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Safety and Efficacy of the Symetis ACURATE Neo/TF Compared to the Edwards SAPIEN 3 Bioprosthesis. (SCOPE I)

I

Insel Gruppe AG, University Hospital Bern

Status

Completed

Conditions

Aortic Valve Stenosis

Treatments

Device: Edwards Sapien 3 Transcatheter Heart Valve
Device: Symetis ACURATE neo/TF transfemoral TAVI system

Study type

Interventional

Funder types

Other

Identifiers

NCT03011346
V 4.0, 13.08.2018

Details and patient eligibility

About

Transcatheter aortic valve implantation (TAVI) is an established treatment option for patients with severe symptomatic aortic stenosis and at increased risk for surgical aortic valve replacement (SAVR). Many novel devices are currently being developed and established transcatheter heart valves undergo design reiterations to address limitations and reduce complication rates associated with the device and implantation procedure. However, device comparisons by use of randomized trials are scarce in particular for newer generation transcatheter valves. The aim of this study is to assess non-inferiority of the self-expandable Symetis ACURATE neo/TF in comparison to the balloon-expandable Edwards SAPIEN 3 transcatheter aortic valve bioprosthesis with regard to early safety and clinical efficacy at 30 days.

Full description

Background:

Transcatheter aortic valve implantation (TAVI) is an established and valuable treatment option for patients with severe symptomatic aortic stenosis and at increased risk for surgical aortic valve replacement (SAVR). The use of TAVI is rapidly expanding worldwide and the indications for TAVI are widening into lower risk populations in view of favorable outcomes among high and intermediate risk patients. Many novel devices are currently developed or established devices undergo design reiterations to address limitations, such as vascular access complications, paravalvular regurgitation, and atrio-ventricular conductance disturbances. However, device comparisons by use of randomized trials are scarce in particular for newer generation transcatheter valves.

The Symetis ACURATE neo/TF, a self-expandable transcatheter valve delivered via transfemoral access, gained Conformité Européenne (CE) marking in September 2014 after showing favorable procedural and short term results. The SCOPE I trial will compare its performance to the balloon-expandable Edwards SAPIEN 3, a widely used and well-established transcatheter heart valve of the second generation, in a randomized fashion.

Objectives:

The primary objective is the comparison of the Symetis ACURATE neo/TF to the Edwards SAPIEN 3 transcatheter aortic bioprosthesis with regard to early safety and clinical efficacy at 30 days. Secondary objectives involve the comparison between the two devices with regard to secondary clinical and echocardiographic endpoints at 30 days, 1 year and 3 years.

Methods:

Sample Size: Based on an anticipated incidence proportion of 22% for the primary non-hierarchical composite endpoint at 30 days in both treatment arms, a non-inferiority margin of 7.7%, a power of 80%, a one-tailed significance level of α = 0.05, and a low attrition rate, the total required sample size amounts to 730 patients.

Design: Patients will be allocated to the Symetis ACURATE neo/TF or the Edwards SAPIEN 3 bioprosthesis at a 1:1 ratio by means of a randomly permuted block randomisation stratified on study center and Society of Thoracic Surgeons' predicted risk of mortality score (STS-PROM) strata (< 3%, ≥ 3 to < 8%, ≥ 8%).

Analysis: Estimates of the risk-differences between the two treatment arms with regard to the primary endpoint will be pooled over the predefined STS-PROM strata by means of the Cochran-Mantel-Haenszel method and Wald-type confidence limits will be calculated using the Sato variance estimator. The non-inferiority assumption will be tested at a one-sided significance level with a type I error rate (α) = 0.05. The analysis of the primary composite endpoint will be conducted according to the intention-to-treat (ITT) and the per protocol (PP) principle and non-inferiority should be claimed only if met by both.

In case non-inferiority is established, a superiority analysis will be performed using a two-tailed significance level with a type I error rate of α = 0.05. Further secondary analyses will evaluate between group differences in relation to demographic, clinical, procedural, functional and imaging characteristics. Pre-specified subgroup analyses will be conducted by use of appropriate interaction tests contrasting categories of sex, STS-PROM score (< 3%, ≥ 3 to < 8%, ≥ 8%), left ventricular ejection fraction (< 50% vs. ≥ 50%), and native aortic valve eccentricity index (≤ 0.25 vs. > 0.25).

