LANDMARK Trial: a Randomised Controlled Trial of Myval THV (LANDMARK)

March 14, 2024 updated by: Meril Life Sciences Pvt. Ltd.

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

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)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

768

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belarus
      • Minsk, Belarus, 220036
        • Not yet recruiting
        • Republican Scientific-Practical Centre "Cardiology"
        • Contact:
  • Brazil
      • São Paulo, Brazil, 04012-909
        • Recruiting
        • Hospital Dante Pazanesse
        • Contact:
        • Sub-Investigator:
          • Andrea Vilela,
        • Sub-Investigator:
          • Dimytri Siqueira
  • Croatia
      • Split, Croatia, 21000
      • Zagreb, Croatia, 10000
        • Recruiting
        • University Hospital Dubrava Avenija Gojka Šuška 6
        • Contact:
          • Dr. Daniel Unić, MD
          • Phone Number: +385989196621
          • Email: unic@kbd.hr
  • Estonia
      • Tallinn, Estonia
        • Recruiting
        • North Estonia Medical Center
        • Contact:
          • Dr. Peep Laanmets
  • France
      • Créteil, France, 94000
      • Lille, France, 59000
      • Massy, France, 91300
        • Recruiting
        • Institut Cardiovascular Paris-Sud
        • Contact:
      • Nice, France, 06200
      • Rennes, France, 35033
  • Germany
      • Bad Krozingen, Germany, 79189
        • Recruiting
        • University Herzentrum Division of Cardiology and Angiology II,University Heart Center Freiburg, Südring 15
        • Contact:
      • Braunschweig, Germany, 38118
        • Active, not recruiting
        • Klinikum Braunschweig Freisestre
      • Dresden, Germany, 01307
      • Hamburg, Germany, 20099
      • Regensburg, Germany, 93053
        • Recruiting
        • Klinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg
        • Contact:
        • Sub-Investigator:
          • Prof. Dr. Med. Michael Hilker
    • Hesse
      • Bad Nauheim, Hesse, Germany, 61231
        • Recruiting
        • Kerckhoff-KlinikForschungs GmbH
        • Contact:
    • Saxony
  • Greece
      • Athens, Greece, 11527
        • Recruiting
        • Hippkration Hospital
        • Contact:
      • Maroúsi, Greece
      • Thessaloniki, Greece, 555 35
        • Recruiting
        • Interbalkan European Medical Center
        • Contact:
  • Hungary
      • Budapest, Hungary, 1122
        • Recruiting
        • Semmelweis University
        • Contact:
        • Sub-Investigator:
          • Dr. Roland Papp, MD
  • Italy
      • Bologna, Italy, 40141
        • Not yet recruiting
        • University of Bologna Policlinico S. Orsola-Malpigh
        • Contact:
      • Catania, Italy, 95100
        • Not yet recruiting
        • Policlinico di Catania
        • Contact:
      • Milan, Italy, 20121-20162
      • Milano, Italy, 20149
        • Recruiting
        • Clinical Institute Saint Ambrogio
        • Contact:
      • Milano, Italy, 20132
        • Recruiting
        • San Raffaele Hospital
        • Contact:
        • Sub-Investigator:
          • Dr.BELLINI BARBARA
      • Tortona, Italy, 10128
        • Not yet recruiting
        • Mauriliano Hospital Largo Filippo
        • Contact:
          • Prof. Dr. Giuseppe Musumeci
      • Turin, Italy, 10126
        • Not yet recruiting
        • University Hospital Città della Salute e della Scienza Turin Bramante
        • Contact:
  • Netherlands
      • Amsterdam, Netherlands, 1091
        • Active, not recruiting
        • Onze lieve vrouwe gasthuis Oosterperk 9
