LANDMARK Trial: a Randomised Controlled Trial of Myval THV

NCT ID: NCT04275726

Last Updated: 2025-04-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

988 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-04

Study Completion Date

2033-12-31

Brief Summary

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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

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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.

Conditions

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Aortic Valve Stenosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Myval THV Series

Intervention Type 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.

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.

Group Type ACTIVE_COMPARATOR

Contemporary Valves (Sapien THV Series and Evolut THV Series)

Intervention Type 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.

Myval THV Series XL Nested Registry

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

Group Type EXPERIMENTAL

Myval THV Series

Intervention Type 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.

Myval THV Series Lead-in Set

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.

Group Type EXPERIMENTAL

Myval THV Series

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DEVICE

Other Intervention Names

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

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Meril Life Sciences Pvt. Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andreas Baumbach, MD,FESC,FRCP

Role: STUDY_CHAIR

Barts Heart Center, London, UK

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

Role: STUDY_DIRECTOR

National University of Ireland, Galway, Ireland

Locations

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Republican Scientific-Practical Centre "Cardiology"

Minsk, , Belarus

Site Status NOT_YET_RECRUITING

Hospital Dante Pazanesse

São Paulo, , Brazil

Site Status RECRUITING

Split Clinical Hospital Center

Split, , Croatia

Site Status RECRUITING

University Hospital Dubrava Avenija Gojka Šuška 6

Zagreb, , Croatia

Site Status RECRUITING

North Estonia Medical Center

Tallinn, , Estonia

Site Status RECRUITING

Hôpital Henri Mondor

Créteil, , France

Site Status RECRUITING

Lille University

Lille, , France

Site Status RECRUITING

Institut Cardiovascular Paris-Sud

Massy, , France

Site Status RECRUITING

Arnault Tzanck Institute

Nice, , France

Site Status RECRUITING

Centre Hospitalier Universitaire De Rennes

Rennes, , France

Site Status NOT_YET_RECRUITING

Kerckhoff-KlinikForschungs GmbH

Bad Nauheim, Hesse, Germany

Site Status RECRUITING

Leipzig Heart Institute GmbH

Leipzig, Saxony, Germany

Site Status RECRUITING

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

Bad Krozingen, , Germany

Site Status RECRUITING

Klinikum Braunschweig Freisestre

Braunschweig, , Germany

Site Status ACTIVE_NOT_RECRUITING

Technology University Dresden Fetscherstraße 76

Dresden, , Germany

Site Status RECRUITING

Asklepios Kliniken Hamburg Gmbh Lohmuehlenstrasse 5

Hamburg, , Germany

Site Status NOT_YET_RECRUITING

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

Regensburg, , Germany

Site Status RECRUITING

Hippkration Hospital

Athens, , Greece

Site Status RECRUITING

Hygeia hospital

Marousi, , Greece

Site Status RECRUITING

Interbalkan European Medical Center

Thessaloniki, , Greece

Site Status RECRUITING

Semmelweis University

Budapest, , Hungary

Site Status RECRUITING

University of Bologna Policlinico S. Orsola-Malpigh

Bologna, , Italy

Site Status NOT_YET_RECRUITING

Policlinico di Catania

Catania, , Italy

Site Status NOT_YET_RECRUITING

San Donato Hospital

Milan, , Italy

Site Status RECRUITING

San Raffaele Hospital

Milan, , Italy

Site Status RECRUITING

Clinical Institute Saint Ambrogio

Milan, , Italy

Site Status RECRUITING

Mauriliano Hospital Largo Filippo

Tortona, , Italy

Site Status NOT_YET_RECRUITING

University Hospital Città della Salute e della Scienza Turin Bramante

Turin, , Italy

Site Status NOT_YET_RECRUITING

St Antonius Hospital

Nieuwegein, Dutch, Netherlands

Site Status RECRUITING

Radboud University Nijmegen

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Isala Zwolle Hospital

Zwolle, Overijssel, Netherlands

Site Status ACTIVE_NOT_RECRUITING

Onze lieve vrouwe gasthuis Oosterperk 9

Amsterdam, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Amphia Ziekenhui Hospital

Breda, , Netherlands

Site Status RECRUITING

University Medical Center (UMC)

