seen in daily practice. Inclusion Criteria: Symptomatic severe aortic stenosis defined according to the current echocardiography criteria of the European Society of Cardiology guidelines2. Heart team of the investigating center agrees that the patient is eligible to TAVI with BE-valve SAPIEN 3 (Edwards Lifesciences©) (or further iterations of the same family) OR TAVI with the SE-valve Evolut-R/pro (Medtronic©) (or futher iterations of the same family). Heart team of the investigating center agrees that TAVI is feasible via percutaneous transfemoral approach. Written informed consent to the BEST study Written informed consent to the FRANCE-TAVI registy All valve anatomy are authorized (bicuspid or tricuspid aortic valve) Exclusion Criteria: Age < 18 years old Patient with legal protection Non-affiliation to a social security scheme Pregnancy Subject participating in another research protocol on TAVI procedure Patients presenting with an anatomy that is regarded unsuitable for the implantation of one of the two valve types TAVI through nontransfemoral approach or surgical cutdown Valve-in-valve procedure (TAVI in TAVI or TAVI in surgical aortic bioprosthesis) Implantation of Accurate Neo or Accurate Neo2 valve (Boston scientific) Severe aortic regurgitation (>3+) Refusal to participate to FRANCE-TAVI registry

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAVI with balloon-expandable valve (Sapien 3/Ultra, Edwards Lifesciences©)<br> | Device: balloon-expandable valve<br>* Sapien 3/Ultra, Edwards Lifesciences©<br>|
| Active Comparator: TAVI with self-expanding valve (Evolut R/Pro, Medtronic©)<br> | Device: self-expanding valve<br>* Evolut R/Pro, Medtronic©<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions. | at 90-day after TAVI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Technical success | An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions. | At exit from procedure room | 
| Rate of Device Success | An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions. | At 90 days | 
| Rate of Early safety | An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions. | At 90 days | 
| All-cause mortality at 1 year | An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions. | At 1 year after procedure | 
| All-stroke or TIA at 1 year |  | At 1 year after procedure | 
| All hospitalization for heart failure | An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions. | After post implant period, at 90 days, at 1 year after procedure | 
| All hospitalization for procedure- or valve-related causes |  | After post implant period, at 90 days, at 1 year after procedure | 
| Baseline clinical and echocardiographic parameters | An independant corelaboratory will review all images and | At Basline, after post implant period, at 90 days, at 1 year after procedure | 
| Baseline anatomical aortic valve CT-scan parameters including Valve morphology: bicuspid vs. tricuspid aortic valve | An independant corelaboratory will review all images | At Basline, after post implant period, at 90 days, at 1 year after procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic valve stenosis, TAVI, Balloon-expandable transcatheter heart valve, Self-expanding transcatheter heart valve,, heart valve disease