Enrollment

739 patients

Sex

All

Ages

75+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Patient with severe aortic stenosis defined by an aortic valve area (AVA) < 1cm2 or AVA indexed to body surface area (BSA) of < 0.6 cm2/m2, including low-flow severe aortic stenosis defined by stroke volume index (SVI) < 35ml/m2, as assessed by integration of echocardiographic and invasive measurements

  • Subject is symptomatic (heart failure symptoms with New York Heart Association (NYHA) Functional Class > I, angina or syncope)

  • Patient is considered at increased risk for mortality if undergoing conventional surgical aortic valve replacement or judged as not operable as determined either

    • by a Logistic EuroSCORE > 20 % OR
    • by a STS-PROM score > 10% OR
    • by the heart team consisting of at least one cardiologist and cardiac surgeon based on the integration of individual clinical and anatomical factors not captured by risk-scores, the patient's age, frailty and life-expectancy
  • The heart team agrees on eligibility of the patient for participation and that TAVI by transfemoral access constitutes the most appropriate treatment modality, from which the patient will likely benefit most

  • Aortic annulus dimensions suitable for both valve types (area range: 338-573 mm2 AND perimeter range: 66-85 mm) based on ECG-gated multislice computed tomographic measurements. Findings of transesophageal echocardiography (TEE) and conventional aortography should be integrated in the anatomic assessment if available

  • Arterial aorto-iliac-femoral axis suitable for transfemoral access with a minimum access vessel diameter ≥ 6 mm as assessed by multislice computed tomographic angiography and/or conventional angiography

  • Written informed consent of the patient or her/his legal representative

  • Patient understands the purpose, the potential risks as well as benefits of the trial and is willing to participate in all parts of the follow-up

Exclusion criteria

  • Non-valvular aortic stenosis
  • Congenital aortic stenosis or unicuspid or bicuspid aortic valve
  • Non-calcific acquired aortic stenosis
  • Anatomy not appropriate for transfemoral transcatheter aortic valve implantation due to size of the aortic annulus or degree or eccentricity of calcification of the native aortic valve or tortuosity of the aorta or ilio-femoral arteries
  • Emergency procedure including patients in cardiogenic shock (low cardiac output, vasopressor dependence, mechanical hemodynamic support)
  • Severely reduced left ventricular (LV) function (ejection fraction < 20%)
  • Pre-existing prosthetic heart valve in aortic position
  • Presence of mitral valve prosthesis
  • Concomitant planned procedure except for percutaneous coronary intervention (PCI)
  • Planned non-cardiac surgery within 30 days
  • Stroke within 30 days of the procedure.
  • Myocardial infarction within 30 days of the procedure (except type 2)
  • Evidence of intra-cardiac mass, thrombus or vegetation
  • Severe coagulation conditions
  • Inability to tolerate anticoagulation/anti-platelet therapy
  • Active bacterial endocarditis or other active infections
  • Hypertrophic cardiomyopathy with or without obstruction
  • Contraindication to contrast media or allergy to nitinol
  • Participation in another trial, which would lead to deviations in the preparation or performance of the intervention or the post-implantation management from this protocol

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

739 participants in 2 patient groups

Symetis ACURATE neo/TF transfemoral TAVI system
Active Comparator group
Description:
Symetis ACURATE neo/TF transfemoral TAVI system: self-expandable transcatheter aortic bioprosthesis, support frame made of nitinol, supra-annular processed trileaflet porcine pericardial valve and an outer skirt to mitigate paravalvular regurgitation (manufactured by Symetis SA, Ecublens, Switzerland)
Treatment:
Device: Symetis ACURATE neo/TF transfemoral TAVI system
Edwards Sapien 3 Transcatheter Heart Valve
Active Comparator group
Description:
Edwards SAPIEN 3 Transcatheter Heart Valve system: balloon-expandable transcatheter aortic bioprosthesis, support frame made of cobalt-chromium, three leaflets constructed of processed bovine pericardial tissue and an outer polyethylene terephthalate (PET) sealing cuff to mitigate paravalvular regurgitation (manufactured by Edwards Lifesciences, Inc., Irvine, California, USA)
Treatment:
Device: Edwards Sapien 3 Transcatheter Heart Valve

Trial contacts and locations

20

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Data sourced from clinicaltrials.gov

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