The primary objective of this study (LANDMARK) is to compare the safety and effectiveness of the Myval THV Series with Contemporary Valves (Sapien THV Series and Evolut THV Series) in patients with severe symptomatic native aortic valve stenosis. This study will be done in total 768 subjects (384:384, Myval THV Series vs. Contemporary Valves) The randomisation will be carried out with an allocation ratio of 1:1 between Myval THV Series vs. Contemporary Valves (Sapien THV Series and Evolut THV Series)
LANDMARK Trial is a prospective, randomised, multinational, multicentric, open-label non-inferiority trial of total 768 subjects (384:384, Myval THV Series vs. Contemporary Valves) with severe symptomatic native aortic valve stenosis via transfemoral approach. * Device sizes applicable for the Myval THV Series: 20 mm, 21.5 mm, 23 mm, 24.5 mm, 26 mm, 27.5 mm, and 29 mm diameter. * Device sizes applicable for the Sapien 3 THV Series: 20 mm, 23 mm, 26 mm, and 29 mm diameter. * Device sizes applicable for the Evolut THV Series: 23 mm, 26 mm, 29 mm, and 34 mm diameter. A non-randomised nested registry will be conducted to include patients requiring extra-large size of Myval THV series (XL Nested Registry) \- Device sizes applicable for the XL Nested Registry: 30.5 mm and 32 mm. A non-randomized registry will include patients implanted with the Myval THV Series (Lead-in Set). \- The investigators have to perform a minimum of 2 lead-in cases (non-randomised) under the guidance of the lead-in evaluation committee.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
988
The devices in the study are intended to improve aortic valve function for patients with severe symptomatic native aortic valve stenosis who are eligible for TAVR therapy. Every patient must be deemed treatable with an available size of both the test and contemporary heart valves approved for use and commercially available at the investigational centre where the implant procedure is being performed.
The devices in the study are intended to improve aortic valve function for patients with severe symptomatic native aortic valve stenosis who are eligible for TAVR therapy. Every patient must be deemed treatable with an available size of both the test and contemporary heart valves approved for use and commercially available at the investigational centre where the implant procedure is being performed.
Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
It is the composite of following: * All-cause mortality * All stroke * Bleeding (Type 3 and 4) * Acute kidney injury (AKI) (Stage 2, 3 and 4) * Major vascular complications * Moderate or severe prosthetic valve regurgitation * Conduction system disturbances resulting in a new PPI
Time frame: 30-day
The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
It is the composite of following: * All-cause mortality * All stroke * Bleeding (Type 3 and 4) * AKI (Stage 2, 3 and 4) * Major vascular complications * Moderate or severe prosthetic valve regurgitation * Conduction system disturbances resulting in a new PPI
Time frame: 1-year
All-cause mortality
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4 year, 5-year, 7-year, and 10-year
All stroke
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Acute Kidney Injury (AKI) (Stage 2, 3 and 4)
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, and 1-year
Bleeding (Type 3 and 4)
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Moderate or severe prosthetic valve regurgitation
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Republican Scientific-Practical Centre "Cardiology"
Minsk, Belarus
NOT_YET_RECRUITINGHospital Dante Pazanesse
São Paulo, Brazil
RECRUITINGSplit Clinical Hospital Center
Split, Croatia
RECRUITINGUniversity Hospital Dubrava Avenija Gojka Šuška 6
Zagreb, Croatia
RECRUITINGNorth Estonia Medical Center
Tallinn, Estonia
RECRUITINGHôpital Henri Mondor
Créteil, France
RECRUITINGLille University
Lille, France
RECRUITINGInstitut Cardiovascular Paris-Sud
Massy, France
RECRUITINGArnault Tzanck Institute
Nice, France
RECRUITINGCentre Hospitalier Universitaire De Rennes
Rennes, France
NOT_YET_RECRUITING...and 44 more locations
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year
New permanent pacemaker implantation (As per VARC-3 defined criteria)
o New PPI rates will be analysed further based on the patient's history of left and/or right bundle branch block.
Time frame: Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4-year, 5-year, 7-year, and 10-year
Conduction disturbances and arrhythmias
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Device success
As per VARC-3 defined criteria
Time frame: Pre-discharge and 30-day
Early safety at 30 days
As per VARC-3 defined criteria
Time frame: 30-day
Clinical efficacy at 30 days
As per VARC-3 defined criteria
Time frame: After 30 days of index procedure
Valve related long-term clinical efficacy
As per VARC-3 defined criteria
Time frame: 5-years, 7 years and 10 years
Vascular and access related complications
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, and 1-year
Major vascular complications
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, and 1-year
Functional improvement from baseline as measured per
New York Heart Association (NYHA) functional classification \[Time frame: Baseline (pre-procedure), 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year\] Six-minute walk test \[Time frame: Baseline (pre-procedure), 30-day and 1-year\]
Time frame: [Time frame: Baseline (pre-procedure), 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year], [Time frame: Baseline (pre-procedure), 30-day and 1-year]
Echocardiographic endpoints
* Effective orifice area (EOA) * Index effective orifice area (iEOA) * Mean aortic valve gradient * Peak aortic valve gradient * Peak aortic velocity * Total aortic regurgitation, transvalvular regurgitation (except baseline) and paravalvular regurgitation (except baseline) * Left ventricular ejection fraction (LVEF) * Valve calcification * Cardiac output and cardiac index
Time frame: Baseline, pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year
Bioprosthetic valve deterioration
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Patient-prosthesis mismatch
Severity patient-prosthesis-mismatch will be based on following * For subjects with body mass index (BMI) \<30 kg/m2, EOAi: 0.85 - 0.66 cm2 /m2 considered as moderate and ≤0.65 cm2 /m2 considered as severe * For subjects with BMI ≥30 kg/m2, EOAi: 0.70 - 0.56 cm2 /m2 considered as moderate and ≤0.55 cm2 /m2 considered as severe * BMI = weight(kg)/(height (m))2
Time frame: Pre-discharge, 30-day, and 1-year
Length of index hospital stay
o Number of days from hospital admission to discharge.
Time frame: At discharge
Re-hospitalization
As per VARC-3 defined criteria
Time frame: 30-day, 1-year, 3-year, and 5-year
Health status as evaluated by Quality of Life questionnaires
o 12-Item Short Form Survey (SF-12)
Time frame: Baseline (pre-procedure), 30-day, and 1-year
Valve thrombosis
o Valve thrombosis as per VARC-2 is 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.
Time frame: 30-day, 1-year, 3-year, and 5-year
Coronary obstruction requiring intervention
As per VARC-3 defined criteria
Time frame: Pre-discharge
Valve malpositioning
As per VARC-3 defined criteria
Time frame: Pre-discharge
Conversion to open surgery
As per VARC-3 defined criteria
Time frame: Pre-discharge
Unplanned use of mechanical circulatory support (cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), transcatheter pumps or intra-aortic balloon pump (IABP)
As per VARC-3 defined criteria
Time frame: Pre-discharge
Implantation of multiple (>1) transcatheter valves during the index hospitalization
As per VARC-3 defined criteria
Time frame: Index-procedure
Cardiac structural complications
As per VARC-3 defined criteria
Time frame: 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Ventricular septal perforation
o Angiographic or echocardiographic evidence of a new septal perforation during or after the TAVI procedure
Time frame: Pre-discharge
New onset of atrial fibrillation or atrial flutter
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Technical success
As per VARC-3 defined criteria
Time frame: Post-procedure
Myocardial Infarction
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Endocarditis
As per VARC-3 defined criteria
Time frame: 30-day, 1-year, 3-year, and 5-year