LANDMARK Trial: a Randomised Controlled Trial of Myval THV
- Conditions
- Aortic Valve Stenosis
- Interventions
- Device: Myval THV SeriesDevice: Contemporary Valves (Sapien THV Series and Evolut THV Series)
- Registration Number
- NCT04275726
- Lead Sponsor
- Meril Life Sciences Pvt. Ltd.
- 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)
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 988
- Patient ≥18 years of age.
- 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.
- As per local Heart Team assessment, patient is eligible for TAVI and the patient is suitable for implantation with all three study devices.
- Patients who are not willing to provide informed consent form, or whose legal heirs object to their participation in the study.
- Any condition, which in the Investigator's opinion, would preclude safe participation of patient in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Myval THV Series 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. Contemporary Valves Contemporary Valves (Sapien THV Series and Evolut THV Series) * 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.
- Primary Outcome Measures
Name Time Method Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3) 30-day 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
- Secondary Outcome Measures
Name Time Method Major vascular complications Pre-discharge, 30-day, and 1-year As per VARC-3 defined criteria
Bleeding (Type 3 and 4) Pre-discharge, 30-day, 1-year, 3-year, and 5-year As per VARC-3 defined criteria
Device success Pre-discharge and 30-day As per VARC-3 defined criteria
Clinical efficacy at 30 days After 30 days of index procedure As per VARC-3 defined criteria
The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3) 1-year 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 PPIAll stroke Pre-discharge, 30-day, 1-year, 3-year, and 5-year As per VARC-3 defined criteria
Acute Kidney Injury (AKI) (Stage 2, 3 and 4) Pre-discharge, 30-day, and 1-year As per VARC-3 defined criteria
Valve related long-term clinical efficacy 5-years, 7 years and 10 years As per VARC-3 defined criteria
Vascular and access related complications Pre-discharge, 30-day, and 1-year As per VARC-3 defined criteria
Functional improvement from baseline as measured per [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] 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 \[Time frame: Baseline (pre-procedure), 30-day and 1-year\]
Re-hospitalization 30-day, 1-year, 3-year, and 5-year As per VARC-3 defined criteria
Valve thrombosis 30-day, 1-year, 3-year, and 5-year 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.
Conversion to open surgery Pre-discharge As per VARC-3 defined criteria
Implantation of multiple (>1) transcatheter valves during the index hospitalization Index-procedure As per VARC-3 defined criteria
Cardiac structural complications 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years As per VARC-3 defined criteria
Myocardial Infarction Pre-discharge, 30-day, 1-year, 3-year, and 5-year As per VARC-3 defined criteria
Early safety at 30 days 30-day As per VARC-3 defined criteria
Coronary obstruction requiring intervention Pre-discharge As per VARC-3 defined criteria
All-cause mortality Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4 year, 5-year, 7-year, and 10-year As per VARC-3 defined criteria
Moderate or severe prosthetic valve regurgitation Pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year As per VARC-3 defined criteria
New permanent pacemaker implantation (As per VARC-3 defined criteria) Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4-year, 5-year, 7-year, and 10-year o New PPI rates will be analysed further based on the patient's history of left and/or right bundle branch block.
Conduction disturbances and arrhythmias Pre-discharge, 30-day, 1-year, 3-year, and 5-year As per VARC-3 defined criteria
Echocardiographic endpoints Baseline, pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year * 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 indexLength of index hospital stay At discharge o Number of days from hospital admission to discharge.