      • Breda, Netherlands, 4817
        • Recruiting
        • Amphia Ziekenhui Hospital
        • Contact:
      • Groningen, Netherlands, 9713
      • Utrecht, Netherlands, 3584
    • Dutch
      • Nieuwegein, Dutch, Netherlands, 3435
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525 XZ
    • Overijssel
      • Zwolle, Overijssel, Netherlands, 8025 AB
        • Active, not recruiting
        • Isala Zwolle Hospital
  • New Zealand
    • Auckland
      • Grafton, Auckland, New Zealand, 1023
        • Recruiting
        • Auckland City Hospital 2 Park Road
        • Contact:
  • Poland
      • Warsaw, Poland, 50-013
        • Not yet recruiting
        • Institute of Cardiology
        • Contact:
          • Prof. Adam Witkowski, MD, PhD, FESC
          • Phone Number: +48 22 812 41 64
          • Email: witkowski@hbz.pl
      • Wrocław, Poland, 50-369
        • Recruiting
        • Uniwersytecki Szpital Kliniczny (USK) Curie-Skłodowskiej 58
        • Contact:
    • Małopolskie Województwo
      • Krakow, Małopolskie Województwo, Poland, 31-202
        • Not yet recruiting
        • John Paul II Hospital
        • Contact:
          • Dr n. med Jaroslaw Trebacz, MD PhD
    • Pomorskie Województwo
      • Gdańsk, Pomorskie Województwo, Poland, 80-952
        • Not yet recruiting
        • University of Gdansk
        • Contact:
        • Sub-Investigator:
          • Radoslaw Targonski, MD PhD
        • Sub-Investigator:
          • Aleksandra Wierzbowska, MD
        • Sub-Investigator:
          • Marcin Fijalkowski, PhD
    • Prussian
      • Katowice, Prussian, Poland, 40-635
        • Not yet recruiting
        • Medical University of Silesia
        • Contact:
  • Portugal
      • Carnaxide, Portugal, 2790-134
        • Recruiting
        • Centro Hospitalar Lisboa Ocidental EPE- Hospital Santa Cruz, Av. Prof. Dr. Reinaldo dos Santos
        • Contact:
      • Lisboa, Portugal, 1649-028
        • Not yet recruiting
        • Hospital de Santa Maria, Av. Prof. Egas Moniz MB
        • Contact:
      • Lisbon, Portugal, 1169-024
        • Recruiting
        • Centro Hospital Lisboa Central E.P.E. - Santa Marta
        • Contact:
      • Porto, Portugal, 4200-319
        • Not yet recruiting
        • Centro Hospitalar de São João
        • Contact:
  • Slovakia
      • Banská Bystrica, Slovakia, 975 17
        • Recruiting
        • University hospital Banska Bystrica Námestie Ludvíka Svobodu 1
        • Contact:
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Recruiting
        • University Medical Center, Ljubljana
        • Contact:
  • Spain
      • Córdoba, Spain, 5000
      • Madrid, Spain, 28040
        • Not yet recruiting
        • Hospital Clinico San Carlos
        • Contact:
      • Valladolid, Spain, 47003
        • Recruiting
        • Hospital Cliinico Univertistario de Valladolid
        • Contact:
          • Dr. Ignacio A Santos, Medicine & Surgery
          • Phone Number: +34657923040
          • Email: ijamat@gmail.com
        • Sub-Investigator:
          • Dr. Juan Pablo Sánchez Luna, MD, PhD
    • Canary Islands
      • Las Palmas, Canary Islands, Spain, 35010
        • Recruiting
        • Hospital Universitario de Gran Canaria Dr Negrin
        • Contact:
    • Illes Balears
      • Palma De Mallorca, Illes Balears, Spain, 07120
        • Recruiting
        • Hospital Universitari Son Espases Carretera de Valldemossa
        • Contact:
        • Sub-Investigator:
          • Dr. Tania Rdgz Gabella
  • Sweden
      • Göteborg, Sweden
      • Uppsala, Sweden

