Aortic Valve Stenosis
Conditions
Keywords
Aortic valve stenosis, TAVI, Balloon-expandable transcatheter heart valve, Self-expanding transcatheter heart valve,, heart valve disease
Brief summary
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
Interventions
DEVICEballoon-expandable valve
Sapien 3/Ultra, Edwards Lifesciences©
DEVICEself-expanding valve
Evolut R/Pro, Medtronic©
Sponsors
Ministry of Health, France
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
University Hospital, Lille
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| composite of: device technical failure at exit from procedure room and/or all-cause mortality and/or disabling stroke | at 90-day after TAVI | An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite of device failure, and/or all-cause mortality and/or disabling stroke | at 1 year after TAVI | An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions. |
| 2Composite of device technical failure, all-cause mortality and/or disabling stroke | At 90 days after TAVI | An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions. |
| Device technical failure | at exit from procedure room | 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 |
| Safety | at 90 days after TAVI | * 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 |
| Device Success | at 90 days after TAVI | * 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 |
| Clinical efficacy Clinical efficacy | at 1 year after TAVI | 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) |
| 11) Stage 2 or 3 hemodynamic valve deterioration | At 1 year after TAVI | according to VARC-3 n independent clinical event committee (CEC) adjudicate clinical events |
| device technical failure at exit from procedure room and/or all-cause mortality and/or disabling strok | at 3, 5, 7 and 10 years after TAVI | according to VARC-3 n independent clinical event committee (CEC) adjudicate clinical events |
| Valve-related clinical efficacy | at 1 year after TAVI | * 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 |
| composite outcome from a patient perspective | AT 90 days and 1 year afet TAVU | The rate of favourable outcome risk of death |
| Valve Durability defined as all-cause BVF tricuspid aortic valve | At 90days and 1 year after TAVI | An independant corelaboratory will review all images. An independent clinical event committee (CEC) will adjudicate clinical events according to the VARC-3 definitions. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 1) Rate of patients included in BEST Study successfully matched with the SNDS via the probabilistic linking algorithm of the FRANCE-TAVI registry. | at 1 year after TAVI | o A successful matching will be defined as \>98% of patients of the BEST study successfully matched with SNDS |
| 1) The rate of Hypoattenuated Leaflet Thrombosis (HALT) of any severity as assessed by CT-Scan and transthoracic echocardiography | at 1 year after TAVI | An independant corelaboratory will review all images |
Countries
France
Outcome results
None listed