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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04275726
Registration number
NCT04275726
Ethics application status
Date submitted
4/02/2020
Date registered
19/02/2020
Titles & IDs
Public title
LANDMARK Trial: a Randomised Controlled Trial of Myval THV
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Scientific title
A Prospective, Multinational, Multicentre, Open-label, Randomised, Non-inferiority Trial to Compare Safety and Effectiveness of Meril's Myval Transcatheter Heart Valve (THV) Series vs. Contemporary Valves (Edwards's Sapien THV Series and Medtronic's Evolut THV Series) in Patients With Severe Symptomatic Native Aortic Valve Stenosis
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Secondary ID [1]
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2020-000137-40
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Secondary ID [2]
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MLS/MYV-2/LANDMARK
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Universal Trial Number (UTN)
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Trial acronym
LANDMARK
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Aortic Valve Stenosis
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Condition category
Condition code
Cardiovascular
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Diseases of the vasculature and circulation including the lymphatic system
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Other
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Research that is not of generic health relevance and not applicable to specific health categories listed above
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Devices - Myval THV Series
Treatment: Devices - Contemporary Valves (Sapien THV Series and Evolut THV Series)
Experimental: Myval THV Series - Myval THV Series will include Myval/Myval Inception THVs or any subsequent advanced version commercially available at the study site.
This treatment arm will be assigned to 384 / 768 subjects enrolled in a study.
Active comparator: Contemporary Valves - * Sapien THV Series will consist of Sapien 3/Sapien 3 Ultra THVs or any subsequent advanced version commercially available at the study site.
* Evolut THV Series will include Evolut R/Evolut PRO THVs or any subsequent advanced version commercially available at the study site.
This treatment arm will be assigned to 384 / 768 subjects enrolled in a study.
Treatment: Devices: Myval THV Series
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.
Treatment: Devices: Contemporary Valves (Sapien THV Series and Evolut THV Series)
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.
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Intervention code [1]
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Treatment: Devices
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
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Assessment method [1]
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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
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Timepoint [1]
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30-day
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Secondary outcome [1]
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The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
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Assessment method [1]
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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
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Timepoint [1]
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1-year
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Secondary outcome [2]
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All-cause mortality
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Assessment method [2]
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As per VARC-3 defined criteria
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Timepoint [2]
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Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4 year, 5-year, 7-year, and 10-year
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Secondary outcome [3]
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All stroke
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Assessment method [3]
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As per VARC-3 defined criteria
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Timepoint [3]
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Pre-discharge, 30-day, 1-year, 3-year, and 5-year
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Secondary outcome [4]
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Acute Kidney Injury (AKI) (Stage 2, 3 and 4)
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Assessment method [4]
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As per VARC-3 defined criteria
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Timepoint [4]
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Pre-discharge, 30-day, and 1-year
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Secondary outcome [5]
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Bleeding (Type 3 and 4)
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Assessment method [5]
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0
As per VARC-3 defined criteria
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Timepoint [5]
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Pre-discharge, 30-day, 1-year, 3-year, and 5-year
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Secondary outcome [6]
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Moderate or severe prosthetic valve regurgitation
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Assessment method [6]
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As per VARC-3 defined criteria
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Timepoint [6]
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Pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year
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Secondary outcome [7]
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New permanent pacemaker implantation (As per VARC-3 defined criteria)
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Assessment method [7]
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o New PPI rates will be analysed further based on the patient's history of left and/or right bundle branch block.
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Timepoint [7]
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Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4-year, 5-year, 7-year, and 10-year
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Secondary outcome [8]
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Conduction disturbances and arrhythmias
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Assessment method [8]
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0
As per VARC-3 defined criteria
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Timepoint [8]
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Pre-discharge, 30-day, 1-year, 3-year, and 5-year
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Secondary outcome [9]
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Device success
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Assessment method [9]
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0
As per VARC-3 defined criteria
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Timepoint [9]
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Pre-discharge and 30-day
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Secondary outcome [10]
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Early safety at 30 days
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Assessment method [10]
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As per VARC-3 defined criteria
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Timepoint [10]
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30-day
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Secondary outcome [11]
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Clinical efficacy at 30 days
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Assessment method [11]
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As per VARC-3 defined criteria
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Timepoint [11]
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After 30 days of index procedure
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Secondary outcome [12]
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Valve related long-term clinical efficacy
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Assessment method [12]
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As per VARC-3 defined criteria
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Timepoint [12]
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5-years, 7 years and 10 years
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Secondary outcome [13]
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Vascular and access related complications
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Assessment method [13]
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0
As per VARC-3 defined criteria
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Timepoint [13]
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Pre-discharge, 30-day, and 1-year
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Secondary outcome [14]
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Major vascular complications
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Assessment method [14]
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0
As per VARC-3 defined criteria
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Timepoint [14]
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Pre-discharge, 30-day, and 1-year
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Secondary outcome [15]
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Functional improvement from baseline as measured per
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Assessment method [15]
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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 \[Time frame: Baseline (pre-procedure), 30-day and 1-year\]
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Timepoint [15]
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[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]
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Secondary outcome [16]
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Echocardiographic endpoints
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Assessment method [16]
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* 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
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Timepoint [16]
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Baseline, pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year
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Secondary outcome [17]
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Bioprosthetic valve deterioration
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Assessment method [17]
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As per VARC-3 defined criteria
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Timepoint [17]
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Pre-discharge, 30-day, 1-year, 3-year, and 5-year
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Secondary outcome [18]
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Patient-prosthesis mismatch
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Assessment method [18]
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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
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Timepoint [18]
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Pre-discharge, 30-day, and 1-year
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Secondary outcome [19]
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Length of index hospital stay
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Assessment method [19]
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o Number of days from hospital admission to discharge.
