LANDMARK Trial: a Randomised Controlled Trial of Myval THV

NCT04275726 | Recruiting DMC

• 2 other identifiers: MLS/MYV-2/LANDMARK2020-000137-40
• Study Type: interventional
• Target: 988
• Locations: 15 countries
• Sites: 52

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)

Conditions

Aortic Valve Stenosis

Keywords

LANDMARK Trial; Trial to evaluate safety & effectiveness of Myval THV; CE Approved Myval THV Series

Outcome Measures

Primary Outcomes (1)

• 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

  30-day

Secondary Outcomes (33)

• The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)

  1-year

• All-cause mortality

  Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4 year, 5-year, 7-year, and 10-year

• All stroke

  Pre-discharge, 30-day, 1-year, 3-year, and 5-year

• Acute Kidney Injury (AKI) (Stage 2, 3 and 4)

  Pre-discharge, 30-day, and 1-year

• Bleeding (Type 3 and 4)

  Pre-discharge, 30-day, 1-year, 3-year, and 5-year

Study Arms (4)

Myval THV Series

EXPERIMENTAL

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

Contemporary Valves

ACTIVE COMPARATOR

* 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)

Myval THV Series XL Nested Registry

EXPERIMENTAL

A non-randomised, nested registry of patients with anatomy of native aortic annulus suitable to be implanted with extra-large size of Myval THV series (30.5mm or 32mm) as per Heart Team assessment/Investigator's discretion is designed. The objective of this registry is to assess the safety and effectiveness of extra-large sizes of Myval THV series. Approximately 100 patients will be recruited from approximately 30 participating centres in LANDMARK Trial

Device: Myval THV Series

Myval THV Series Lead-in Set

EXPERIMENTAL

The Lead-in Set aims to ensure investigators adhere to protocol requirements related to the Myval THV Series device, including imaging and procedural guidelines. Investigators should be independent before enrolling study subjects, allowing for valuable feedback for initial safety assessments. Each investigator must conduct at least two non-randomized lead-in cases under the guidance of an evaluation committee. Lead-in subjects will only receive the study device, and if implantation fails, standard care will be provided. These subjects will not be included in primary or secondary endpoint analyses but will undergo descriptive analysis. Unique numbers will be assigned to all lead-in subjects, and the committee will evaluate outcomes and site independence for future trial recruitment.

Device: Myval THV Series

Interventions

Myval THV Series DEVICE

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.

Also known as: Myval/Myval Inception THVs or any subsequent advanced version commercially available at the study site.

Myval THV Series; Myval THV Series Lead-in Set; Myval THV Series XL Nested Registry

Contemporary Valves (Sapien THV Series and Evolut THV Series) DEVICE

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.

Also known as: 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.

Contemporary Valves

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Meril Life Sciences Pvt. Ltd.: lead

Study Sites (54)

Republican Scientific-Practical Centre "Cardiology"

Minsk, 220036, Belarus

NOT YET RECRUITING

Hospital Dante Pazanesse

São Paulo, 04012-909, Brazil

RECRUITING

Split Clinical Hospital Center

Split, 21000, Croatia

RECRUITING

University Hospital Dubrava Avenija Gojka Šuška 6

Zagreb, 10000, Croatia

RECRUITING

North Estonia Medical Center

Tallinn, Estonia

RECRUITING

Hôpital Henri Mondor

Créteil, 94000, France

RECRUITING

Lille University

Lille, 59000, France

RECRUITING

Institut Cardiovascular Paris-Sud

Massy, 91300, France

RECRUITING

Arnault Tzanck Institute

Nice, 06200, France

RECRUITING

Centre Hospitalier Universitaire De Rennes

Rennes, 35033, France

NOT YET RECRUITING

Kerckhoff-KlinikForschungs GmbH

Bad Nauheim, Hesse, 61231, Germany

RECRUITING

Leipzig Heart Institute GmbH

Leipzig, Saxony, 04289, Germany

RECRUITING

University Herzentrum Division of Cardiology and Angiology II,University Heart Center Freiburg, Südring 15

