- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03011346
Safety and Efficacy of the Symetis ACURATE Neo/TF Compared to the Edwards SAPIEN 3 Bioprosthesis. (SCOPE I)
Safety and Efficacy of the Symetis ACURATE Neo/TF Compared to the Edwards SAPIEN 3 Bioprosthesis for Transcatheter Aortic Valve Implantation by Transfemoral Approach.
Study Overview
Status
Conditions
Detailed 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).
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Augsburg, Germany, 86156
- Klinkum Augsburg
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Bad Berka, Germany, 99437
- Zentralklinik Bad Berka
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Bad Bevensen, Germany, 29549
- Herz- und Gefässzentrum Bad Beversen
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Bad Nauheim, Germany, 61231
- Kerckhoff-klinik
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Dortmund, Germany, 44137
- St.-Johannes-Hospital
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Dresden, Germany, 01307
- Herzzentrum Dresden
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Hamburg, Germany, 20251
- Universitäres Herzzentrum Hamburg GmbH
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Karlsruhe, Germany, 76133
- Städtisches Klinikum Karlsruhe
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Karlsruhe, Germany, 76135
- ViDia Kliniken
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Karlsruhe, Germany, 76185
- Klinik für Herzchirurgie Karlsruhe
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Köln, Germany, 50931
- Herzzentrum Uniklinik Köln
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Leipzig, Germany, 04289
- Herzzentrum Leipzig
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München, Germany, 80636
- Deutsches Herzzentrum München
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Regensburg, Germany, 93053
- Klinik und Poliklinik für Herz-, Thorax- und herznahe Gefäßchirurgie
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Bad Neustadt
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Bad Neustadt An Der Saale, Bad Neustadt, Germany, 97616
- Herz- und Gefäß-Klinik GmbH Bad Neustadt
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Utrecht, Netherlands, 3584 CX
- University Medical Center Utrecht
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Bern, Switzerland, 3010
- Bern University Hospital
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Luzern, Switzerland, 6000
- Luzerner Kantonsspital
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Zürich, Switzerland, 8091
- Universitatsspital Zurich
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London, United Kingdom, SE1 7EH
- St Thomas' Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Symetis ACURATE neo/TF transfemoral TAVI system
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)
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Transcatheter aortic valve implantation of a Symetis ACURATE neo/TF bioprosthesis by transfemoral access, pre-dilatation mandatory.
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Active Comparator: Edwards Sapien 3 Transcatheter Heart Valve
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)
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Transcatheter aortic valve implantation of an Edwards Sapien 3 bioprosthesis by transfemoral access.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Modified* combined early safety and clinical efficacy as defined by the Valve Academic Research Consortium-2 (VARC-2)
Time Frame: 30 days
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(* "NYHA class III or IV" is omitted due to lack of objectiveness in its ascertainment)
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30 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Device success
Time Frame: 30 days
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Combined endpoint composed of:
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30 days
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Early safety
Time Frame: 30 days
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Combined endpoint composed of:
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30 days
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Clinical efficacy
Time Frame: 30 days
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Combined endpoint composed of:
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30 days
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Time-related valve safety
Time Frame: 30 days, 1 year
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Combined endpoint composed of:
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30 days, 1 year
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All-cause mortality
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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All stroke (disabling and non-disabling)
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Life-threatening or disabling bleeding
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Acute kidney injury (stage 2 or 3, including renal replacement therapy)
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Coronary artery obstruction requiring intervention
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Major vascular complication
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Valve related dysfunction requiring repeat procedure (balloon aortic valvuloplasty, TAVI or SAVR in a separate intervention)
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Rehospitalization for valve-related symptoms or worsening congestive heart failure
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Valve-related dysfunction: prosthetic aortic valve stenosis AND/OR ≥ moderate prosthetic valve regurgitation
Time Frame: 30 days, 1 year, 3 years
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Prosthetic aortic valve stenosis: mean gradient ≥ 20 mmHg, EOA ≤ 0.9-1.1cm2
and/or DVI < 0.35)
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30 days, 1 year, 3 years
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Conversion to open heart surgery
Time Frame: procedural
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procedural
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Annular rupture
Time Frame: procedural
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procedural
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New pacemaker implantation
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Valve thrombosis
Time Frame: 30 days, 1 year, 3 years
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Any thrombus attached to or near an implanted valve that occludes part of the blood flow path, interferes with valve function, or is sufficiently large to warrant treatment.
Note that valve-associated thrombus identified at autopsy in a patient whose cause of death was not valve-related should not be reported as valve thrombosis.
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30 days, 1 year, 3 years
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Mean trans-prosthetic aortic gradient
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Aortic regurgitation
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score
Time Frame: 30 days, 1 year, 3 years
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30 days, 1 year, 3 years
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Collaborators and Investigators
Investigators
- Principal Investigator: Thomas Pigrim, Prof. MD, Bern University Hospital, Dep. of Cardiology, 3010 Bern, Switzerland
Publications and helpful links
General Publications
- Lanz J, Kim WK, Walther T, Burgdorf C, Mollmann H, Linke A, Redwood S, Thilo C, Hilker M, Joner M, Thiele H, Conzelmann L, Conradi L, Kerber S, Schymik G, Prendergast B, Husser O, Stortecky S, Heg D, Juni P, Windecker S, Pilgrim T; SCOPE I investigators. Safety and efficacy of a self-expanding versus a balloon-expandable bioprosthesis for transcatheter aortic valve replacement in patients with symptomatic severe aortic stenosis: a randomised non-inferiority trial. Lancet. 2019 Nov 2;394(10209):1619-1628. doi: 10.1016/S0140-6736(19)32220-2. Epub 2019 Sep 27.
- Kim WK, Walther T, Burgdorf C, Mollmann H, Linke A, Redwood S, Thilo C, Hilker M, Joner M, Thiele H, Conzelmann L, Conradi L, Kerber S, Schymik G, Prendergast B, Husser O, Blumenstein J, Stortecky S, Heg D, Kunzi A, Juni P, Windecker S, Pilgrim T, Lanz J; SCOPE I Investigators. One-Year Outcomes of a Randomized Trial Comparing a Self-Expanding With a Balloon-Expandable Transcatheter Aortic Valve. Circulation. 2021 Mar 23;143(12):1267-1269. doi: 10.1161/CIRCULATIONAHA.120.052251. Epub 2021 Mar 22. No abstract available.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- V 4.0, 13.08.2018
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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