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Timepoint [19]
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At discharge
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Secondary outcome [20]
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Re-hospitalization
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Assessment method [20]
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As per VARC-3 defined criteria
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Timepoint [20]
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30-day, 1-year, 3-year, and 5-year
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Secondary outcome [21]
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Health status as evaluated by Quality of Life questionnaires
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Assessment method [21]
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o 12-Item Short Form Survey (SF-12)
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Timepoint [21]
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Baseline (pre-procedure), 30-day, and 1-year
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Secondary outcome [22]
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Valve thrombosis
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Assessment method [22]
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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.
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Timepoint [22]
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30-day, 1-year, 3-year, and 5-year
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Secondary outcome [23]
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Coronary obstruction requiring intervention
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Assessment method [23]
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0
As per VARC-3 defined criteria
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Timepoint [23]
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0
Pre-discharge
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Secondary outcome [24]
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Valve malpositioning
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Assessment method [24]
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As per VARC-3 defined criteria
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Timepoint [24]
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Pre-discharge
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Secondary outcome [25]
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Conversion to open surgery
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Assessment method [25]
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0
As per VARC-3 defined criteria
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Timepoint [25]
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0
Pre-discharge
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Secondary outcome [26]
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Unplanned use of mechanical circulatory support (cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), transcatheter pumps or intra-aortic balloon pump (IABP)
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Assessment method [26]
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0
As per VARC-3 defined criteria
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Timepoint [26]
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Pre-discharge
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Secondary outcome [27]
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Implantation of multiple (>1) transcatheter valves during the index hospitalization
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Assessment method [27]
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As per VARC-3 defined criteria
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Timepoint [27]
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Index-procedure
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Secondary outcome [28]
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Cardiac structural complications
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Assessment method [28]
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As per VARC-3 defined criteria
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Timepoint [28]
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30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
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Secondary outcome [29]
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Ventricular septal perforation
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Assessment method [29]
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o Angiographic or echocardiographic evidence of a new septal perforation during or after the TAVI procedure
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Timepoint [29]
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Pre-discharge
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Secondary outcome [30]
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New onset of atrial fibrillation or atrial flutter
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Assessment method [30]
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As per VARC-3 defined criteria
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Timepoint [30]
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Pre-discharge, 30-day, 1-year, 3-year, and 5-year
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Secondary outcome [31]
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Technical success
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Assessment method [31]
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0
As per VARC-3 defined criteria
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Timepoint [31]
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Post-procedure
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Secondary outcome [32]
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0
Myocardial Infarction
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Assessment method [32]
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0
As per VARC-3 defined criteria
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Timepoint [32]
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Pre-discharge, 30-day, 1-year, 3-year, and 5-year
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Secondary outcome [33]
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Endocarditis
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Assessment method [33]
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As per VARC-3 defined criteria
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Timepoint [33]
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30-day, 1-year, 3-year, and 5-year
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Eligibility
Key inclusion criteria
1. Patient =18 years of age.
2. Patient or their legal representative has provided written informed consent as approved by the Institutional Review Board (IRB)/Institutional Ethics Committee (IEC) of the investigational site to participate in the study.
3. As per local Heart Team assessment, patient is eligible for TAVI and the patient is suitable for implantation with all three study devices.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Patients who are not willing to provide informed consent form, or whose legal heirs object to their participation in the study.