Bad Krozingen, 79189, Germany

RECRUITING

Klinikum Braunschweig Freisestre

Braunschweig, 38118, Germany

ACTIVE NOT RECRUITING

Technology University Dresden Fetscherstraße 76

Dresden, 01307, Germany

RECRUITING

Asklepios Kliniken Hamburg Gmbh Lohmuehlenstrasse 5

Hamburg, 20099, Germany

NOT YET RECRUITING

Klinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg

Regensburg, 93053, Germany

RECRUITING

Hippkration Hospital

Athens, 11527, Greece

RECRUITING

Hygeia hospital

Marousi, Greece

RECRUITING

Interbalkan European Medical Center

Thessaloniki, 555 35, Greece

RECRUITING

Semmelweis University

Budapest, 1122, Hungary

RECRUITING

University of Bologna Policlinico S. Orsola-Malpigh

Bologna, 40141, Italy

NOT YET RECRUITING

Policlinico di Catania

Catania, 95100, Italy

NOT YET RECRUITING

San Donato Hospital

Milan, 20121-20162, Italy

RECRUITING

San Raffaele Hospital

Milan, 20132, Italy

RECRUITING

Clinical Institute Saint Ambrogio

Milan, 20149, Italy

RECRUITING

Mauriliano Hospital Largo Filippo

Tortona, 10128, Italy

NOT YET RECRUITING

University Hospital Città della Salute e della Scienza Turin Bramante

Turin, 10126, Italy

NOT YET RECRUITING

St Antonius Hospital

Nieuwegein, Dutch, 3435, Netherlands

RECRUITING

Radboud University Nijmegen

Nijmegen, Gelderland, 6525 XZ, Netherlands

RECRUITING

Isala Zwolle Hospital

Zwolle, Overijssel, 8025 AB, Netherlands

ACTIVE NOT RECRUITING

Onze lieve vrouwe gasthuis Oosterperk 9

Amsterdam, 1091, Netherlands

ACTIVE NOT RECRUITING

Amphia Ziekenhui Hospital

Breda, 4817, Netherlands

RECRUITING

University Medical Center (UMC)

Groningen, 9713, Netherlands

NOT YET RECRUITING

University Medical Center Utrecht

Utrecht, 3584, Netherlands

RECRUITING

Auckland City Hospital 2 Park Road

Grafton, Auckland, 1023, New Zealand

RECRUITING

John Paul II Hospital

Krakow, Małopolskie Województwo, 31-202, Poland

NOT YET RECRUITING

University of Gdansk

Gdansk, Pomorskie Województwo, 80-952, Poland

NOT YET RECRUITING

Medical University of Silesia

Katowice, Prussian, 40-635, Poland

NOT YET RECRUITING

Institute of Cardiology

Warsaw, 50-013, Poland

NOT YET RECRUITING

Uniwersytecki Szpital Kliniczny (USK) Curie-Skłodowskiej 58

Wroclaw, 50-369, Poland

RECRUITING

Centro Hospitalar Lisboa Ocidental EPE- Hospital Santa Cruz, Av. Prof. Dr. Reinaldo dos Santos

Carnaxide, 2790-134, Portugal

RECRUITING

Centro Hospital Lisboa Central E.P.E. - Santa Marta

Lisbon, 1169-024, Portugal

RECRUITING

Hospital de Santa Maria, Av. Prof. Egas Moniz MB

Lisbon, 1649-028, Portugal

NOT YET RECRUITING

Centro Hospitalar de Sao Joao

Porto, 4200-319, Portugal

NOT YET RECRUITING

University hospital Banska Bystrica Námestie Ludvíka Svobodu 1

Banská Bystrica, 975 17, Slovakia

RECRUITING

University Medical Center, Ljubljana

Ljubljana, 1000, Slovenia

RECRUITING

Hospital Universitari Son Espases Carretera de Valldemossa

Palma de Mallorca, Balearic Islands, 07120, Spain

RECRUITING

Hospital Universitario de Gran Canaria Dr Negrin

Las Palmas, Canary Islands, 35010, Spain

RECRUITING

Hospital Universitario Renei Sofia

Córdoba, 5000, Spain

RECRUITING

Hospital Clínico San Carlos

Madrid, 28040, Spain

NOT YET RECRUITING

Hospital Cliinico Univertistario de Valladolid

Valladolid, 47003, Spain

RECRUITING

Sahlgrenska University Hospital

Gothenburg, Sweden

RECRUITING

Uppsala University Hospital

Uppsala, Sweden

RECRUITING

Related Publications (6)

• 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.

  PMID: 33160946 BACKGROUND

• Tobe A, Onuma Y, Soliman O, Baumbach A, Serruys PW. LANDMARK trial: Update in study protocol. Am Heart J. 2024 Apr;270:162-163. doi: 10.1016/j.ahj.2024.02.008. Epub 2024 Feb 16. No abstract available.

