Safety and Efficacy Comparison Of Two TAVI Systems in a Prospective Randomized Evaluation II (SCOPE II)

Safety and Efficacy Comparison Of Two TAVI Systems in a Prospective Randomized Evaluation II: A Randomized, Controlled, Non-inferiority Trial Evaluating Safety and Clinical Efficacy of the Symetis ACURATE Neo Compared to the Medtronic Evolut R Bioprosthesis in Transfemoral Transcatheter Aortic Valve Implantation

Current care randomized clinical trial comparing the CE marked Symetis ACURATE neo™ Aortic Bioprosthesis and ACURATE TF™ Transfemoral Delivery System with the CE marked Medtronic CoreValve Evolut R TAVI system (or any future CE-marked CoreValve versions).

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: Symetis ACURATE neo™ transfemoral TAVI system; Device: Medtronic CoreValve Evolut R TAVI System

Detailed Description

Transcatheter aortic valve implantation (TAVI) is an established and valuable treatment option for patients with severe symptomatic aortic stenosis and at high surgical risk for aortic valve replacement. The use of TAVI is rapidly expanding worldwide and its indications are widening into intermediate and lower risk populations. However, device comparisons by use of randomized trials are scarce in particular for newer generation transcatheter valves.

The Symetis ACURATE neo™, a self-expanding transcatheter valve delivered via transfemoral access, is a second-generation device that gained CE mark approval in June 2014.

The SCOPE-II trial will compare the safety and performance of the Symetis ACURATE neo™ with the self-expanding Medtronic Evolut R system, a widely used and well-established transcatheter heart valve, which obtained CE mark in 8NOV2006 and HAS approval on 13JAN2015.

• Study Type: Observational
• Enrollment (Actual): 796

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, DK-2100
    • Heart Center, Rigshospitalet, University of Copenhagen
• France
  • Brest, France, 29200
    • CHRU Brest Cavale Blanche
  • Lille, France, 59037
    • Centre Hospitalier Universitaire De Lille
  • Massy, France, 91300
    • Hopital Jacques Cartier
  • Toulouse, France, 31076
    • Clinique Pasteur
• Germany
  • Aachen, Germany, 52074
    • University Hospital Aachen
  • Bad Oeynhausen, Germany, 32545
    • Herz- und Diabeteszentrum NRW
  • Berlin, Germany, 13353
    • Deutsches Herzzentrum Berlin
  • Bernau bei Berlin, Germany, 16321
    • Herzzentrum Brandenburg, Immanuel Klinikum Bernau
  • Dortmund, Germany, 44137
    • St.-Johannes-Hospital
  • Dresden, Germany, 01307
    • Technische Universität Dresden
  • Essen, Germany, 45138
    • Elisabeth-Krankenhaus Essen
  • Frankfurt, Germany, 60323
    • Goethe-University Frankfurt
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig - Universitätsklinik
  • Munich, Germany, 80636
    • Deutsches Herzzentrum München des Freistaates Bayern
  • Munich, Germany, 80636
    • Klinik für Herz- & Kreislauferkrankungen - Deutsches Herzzentrum München
• Italy
  • Catania, Italy, 95124
    • University of Catania, Ferrarotto Hospital
  • Rozzano- (MI), Italy, 20089
    • Istituto Clinico Humanitas
  • San Donato, Italy, 20097
    • IRCCS Policlinico San Donato
  • San Raffaele, Italy, 20132
    • Ospedale San Raffaele
• Spain
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario Universitario de Santiago de Compostela
• United Kingdom
  • Leeds, United Kingdom
    • The Leeds Teaching Hospitals Nhs Trust
  • England
    • Brighton, England, United Kingdom, BN25BE
      • Brighton and Sussex University Hospital NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 71 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

764 patients presenting with severe symptomatic aortic stenosis with the indication for TAVI, as agreed by the Heart Team. If all eligibility criteria and none of the exclusion criteria are fulfilled, patients will be allocated in a 1:1 ratio to either the Symetis ACURATE neo™ or the Medtronic CoreValve Evolut R (or any future CE-marked CoreValve versions) by permuted block randomization.