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Device: 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.
Other Names:
  • Myval/Myval Inception THVs or any subsequent advanced version commercially available at the study site.
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.
Device: 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.
Other Names:
  • Sapien THV Series (Sapien 3/Sapien 3 Ultra THVs) and Evolut THV Series (Evolut R/Evolut PRO THVs ) or any subsequent advanced version commercially available at the study site.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
Time Frame: 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
30-day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional improvement from baseline as measured per
Time Frame: Baseline (within 30 days prior to index procedure), 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year)
New York Heart Association (NYHA) functional classification
Baseline (within 30 days prior to index procedure), 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year)
The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
Time Frame: 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 PPI
1-year
All-cause mortality
Time Frame: 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
Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4 year, 5-year, 7-year, and 10-year
All stroke
Time Frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
As per VARC-3 defined criteria
Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Acute Kidney Injury (AKI) (Stage 2, 3 and 4)
Time Frame: Pre-discharge, 30-day, and 1-year
As per VARC-3 defined criteria
Pre-discharge, 30-day, and 1-year
Bleeding (Type 3 and 4)
Time Frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
As per VARC-3 defined criteria
Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Moderate or severe prosthetic valve regurgitation
Time Frame: Pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year
As per VARC-3 defined criteria
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)
Time Frame: 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.
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
Time Frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
As per VARC-3 defined criteria
Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Device success
Time Frame: Pre-discharge and 30-day
As per VARC-3 defined criteria
Pre-discharge and 30-day
Early safety at 30 days
Time Frame: 30-day
As per VARC-3 defined criteria
30-day
Clinical efficacy at 30 days
Time Frame: After 30 days of index procedure
As per VARC-3 defined criteria
After 30 days of index procedure
Valve related long-term clinical efficacy
Time Frame: 5-years, 7 years and 10 years
As per VARC-3 defined criteria
5-years, 7 years and 10 years
Vascular and access related complications
Time Frame: Pre-discharge, 30-day, and 1-year
As per VARC-3 defined criteria
Pre-discharge, 30-day, and 1-year
Major vascular complications
Time Frame: Pre-discharge, 30-day, and 1-year
As per VARC-3 defined criteria
Pre-discharge, 30-day, and 1-year
Functional improvement from baseline as measured per
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]
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: 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
Time Frame: 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 index
Baseline, pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year
Bioprosthetic valve deterioration
Time Frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
As per VARC-3 defined criteria
Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Patient-prosthesis mismatch
Time Frame: 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))2
Pre-discharge, 30-day, and 1-year
Length of index hospital stay
Time Frame: At discharge
o Number of days from hospital admission to discharge.
At discharge
Re-hospitalization
Time Frame: 30-day, 1-year, 3-year, and 5-year
As per VARC-3 defined criteria
30-day, 1-year, 3-year, and 5-year
Health status as evaluated by Quality of Life questionnaires
Time Frame: Baseline (pre-procedure), 30-day, and 1-year
o 12-Item Short Form Survey (SF-12)
Baseline (pre-procedure), 30-day, and 1-year
Valve thrombosis
Time Frame: 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.
30-day, 1-year, 3-year, and 5-year
Coronary obstruction requiring intervention
Time Frame: Pre-discharge
As per VARC-3 defined criteria
Pre-discharge
Valve malpositioning
Time Frame: Pre-discharge
As per VARC-3 defined criteria
Pre-discharge
Conversion to open surgery
Time Frame: Pre-discharge
As per VARC-3 defined criteria
Pre-discharge
Unplanned use of mechanical circulatory support (cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), transcatheter pumps or intra-aortic balloon pump (IABP)
Time Frame: Pre-discharge
As per VARC-3 defined criteria
Pre-discharge
Implantation of multiple (>1) transcatheter valves during the index hospitalization
Time Frame: Index-procedure
As per VARC-3 defined criteria
Index-procedure
Cardiac structural complications
Time Frame: 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
As per VARC-3 defined criteria
30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Ventricular septal perforation
Time Frame: Pre-discharge
o Angiographic or echocardiographic evidence of a new septal perforation during or after the TAVI procedure
Pre-discharge
New onset of atrial fibrillation or atrial flutter
Time Frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
As per VARC-3 defined criteria
Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Technical success
Time Frame: Post-procedure
As per VARC-3 defined criteria
Post-procedure
Myocardial Infarction
Time Frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
As per VARC-3 defined criteria
Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Endocarditis
Time Frame: 30-day, 1-year, 3-year, and 5-year
As per VARC-3 defined criteria
30-day, 1-year, 3-year, and 5-year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Meril Life Sciences Pvt. Ltd.

Investigators

  • Study Chair: Andreas Baumbach, MD,FESC,FRCP, Barts Heart Center, London, UK
  • Study Director: Patrick W. Serruys, MD,PhD,FACC,FESC, National University of Ireland, Galway, Ireland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 4, 2020

Primary Completion (Actual)

March 7, 2024

Study Completion (Estimated)

December 31, 2033

Study Registration Dates

First Submitted

February 4, 2020

First Submitted That Met QC Criteria

February 17, 2020

First Posted (Actual)

February 19, 2020

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 14, 2024

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MLS/MYV-2/LANDMARK
  • 2020-000137-40 (EudraCT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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