  PMID: 38369219 BACKGROUND

• Baumbach A, van Royen N, Amat-Santos IJ, Hudec M, Bunc M, Ijsselmuiden A, Laanmets P, Unic D, Merkely B, Hermanides RS, Ninios V, Protasiewicz M, Rensing BJWM, Martin PL, Feres F, De Sousa Almeida M, van Belle E, Linke A, Ielasi A, Montorfano M, Webster M, Toutouzas K, Teiger E, Bedogni F, Voskuil M, Pan M, Angeras O, Kim WK, Rothe J, Kristic I, Peral V, Garg S, Elzomor H, Tobe A, Morice MC, Onuma Y, Soliman O, Serruys PW; LANDMARK trial investigators. LANDMARK comparison of early outcomes of newer-generation Myval transcatheter heart valve series with contemporary valves (Sapien and Evolut) in real-world individuals with severe symptomatic native aortic stenosis: a randomised non-inferiority trial. Lancet. 2024 Jun 22;403(10445):2695-2708. doi: 10.1016/S0140-6736(24)00821-3. Epub 2024 May 22.

  PMID: 38795719 RESULT

• Royen NV, Amat-Santos IJ, Hudec M, Bunc M, Ijsselmuiden A, Laanmets P, Unic D, Merkely B, Hermanides RS, Ninios V, Protasiewicz M, Rensing BJWM, Martin PL, Feres F, Sousa M, Belle EV, Linke A, Ielasi A, Montorfano M, Webster M, Toutouzas K, Teiger E, Bedogni F, Voskuil M, Pan M, Angeras O, Kim WK, Rothe J, Kristic I, Peral V, Van den Branden BJL, Westermann D, Bellini B, Garcia-Gomez M, Tobe A, Tsai TY, Garg S, Thakkar A, Chandra U, Morice MC, Soliman O, Onuma Y, Serruys PW, Baumbach A. Early outcomes of the novel Myval THV series compared to SAPIEN THV series and Evolut THV series in individuals with severe aortic stenosis. EuroIntervention. 2025 Jan 20;21(2):e105-e118. doi: 10.4244/EIJ-D-24-00951.

  PMID: 39589296 RESULT

• Serruys PW, Tobe A, van Royen N, Amat-Santos IJ, Hudec M, Bunc M, Van den Branden BJL, Laanmets P, Unic D, Merkely B, Hermanides RS, Ninios V, Protasiewicz M, Rensing BJWM, Martin PL, Feres F, De Sousa Almeida M, van Belle E, Linke A, Ielasi A, Montorfano M, Webster M, Toutouzas K, Teiger E, Bedogni F, Voskuil M, Pan M, Angeras O, Kim WK, Rothe J, Abdel-Wahab M, Kristic I, Peral V, Garg S, Tsai TY, Thakkar A, Chandra U, Smits PC, Morice MC, Onuma Y, Baumbach A; LANDMARK Investigators. 1-Year Outcomes of Novel Balloon-Expandable vs Contemporary Transcatheter Heart Valves in Severe Aortic Stenosis: The LANDMARK Trial. J Am Coll Cardiol. 2025 Nov 16:S0735-1097(25)10159-9. doi: 10.1016/j.jacc.2025.10.076. Online ahead of print.

  PMID: 41384893 DERIVED

• 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.

  PMID: 33833944 DERIVED

Related Links

• 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
• LANDMARK comparison of early outcomes of newer-generation Myval transcatheter heart valve series with contemporary valves (Sapien and Evolut) in real-world individuals with severe symptomatic native aortic stenosis:a randomised non-inferiority trial.
• Early outcomes of the novel Myval THV series compared to SAPIEN THV series and Evolut THV series in individuals with severe aortic stenosis. EuroIntervention
• LANDMARK trial: Update in study protocol.

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Andreas Baumbach, MD,FESC,FRCP

  Barts Heart Center, London, UK

  STUDY CHAIR

• Patrick W. Serruys, MD,PhD,FACC,FESC

  National University of Ireland, Galway, Ireland

  STUDY DIRECTOR

Central Study Contacts

Ashok Thakkar, PhD

CONTACT

+91-9879443584; ashok.thakkar@merillife.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: February 4, 2020
• First Posted: February 19, 2020
• Study Start: November 4, 2020
• Primary Completion: March 7, 2024
• Study Completion (Estimated): December 31, 2033
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); BR (1); HU (1); GR (3); NZ (1); FR (5); DE (7); PT (4); SL (1); BE (1); PL (5); CR (2); IT (7); SE (2); NL (7)