Health status as evaluated by Quality of Life questionnaires Baseline (pre-procedure), 30-day, and 1-year o 12-Item Short Form Survey (SF-12)
Valve malpositioning Pre-discharge As per VARC-3 defined criteria
Unplanned use of mechanical circulatory support (cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), transcatheter pumps or intra-aortic balloon pump (IABP) Pre-discharge As per VARC-3 defined criteria
Technical success Post-procedure As per VARC-3 defined criteria
Endocarditis 30-day, 1-year, 3-year, and 5-year As per VARC-3 defined criteria
Bioprosthetic valve deterioration Pre-discharge, 30-day, 1-year, 3-year, and 5-year As per VARC-3 defined criteria
Patient-prosthesis mismatch Pre-discharge, 30-day, and 1-year 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))2Ventricular septal perforation Pre-discharge o Angiographic or echocardiographic evidence of a new septal perforation during or after the TAVI procedure
New onset of atrial fibrillation or atrial flutter Pre-discharge, 30-day, 1-year, 3-year, and 5-year As per VARC-3 defined criteria
Trial Locations
- Locations (54)
Republican Scientific-Practical Centre "Cardiology"
🇧🇾Minsk, Belarus
Hospital Dante Pazanesse
🇧🇷São Paulo, Brazil
Split Clinical Hospital Center
🇭🇷Split, Croatia
University Hospital Dubrava Avenija Gojka Šuška 6
🇭🇷Zagreb, Croatia
North Estonia Medical Center
🇪🇪Tallinn, Estonia
Hôpital Henri Mondor
🇫🇷Créteil, France
Lille University
🇫🇷Lille, France
Institut Cardiovascular Paris-Sud
🇫🇷Massy, France
Arnault Tzanck Institute
🇫🇷Nice, France
Centre Hospitalier Universitaire De Rennes
🇫🇷Rennes, France
Kerckhoff-KlinikForschungs GmbH
🇩🇪Bad Nauheim, Hesse, Germany
Leipzig Heart Institute GmbH
🇩🇪Leipzig, Saxony, Germany
University Herzentrum Division of Cardiology and Angiology II,University Heart Center Freiburg, Südring 15
🇩🇪Bad Krozingen, Germany
Klinikum Braunschweig Freisestre
🇩🇪Braunschweig, Germany
Technology University Dresden Fetscherstraße 76
🇩🇪Dresden, Germany
Asklepios Kliniken Hamburg Gmbh Lohmuehlenstrasse 5
🇩🇪Hamburg, Germany
Klinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
Hippkration Hospital
🇬🇷Athens, Greece
Hygeia hospital
🇬🇷Maroúsi, Greece
Interbalkan European Medical Center
🇬🇷Thessaloniki, Greece
Semmelweis University
🇭🇺Budapest, Hungary
University of Bologna Policlinico S. Orsola-Malpigh
🇮🇹Bologna, Italy
Policlinico di Catania
🇮🇹Catania, Italy
San Raffaele Hospital
🇮🇹Milano, Italy
Clinical Institute Saint Ambrogio
🇮🇹Milano, Italy
San Donato Hospital
🇮🇹Milan, Italy
Mauriliano Hospital Largo Filippo
🇮🇹Tortona, Italy
University Hospital Città della Salute e della Scienza Turin Bramante
🇮🇹Turin, Italy
St Antonius Hospital
🇳🇱Nieuwegein, Dutch, Netherlands
Radboud University Nijmegen
🇳🇱Nijmegen, Gelderland, Netherlands
Isala Zwolle Hospital
🇳🇱Zwolle, Overijssel, Netherlands
Onze lieve vrouwe gasthuis Oosterperk 9
🇳🇱Amsterdam, Netherlands
Amphia Ziekenhui Hospital
🇳🇱Breda, Netherlands
University Medical Center (UMC)
🇳🇱Groningen, Netherlands
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands
Auckland City Hospital 2 Park Road
🇳🇿Grafton, Auckland, New Zealand
John Paul II Hospital
🇵🇱Krakow, Małopolskie Województwo, Poland
University of Gdansk
🇵🇱Gdańsk, Pomorskie Województwo, Poland
Medical University of Silesia
🇵🇱Katowice, Prussian, Poland
Institute of Cardiology
🇵🇱Warsaw, Poland
Uniwersytecki Szpital Kliniczny (USK) Curie-Skłodowskiej 58
🇵🇱Wrocław, Poland
Centro Hospitalar Lisboa Ocidental EPE- Hospital Santa Cruz, Av. Prof. Dr. Reinaldo dos Santos
🇵🇹Carnaxide, Portugal
Hospital de Santa Maria, Av. Prof. Egas Moniz MB
🇵🇹Lisboa, Portugal
Centro Hospital Lisboa Central E.P.E. - Santa Marta
🇵🇹Lisbon, Portugal
Centro Hospitalar de Sao Joao
🇵🇹Porto, Portugal
University hospital Banska Bystrica Námestie Ludvíka Svobodu 1
🇸🇰Banská Bystrica, Slovakia
University Medical Center, Ljubljana
🇸🇮Ljubljana, Slovenia
Hospital Universitario de Gran Canaria Dr Negrin
🇪🇸Las Palmas, Canary Islands, Spain
Hospital Universitari Son Espases Carretera de Valldemossa
🇪🇸Palma De Mallorca, Illes Balears, Spain
Hospital Universitario Renei Sofia
🇪🇸Córdoba, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Cliinico Univertistario de Valladolid
🇪🇸Valladolid, Spain
Sahlgrenska University Hospital
🇸🇪Göteborg, Sweden
Uppsala University Hospital
🇸🇪Uppsala, Sweden