2. Any condition, which in the Investigator's opinion, would preclude safe participation of patient in the study.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
NA
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
4/11/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
31/12/2033
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Actual
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Sample size
Target
768
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
Country [1]
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Belarus
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State/province [1]
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Minsk
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Brazil
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State/province [2]
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São Paulo
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Croatia
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State/province [3]
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Split
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Croatia
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Zagreb
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Estonia
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State/province [5]
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Tallinn
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France
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State/province [6]
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Créteil
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Country [7]
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France
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State/province [7]
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Lille
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Country [8]
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France
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State/province [8]
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Massy
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Country [9]
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France
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State/province [9]
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Nice
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Country [10]
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France
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State/province [10]
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Rennes
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Country [11]
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Germany
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State/province [11]
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Hesse
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Country [12]
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Germany
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State/province [12]
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Saxony
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Country [13]
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Germany
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State/province [13]
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Bad Krozingen
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Country [14]
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Germany
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State/province [14]
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Braunschweig
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Country [15]
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Germany
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State/province [15]
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Dresden
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Country [16]
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Germany
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State/province [16]
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Hamburg
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Country [17]
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Germany
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State/province [17]
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Regensburg
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Country [18]
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Greece
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State/province [18]
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Athens
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Country [19]
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Greece
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State/province [19]
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Maroúsi
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Greece
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State/province [20]
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Thessaloniki
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Country [21]
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Hungary
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State/province [21]
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Budapest
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Country [22]
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Italy
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State/province [22]
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Bologna
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Country [23]
0
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Italy
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State/province [23]
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Catania
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Country [24]
0
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Italy
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State/province [24]
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Milano
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Country [25]
0
0
Italy
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State/province [25]
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Milan
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Country [26]
0
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Italy
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State/province [26]
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Tortona
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Country [27]
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Italy
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State/province [27]
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Turin
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Country [28]
0
0
Netherlands
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State/province [28]
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Dutch
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Country [29]
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0
Netherlands
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State/province [29]
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0
Gelderland
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Country [30]
0
0
Netherlands
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State/province [30]
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0
Overijssel
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Country [31]
0
0
Netherlands
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State/province [31]
0
0
Amsterdam
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Country [32]
0
0
Netherlands
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State/province [32]
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0
Breda
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Country [33]
0
0
Netherlands
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State/province [33]
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Groningen
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Country [34]
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0
Netherlands
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State/province [34]
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Utrecht
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Country [35]
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New Zealand
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Auckland
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Poland
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Malopolskie Województwo
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Poland
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Pomorskie Województwo
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0
0
Poland
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0
Prussian
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Poland
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State/province [39]
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Warsaw
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Poland
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State/province [40]
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Wroclaw
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0
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Portugal
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State/province [41]
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Carnaxide
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0
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Portugal
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State/province [42]
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Lisboa
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0
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Portugal
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State/province [43]
0
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Lisbon
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0
0
Portugal
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State/province [44]
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Porto
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Country [45]
0
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Slovakia
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State/province [45]
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Banská Bystrica
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0
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Slovenia
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State/province [46]
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0
Ljubljana
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0
0
Spain
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State/province [47]
0
0
Canary Islands
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Country [48]
0
0
Spain
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State/province [48]
0
0
Illes Balears
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Country [49]
0
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Spain
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State/province [49]
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0
Córdoba
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0
0
Spain
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Madrid
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Country [51]
0
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Spain
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State/province [51]
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Valladolid
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Country [52]
0
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Sweden
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State/province [52]
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Göteborg
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Country [53]
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Sweden
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State/province [53]
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Uppsala
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Meril Life Sciences Pvt. Ltd.
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
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)
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Trial website
https://clinicaltrials.gov/study/NCT04275726
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Trial related presentations / publications
Kawashima H, Soliman O, Wang R, Ono M, Hara H, Gao C, Zeller E, Thakkar A, Tamburino C, Bedogni F, Neumann FJ, Thiele H, Abdel-Wahab M, Morice MC, Webster M, Rosseel L, Mylotte D, Onuma Y, Wijns W, Baumbach A, Serruys PW. Rationale and design of a randomized clinical trial comparing safety and efficacy of myval transcatheter heart valve versus contemporary transcatheter heart valves in patients with severe symptomatic aortic valve stenosis: The LANDMARK trial. Am Heart J. 2021 Feb;232:23-38. doi: 10.1016/j.ahj.2020.11.001. Epub 2020 Nov 6. Kawashima H, Wang R, Mylotte D, Jagielak D, De Marco F, Ielasi A, Onuma Y, den Heijer P, Terkelsen CJ, Wijns W, Serruys PW, Soliman O. Quantitative Angiographic Assessment of Aortic Regurgitation after Transcatheter Aortic Valve Implantation among Three Balloon-Expandable Valves. Glob Heart. 2021 Mar 19;16(1):20. doi: 10.5334/gh.959.
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Public notes
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Contacts
Principal investigator
Name
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0
Andreas Baumbach, MD,FESC,FRCP
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Address
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0
Barts Heart Center, London, UK
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Contact person for public queries
Name
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Ashok Thakkar, PhD
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Address
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+91-9879443584
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[email protected]
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04275726