Balloon-Expandable Versus Self-expanding Transcatheter Heart Valve for Treatment of Symptomatic Native Aortic Valve Stenosis (BEST) (BEST)

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

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 and /or disabling stroke 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

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: balloon-expandable valve; Device: self-expanding valve

• Study Type: Interventional
• Enrollment (Actual): 1960
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Annecy, France
    • Ch Annecy Genevois
  • Besançon, France
    • CHU de Besançon
  • Caen, France
    • CHU de CAEN
  • Caen, France
    • Hôpital privé Saint-Martin
  • Clermont-Ferrand, France
    • CHU de Clermont-Ferrand
  • Créteil, France
    • AP-HP Hôpitaux Universitaires Henri Mondor
  • Grenoble, France
    • CHU de Grenoble
  • Massy, France
    • Institut Cardiovasculaire Paris Sud
  • Montpellier, France
    • CHU de Montpellier
  • Nîmes, France
    • CHU de Nîmes
  • Paris, France
    • Institut Mutualiste Montsouris
  • Paris, France
    • AP-HP Hôpitaux Universitaires Pitié Salpêtrière
  • Pessac, France
    • CHU de Bordeaux Hôpital Pellegrin
  • Reims, France
    • CHU Reims - Hôpitam Robert Debré
  • Saint-Etienne, France
    • CHU de Saint-Etienne
  • Saint-Herblain, France
    • CHU de Nantes - Hopital Laennec
  • Saint-Laurent-du-Var, France
    • Centre Médico Chirurgical Arnault Tzanck
  • Strasbourg, France
    • CHU de Strasbourg
  • Toulouse, France
    • CHU de Toulouse
  • Tours, France
    • CHU de Tours
  • Villeurbanne, France
    • Médipole Lyon Villeurbanne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite of: device technical failure at exit from procedure room and/or all-cause mortality and/or disabling stroke	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
Composite of device failure, and/or all-cause mortality and/or disabling stroke	An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions.	at 1 year after TAVI
2Composite of device technical failure, all-cause mortality and/or disabling stroke	An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions.	At 90 days after TAVI
Device technical failure	Freedom from mortality, Successful access, delivery of the device and retrieval of the delivery system, Correct positioning of a single prosthetic heart valve into the proper anatomical location, Freedom from surgery or intervention related to the device or to a major vascular or access-related, or cardiac structural complication	at exit from procedure room
Safety	Technical success at exit from procedure room (VARC 3)*; Freedom from all-cause mortality; Freedom from all stroke; Freedom from VARC type 2-4 bleeding; Freedom from major vascular access-related complication; Freedom from cardiac structural complication; Freedom from acute kidney injury stage 3 or 4; Freedom from moderate or severe aortic regurgitation; Freedom from new permanent pacemaker due to procedure-related conduction abnormalities; Freedom from surgery or intervention related to the device	at 90 days after TAVI
Device Success	Technical success at exit from procedure room; Freedom from mortality; Freedom form surgery or intervention related to the device or to a major vascular or access-related or major cardiac structural complication; Intended performance of the valve (mean gradient < 20mmHg, peak velocity <3m/s, Doppler Velocity index ≥ 0.25, and less than moderate aortic regurgitation	at 90 days after TAVI
Clinical efficacy Clinical efficacy	Ao Technical success at exit from procedure room (VARC 3)*; Freedom from all-cause mortality; Freedom from all stroke; Freedom from hospitalization for procedure- or valve-related causes; Freedom from KCCQ Overall Summary Score <45 or decline from baseline of >10 point (i.e. Unfavourable Outcome)	at 1 year after TAVI
Valve-related clinical efficacy	Technical success of the TAVI procedure*; Intended performance of the valve; Freedom from severe PPM at discharge (or 90 days)†; Freedom from endocarditis†; Freedom from bioprosthesis Valve Failure (BVF); Freedom from stroke or peripheral embolism (presumably valve-related, after ruling out other non-valve aetiologies); Freedom from VARC Type 2-4 bleeding secondary to or exacerbated by antiplatelet or anticoagulant agents, used specifically for valve-related concerns	at 1 year after TAVI
composite outcome from a patient perspective	The rate of favourable outcome risk of death	AT 90 days and 1 year afet TAVU
Valve Durability defined as all-cause BVF tricuspid aortic valve	An independant corelaboratory will review all images. An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions.	At 90days and 1 year after TAVI
11) Stage 2 or 3 hemodynamic valve deterioration	according to VARC-3 n independent clinical event committee (CEC) adjudicate clinical events	At 1 year after TAVI
device technical failure at exit from procedure room and/or all-cause mortality and/or disabling strok	according to VARC-3 n independent clinical event committee (CEC) adjudicate clinical events	at 3, 5, 7 and 10 years after TAVI

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
1) Rate of patients included in BEST Study successfully matched with the SNDS via the probabilistic linking algorithm of the FRANCE-TAVI registry.	o A successful matching will be defined as >98% of patients of the BEST study successfully matched with SNDS	at 1 year after TAVI
1) The rate of Hypoattenuated Leaflet Thrombosis (HALT) of any severity as assessed by CT-Scan and transthoracic echocardiography	An independant corelaboratory will review all images	at 1 year after TAVI

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Ministry of Health, France; Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
• Investigators: Principal Investigator: Eric Van Belle, MD,PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2023
• Primary Completion (Actual): October 29, 2025
• Study Completion (Estimated): December 29, 2035

Study Registration Dates

• First Submitted: July 7, 2022
• First Submitted That Met QC Criteria: July 7, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Aortic valve stenosis; TAVI; heart valve disease; Balloon-expandable transcatheter heart valve; Self-expanding transcatheter heart valve,
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Heart Valve Diseases
• Other Study ID Numbers: 2021_0513; 2021-A02554-37 (Other Identifier: ID-RCB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No