Groningen, , Netherlands

Site Status NOT_YET_RECRUITING

University Medical Center Utrecht

Utrecht, , Netherlands

Site Status RECRUITING

Auckland City Hospital 2 Park Road

Grafton, Auckland, New Zealand

Site Status RECRUITING

John Paul II Hospital

Krakow, Małopolskie Województwo, Poland

Site Status NOT_YET_RECRUITING

University of Gdansk

Gdansk, Pomorskie Województwo, Poland

Site Status NOT_YET_RECRUITING

Medical University of Silesia

Katowice, Prussian, Poland

Site Status NOT_YET_RECRUITING

Institute of Cardiology

Warsaw, , Poland

Site Status NOT_YET_RECRUITING

Uniwersytecki Szpital Kliniczny (USK) Curie-Skłodowskiej 58

Wroclaw, , Poland

Site Status RECRUITING

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

Carnaxide, , Portugal

Site Status RECRUITING

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

Lisbon, , Portugal

Site Status RECRUITING

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

Lisbon, , Portugal

Site Status NOT_YET_RECRUITING

Centro Hospitalar de Sao Joao

Porto, , Portugal

Site Status NOT_YET_RECRUITING

University hospital Banska Bystrica Námestie Ludvíka Svobodu 1

Banská Bystrica, , Slovakia

Site Status RECRUITING

University Medical Center, Ljubljana

Ljubljana, , Slovenia

Site Status RECRUITING

Hospital Universitari Son Espases Carretera de Valldemossa

Palma de Mallorca, Balearic Islands, Spain

Site Status RECRUITING

Hospital Universitario de Gran Canaria Dr Negrin

Las Palmas, Canary Islands, Spain

Site Status RECRUITING

Hospital Universitario Renei Sofia

Córdoba, , Spain

Site Status RECRUITING

Hospital Clínico San Carlos

Madrid, , Spain

Site Status NOT_YET_RECRUITING

Hospital Cliinico Univertistario de Valladolid

Valladolid, , Spain

Site Status RECRUITING

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status RECRUITING

Uppsala University Hospital

Uppsala, , Sweden

Site Status RECRUITING

Countries

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Belarus Brazil Croatia Estonia France Germany Greece Hungary Italy Netherlands New Zealand Poland Portugal Slovakia Slovenia Spain Sweden

Central Contacts

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Ashok Thakkar, PhD

Role: CONTACT

+91-9879443584

Facility Contacts

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Dr. Oleg Polonetsky, MD, PhD

Role: primary

Dr. Fausto Feres

Role: primary

Dr. Ivica Kristic, MD, PhD

Role: primary

Dr. Daniel Unić, MD

Role: primary

+385989196621

Dr. Peep Laanmets

Role: primary

Prof. Emmanuel Teiger

Role: primary

Prof. Eric Van Belle

Role: primary

Dr. Bernard Chevalier

Role: primary

Dr. ADJEDJ Julien

Role: primary

Dr. Vincent Auffret

Role: primary

Dr. Won K Kim, M.D

Role: primary

+49 60326152

Prof Mohamed A Wahab, Ph. D

Role: primary

+493418650

Dr. Jurgen Rothe

Role: primary

Prof. Dr. Axel Linke

Role: primary

Dr. Samer Hakmi, MD

Role: primary

Dr. med. Andreas Holzamer

Role: primary

Prof. Konstantinos Toutouzas

Role: primary

+30 2132088026

Dr. Konstantinos Spargias

Role: primary

Dr. Vlasis Ninios

Role: primary

+302310400929

Prof. Bela Merkely, MD Ph. D

Role: primary

36206632488

Dr. Francesco Saia

Role: primary

Dr. Corrado Tamburino

Role: primary

Dr. Francesco Bedogni

Role: primary

+ 39 335 5309117

Dr. Matteo Montorfano

Role: primary

+39 02 26437331

Dr. Alfonso Ielasi

Role: primary

+39 338 8433189

Prof. Dr. Giuseppe Musumeci

Role: primary

Prof Gaetano Maria De Ferrari

Role: primary

011 6334634

Dr. B.J.W.M Rensing, Cardiologist

Role: primary

+31 306093974

Prof. Niels V Royen, Ph.D

Role: primary

Dr. Van Den Branden, PhD

Role: primary

+31613000745

Dr. Joanna J Wykrzykowska

Role: primary

Dr. Michiel Voskuil

Role: primary

Dr. Mark Webster, MD

Role: primary

+64 9 307 4949

Dr n. med Jaroslaw Trebacz, MD PhD

Role: primary

Prof. Darius Jageilak, MD PhD

Role: primary

+48585844200

Dr. Wojciech Wojakowski, MD PhD

Role: primary

Prof. Adam Witkowski, MD, PhD, FESC

Role: primary

+48 22 812 41 64

Dr. Marcin Protasiewicz

Role: primary

+48 71 7364200

Dr. Manuel Almeida

Role: primary

+351 936359285

Dr. Duarte Cacela

Role: primary

Dr. Pedro Carrilho Ferreira

Role: primary

+351 966 412 473

Dr. Joao Carlos Silva, PhD

Role: primary

Dr. Martin Hudec

Role: primary

+421 918 106033

Prof. Matjaz Bunc, MD, PhD

Role: primary

+38615225050

Dr. Vicente Peral

Role: primary

+34 871205381

Dr. Pedro Martin Lorenzo

Role: primary

+34928450000

Dr. Manuel Pan

Role: primary

Dr. Luis Nombela, MD, PhD

Role: primary

+34629510139

Dr. Ignacio A Santos, Medicine & Surgery

Role: primary

+34657923040

Dr. Oskar Angreas

Role: primary

Prof. Stefan James

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 33160946 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38369219 (View on PubMed)

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.

Reference Type RESULT
PMID: 38795719 (View on PubMed)

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.

Reference Type RESULT
PMID: 39589296 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33833944 (View on PubMed)

Related Links

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https://pubmed.ncbi.nlm.nih.gov/33160946/

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

https://pubmed.ncbi.nlm.nih.gov/38795719/

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.

https://pubmed.ncbi.nlm.nih.gov/39589296/

Early outcomes of the novel Myval THV series compared to SAPIEN THV series and Evolut THV series in individuals with severe aortic stenosis. EuroIntervention

https://pubmed.ncbi.nlm.nih.gov/38369219/

LANDMARK trial: Update in study protocol.

Other Identifiers

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2020-000137-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MLS/MYV-2/LANDMARK

Identifier Type: -

Identifier Source: org_study_id

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