Description

Inclusion Criteria:

• Patient with severe symptomatic aortic stenosis defined by a mean aortic gradient > 40 mmHg or peak jet velocity > 4.0 m/s or an aortic valve area (AVA) < 1cm2 or AVA indexed to body surface area (BSA) of <0.6 cm2/m2
• Patient is symptomatic (heart failure with New York Heart Association (NYHA) Functional Class > I, angina or syncope)
• Patients are considered at high risk for mortality with conventional surgical aortic valve replacement as assessed by a Heart Team consisting of a cardiologist and surgeon or as confirmed by a logistic EuroSCORE I > 20% and / or STS score > 10%.
• Aortic annulus diameter ranging from 21 to 26mm and perimeter rage from 66 - 81.7mm , based on ECG-gated multi-slice computed tomographic measurements. Findings of TTE, TEE and conventional aortography should be integrated in the anatomic assessment.
• Arterial aorto-iliac-femoral axis suitable for transfemoral access as assessed by conventional angiography and/or multi-detector computed tomographic angiography (access vessel diameter ≥ 6mm)
• 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
• Patient age 75 years or older
• Patient has given written consent to participate in the trial

Exclusion Criteria:

• Severely reduced left ventricular (LV) function (ejection fraction <20%)
• Pre-existing prosthetic heart valve in aortic and/or mitral position
• 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
• Severe coagulation conditions
• Inability to tolerate anticoagulation therapy
• Contraindication to contrast media or allergy to nitinol
• Active infection, including endocarditis
• Congenital aortic stenosis or unicuspid or bicuspid aortic valve
• Non-valvular aortic stenosis
• Hypertrophic obstructive cardiomyopathy
• New or untreated echocardiographic evidence of intracardiac mass, thrombus, or vegetation
• Non-calcific acquired aortic stenosis
• Severe eccentricity of calcification
• Anatomy not appropriate for transfemoral implant due to size, disease and degree of calcification or tortuosity of the aorta or ilio-femoral arteries
• Severe mitral regurgitation

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Symetis ACURATE neo™ transfemoral TAVI system; Patient assigned to this group will be implanted with Symetis ACURATE neo™ transfemoral TAVI system.	Device: Symetis ACURATE neo™ transfemoral TAVI system; Symetis ACURATE neo™ transfemoral TAVI system: Support frame made of nitinol, supra-annular processed tri-leaflet porcine pericardial valve and an outer skirt to mitigate paravalvular regurgitation (manufactured by Symetis SA, Ecublens, Switzerland).
Medtronic CoreValve Evolut R TAVI System; Patient assigned to this group will be implanted with Medtronic CoreValve Evolut R Transcatheter Aortic Valve Implantation (TAVI) System.	Device: Medtronic CoreValve Evolut R TAVI System; Medtronic CoreValve Evolut R Transcatheter Aortic Valve Implantation (TAVI) System (or any future CE-marked Corevalve versions): The support frame is manufactured from nitinol, which has multilevel, self-expanding properties and is radiopaque. The bioprosthesis is manufactured by suturing valve leaflets and a skirt from porcine pericardium into a tri-leaflet configuration (manufactured by Medtronic CoreValve LLC, Santa Ana, USA).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of all-cause mortality or stroke rates	The primary objective is to compare the composite of all-cause mortality or stroke rates at 1 year (powered for non-inferiority).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New permanent pacemaker rate	The first secondary objective is to compare the new permanent pacemaker rate at 30 days (powered for superiority).	30 days
All cause mortality at 30 days	All cause mortality	30 days
Stroke at 30 days	Stroke	30 days
Valve malpositioning at 30 days	Valve malpositioning	30 days
Peri-procedural myocardial infarction at 30 days	Peri-procedural myocardial infarction	30 days
Cardiac Tamponade at 30 days	Cardiac Tamponade	30 days
Implantation of multiple valves (TAV-in-TAV deployment) at 30 days	Implantation of multiple valves (TAV-in-TAV deployment)	30 days
Annular rupture/dissection at 30 days	- Annular rupture/dissection	30 days
Left ventricular perforation at 30 days	- Left ventricular perforation	30 days
Conversion to open heart surgery at 30 days	- Conversion to open heart surgery	30 days
Intra-procedural mortality (during index procedure)	- Intra-procedural mortality (during index procedure)	Procedurally
Procedural mortality (up to 72 hours after procedure)	- Procedural mortality (up to 72 hours after procedure)	Procedurally and up to 72 hours post-procedurally
Mortality (cardiac/non-cardiac) at 30 days and 1 year	- Mortality (cardiac/non-cardiac)	30 days and 1 year
All stroke (disabling/non disabling) at 30 days and 1 year	- All stroke (disabling/non disabling)	30 days and 1 year
Composite of all-cause mortality or disabling stroke at 30 days and 1 year	- Composite of all-cause mortality or disabling stroke	30 days and 1 year
Hospitalization for valve-related symptoms or worsened congestive heart at 30 days and 1 year	- Hospitalization for valve-related symptoms or worsened congestive heart failure	30 days and 1 year
Life-threatening/major bleeding at 30 days and 1 year	- Life-threatening/major bleeding (BARC 3b or more)	30 days and 1 year
Myocardial infarction at 30 days and 1 year	- Myocardial infarction	30 days and 1 year
Valve related dysfunction requiring repeat procedure at 30 days and 1 year	- Valve related dysfunction requiring repeat procedure (BAV, TAVI or SAVR)	30 days and 1 year
Endocarditis at 30 days and 1 year	- Endocarditis	30 days and 1 year
Valve thrombosis at 30 days and 1 year	- Valve thrombosis	30 days and 1 year
New AV-conduction disturbances at 30 days and 1 year	- New AV-conduction disturbances (LBBB only)	30 days and 1 year
New pacemaker implantation at 1 year	- New pacemaker implantation at 1 year	1 year
Any arrhythmia resulting in hemodynamic instability or requiring therapy at 30 days and 1 year	Any arrhythmia resulting in hemodynamic instability or requiring therapy	30 days and 1 year
VARC-2 combined endpoints at 30 days	Composite of device success, early safety, clinical efficacy and time-related valve safety	30 days
Time-related valve safety at 1 year	Time-related valve safety	1 year
Echocardiographic endpoint (1)	- Structural valve deterioration	Post-procedurally [day 1 to 7], at 30 days, 1 year
Echocardiographic endpoint (2)	- Prosthetic aortic valve stenosis	Post-procedurally [day 1 to 7], at 30 days, 1 year
Echocardiographic endpoint (3)	- Patient prosthesis mismatch	Post-procedurally [day 1 to 7], at 30 days, 1 year
Echocardiographic endpoint (4)	- Aortic regurgitation (grading), proportion of more than mild regurgitation	Post-procedurally [day 1 to 7], at 30 days, 1 year
Echocardiographic endpoint (5)	- Intended valve performance: No prosthesis mismatch, mean aortic valve gradient <20 mmHg or peak velocity <3 m/s, without moderate or severe prosthetic valve aortic regurgitation.	Post-procedurally [day 1 to 7], at 30 days, 1 year
Echocardiographic endpoint (6)	- Systolic LV ejection fraction	Post-procedurally [day 1 to 7], at 30 days, 1 year
Echocardiographic endpoint (7)	- LV diastolic function	Post-procedurally [day 1 to 7], at 30 days, 1 year
Echocardiographic endpoint (8)	- Left atrial volume	Post-procedurally [day 1 to 7], at 30 days, 1 year
Echocardiographic endpoint (9)	- Right ventricular (RV) dimension and function	Post-procedurally [day 1 to 7], at 30 days, 1 year
Echocardiographic endpoint (10)	- Right atrial (RA) area	Post-procedurally [day 1 to 7], at 30 days, 1 year
Echocardiographic endpoint (11)	- RV/RA-ratio and estimated systolic pulmonary arterial pressure	Post-procedurally [day 1 to 7], at 30 days, 1 year

