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

Aortic Valve Stenosis Clinical Trial

— SCOPE II  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03192813
• Other study ID #: SCOPE II
• Status: Completed
• Start date: April 20, 2017
• Est. completion date: June 4, 2020

Study information

• Verified date: June 2020
• Source: Ceric Sàrl
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 796
• Est. completion date: June 4, 2020
• Est. primary completion date: June 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Valve Stenosis

Intervention

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
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).

Locations

Country	Name	City	State
Denmark	Heart Center, Rigshospitalet, University of Copenhagen	Copenhagen
France	CHRU Brest Cavale Blanche	Brest
France	Centre Hospitalier Universitaire de Lille	Lille
France	Hôpital Jacques Cartier	Massy
France	Clinique Pasteur	Toulouse
Germany	University Hospital Aachen	Aachen
Germany	Herz- und Diabeteszentrum NRW	Bad Oeynhausen
Germany	Deutsches Herzzentrum Berlin	Berlin
Germany	Herzzentrum Brandenburg, Immanuel Klinikum Bernau	Bernau bei Berlin
Germany	St.-Johannes-Hospital	Dortmund
Germany	Technische Universität Dresden	Dresden
Germany	Elisabeth-Krankenhaus Essen	Essen
Germany	Goethe-University Frankfurt	Frankfurt
Germany	Herzzentrum Leipzig - Universitätsklinik	Leipzig
Germany	Deutsches Herzzentrum München des Freistaates Bayern	Munich
Germany	Klinik für Herz- & Kreislauferkrankungen - Deutsches Herzzentrum München	Munich
Italy	University of Catania, Ferrarotto Hospital	Catania
Italy	Istituto Clinico Humanitas	Rozzano- (MI)
Italy	IRCCS Policlinico San Donato	San Donato
Italy	Ospedale San Raffaele	San Raffaele
Spain	Complejo Hospitalario Universitario de Santiago de Compostela	Santiago de Compostela
United Kingdom	Brighton and sussex University hospital NHS trust	Brighton	England
United Kingdom	The Leeds Teaching Hospitals NHS TRUST	Leeds

Sponsors (2)

Lead Sponsor	Collaborator
Ceric Sàrl	Symetis SA

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	New permanent pacemaker rate	The first secondary objective is to compare the new permanent pacemaker rate at 30 days (powered for superiority).	30 days
Secondary	All cause mortality at 30 days	All cause mortality	30 days
Secondary	Stroke at 30 days	Stroke	30 days
Secondary	Valve malpositioning at 30 days	Valve malpositioning	30 days
Secondary	Peri-procedural myocardial infarction at 30 days	Peri-procedural myocardial infarction	30 days
Secondary	Cardiac Tamponade at 30 days	Cardiac Tamponade	30 days
Secondary	Implantation of multiple valves (TAV-in-TAV deployment) at 30 days	Implantation of multiple valves (TAV-in-TAV deployment)	30 days
Secondary	Annular rupture/dissection at 30 days	- Annular rupture/dissection	30 days
Secondary	Left ventricular perforation at 30 days	- Left ventricular perforation	30 days
Secondary	Conversion to open heart surgery at 30 days	- Conversion to open heart surgery	30 days
Secondary	Intra-procedural mortality (during index procedure)	- Intra-procedural mortality (during index procedure)	Procedurally
Secondary	Procedural mortality (up to 72 hours after procedure)	- Procedural mortality (up to 72 hours after procedure)	Procedurally and up to 72 hours post-procedurally
Secondary	Mortality (cardiac/non-cardiac) at 30 days and 1 year	- Mortality (cardiac/non-cardiac)	30 days and 1 year
Secondary	All stroke (disabling/non disabling) at 30 days and 1 year	- All stroke (disabling/non disabling)	30 days and 1 year
Secondary	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
Secondary	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
Secondary	Life-threatening/major bleeding at 30 days and 1 year	- Life-threatening/major bleeding (BARC 3b or more)	30 days and 1 year
Secondary	Myocardial infarction at 30 days and 1 year	- Myocardial infarction	30 days and 1 year
Secondary	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
Secondary	Endocarditis at 30 days and 1 year	- Endocarditis	30 days and 1 year
Secondary	Valve thrombosis at 30 days and 1 year	- Valve thrombosis	30 days and 1 year
Secondary	New AV-conduction disturbances at 30 days and 1 year	- New AV-conduction disturbances (LBBB only)	30 days and 1 year
Secondary	New pacemaker implantation at 1 year	- New pacemaker implantation at 1 year	1 year
Secondary	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
Secondary	VARC-2 combined endpoints at 30 days	Composite of device success, early safety, clinical efficacy and time-related valve safety	30 days
Secondary	Time-related valve safety at 1 year	Time-related valve safety	1 year
Secondary	Echocardiographic endpoint (1)	- Structural valve deterioration	Post-procedurally [day 1 to 7], at 30 days, 1 year
Secondary	Echocardiographic endpoint (2)	- Prosthetic aortic valve stenosis	Post-procedurally [day 1 to 7], at 30 days, 1 year
Secondary	Echocardiographic endpoint (3)	- Patient prosthesis mismatch	Post-procedurally [day 1 to 7], at 30 days, 1 year
Secondary	Echocardiographic endpoint (4)	- Aortic regurgitation (grading), proportion of more than mild regurgitation	Post-procedurally [day 1 to 7], at 30 days, 1 year
Secondary	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
Secondary	Echocardiographic endpoint (6)	- Systolic LV ejection fraction	Post-procedurally [day 1 to 7], at 30 days, 1 year
Secondary	Echocardiographic endpoint (7)	- LV diastolic function	Post-procedurally [day 1 to 7], at 30 days, 1 year
Secondary	Echocardiographic endpoint (8)	- Left atrial volume	Post-procedurally [day 1 to 7], at 30 days, 1 year
Secondary	Echocardiographic endpoint (9)	- Right ventricular (RV) dimension and function	Post-procedurally [day 1 to 7], at 30 days, 1 year
Secondary	Echocardiographic endpoint (10)	- Right atrial (RA) area	Post-procedurally [day 1 to 7], at 30 days, 1 year
Secondary	Echocardiographic endpoint (11)	- RV/RA-ratio and estimated systolic pulmonary arterial pressure	Post-procedurally [day 1 to 7], at 30 days, 1 year