Collaborators and Investigators

• Sponsor: Ceric Sàrl
• Collaborators: Symetis SA
• Investigators: Principal Investigator: Corrado Tamburino, Prof, MD, PhD, Cardiology Division and Cardio-Thoracic & Vascular Department, Ferrarotto & Policlinico Hospitals, University of Catania, Italy; Principal Investigator: Sabine Bleiziffer, MD, Herz- und Diabeteszentrum NRW, Bad Oeynhausen, Germany

Publications and helpful links

General Publications

• Tamburino C, Bleiziffer S, Thiele H, Scholtz S, Hildick-Smith D, Cunnington M, Wolf A, Barbanti M, Tchetche D, Garot P, Pagnotta P, Gilard M, Bedogni F, Van Belle E, Vasa-Nicotera M, Chieffo A, Deutsch O, Kempfert J, Sondergaard L, Butter C, Trillo-Nouche R, Lotfi S, Mollmann H, Joner M, Abdel-Wahab M, Bogaerts K, Hengstenberg C, Capodanno D. Comparison of Self-Expanding Bioprostheses for Transcatheter Aortic Valve Replacement in Patients With Symptomatic Severe Aortic Stenosis: SCOPE 2 Randomized Clinical Trial. Circulation. 2020 Dec 22;142(25):2431-2442. doi: 10.1161/CIRCULATIONAHA.120.051547. Epub 2020 Oct 15.

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2017
• Primary Completion (Actual): June 4, 2020
• Study Completion (Actual): June 4, 2020

Study Registration Dates

• First Submitted: March 30, 2017
• First Submitted That Met QC Criteria: June 16, 2017
• First Posted (Actual): June 20, 2017

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 10, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: SCOPE II

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