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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-000137-40 | EudraCT Number |
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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)
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Contemporary Valves | Active Comparator |
This treatment arm will be assigned to 384 / 768 subjects enrolled in a study. |
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| 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 |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3) | It is the composite of following:
| 30-day |
| Measure | Description | Time Frame |
|---|---|---|
| The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3) | It is the composite of following:
| 1-year |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ashok Thakkar, PhD | Contact | +91-9879443584 | ashok.thakkar@merillife.com |
| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Republican Scientific-Practical Centre "Cardiology" | Not yet recruiting | Minsk | 220036 | Belarus |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33160946 | Background | 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. | |
| 38369219 |
| Label | URL |
|---|---|
| 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 | View source |
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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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| 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. |
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| All-cause mortality | 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 | 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) | As per VARC-3 defined criteria | Pre-discharge, 30-day, and 1-year |
| Bleeding (Type 3 and 4) | As per VARC-3 defined criteria | Pre-discharge, 30-day, 1-year, 3-year, and 5-year |
| Moderate or severe prosthetic valve regurgitation | 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) | 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 | As per VARC-3 defined criteria | Pre-discharge, 30-day, 1-year, 3-year, and 5-year |
| Device success | As per VARC-3 defined criteria | Pre-discharge and 30-day |
| Early safety at 30 days | As per VARC-3 defined criteria | 30-day |
| Clinical efficacy at 30 days | As per VARC-3 defined criteria | After 30 days of index procedure |
| Valve related long-term clinical efficacy | As per VARC-3 defined criteria | 5-years, 7 years and 10 years |
| Vascular and access related complications | As per VARC-3 defined criteria | Pre-discharge, 30-day, and 1-year |
| Major vascular complications | As per VARC-3 defined criteria | Pre-discharge, 30-day, and 1-year |
| Functional improvement from baseline as measured per | 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 |
| Baseline, pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year |
| Bioprosthetic valve deterioration | As per VARC-3 defined criteria | Pre-discharge, 30-day, 1-year, 3-year, and 5-year |
| Patient-prosthesis mismatch | Severity patient-prosthesis-mismatch will be based on following
| Pre-discharge, 30-day, and 1-year |
| Length of index hospital stay | o Number of days from hospital admission to discharge. | At discharge |
| Re-hospitalization | As per VARC-3 defined criteria | 30-day, 1-year, 3-year, and 5-year |
| Health status as evaluated by Quality of Life questionnaires | o 12-Item Short Form Survey (SF-12) | Baseline (pre-procedure), 30-day, and 1-year |
| Valve thrombosis | 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 | As per VARC-3 defined criteria | Pre-discharge |
| Valve malpositioning | As per VARC-3 defined criteria | Pre-discharge |
| Conversion to open surgery | 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) | As per VARC-3 defined criteria | Pre-discharge |
| Implantation of multiple (>1) transcatheter valves during the index hospitalization | As per VARC-3 defined criteria | Index-procedure |
| Cardiac structural complications | As per VARC-3 defined criteria | 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years |
| Ventricular septal perforation | 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 | As per VARC-3 defined criteria | Pre-discharge, 30-day, 1-year, 3-year, and 5-year |
| Technical success | As per VARC-3 defined criteria | Post-procedure |
| Myocardial Infarction | As per VARC-3 defined criteria | Pre-discharge, 30-day, 1-year, 3-year, and 5-year |
| Endocarditis | As per VARC-3 defined criteria | 30-day, 1-year, 3-year, and 5-year |
| Hospital Dante Pazanesse | Recruiting | São Paulo | 04012-909 | Brazil |
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| Split Clinical Hospital Center | Recruiting | Split | 21000 | Croatia |
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| University Hospital Dubrava Avenija Gojka Šuška 6 | Recruiting | Zagreb | 10000 | Croatia |
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| North Estonia Medical Center | Recruiting | Tallinn | Estonia |
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| Hôpital Henri Mondor | Recruiting | Créteil | 94000 | France |
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| Lille University | Recruiting | Lille | 59000 | France |
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| Institut Cardiovascular Paris-Sud | Recruiting | Massy | 91300 | France |
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| Arnault Tzanck Institute | Recruiting | Nice | 06200 | France |
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| Centre Hospitalier Universitaire De Rennes | Not yet recruiting | Rennes | 35033 | France |
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| Kerckhoff-KlinikForschungs GmbH | Recruiting | Bad Nauheim | Hesse | 61231 | Germany |
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| Leipzig Heart Institute GmbH | Recruiting | Leipzig | Saxony | 04289 | Germany |
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| University Herzentrum Division of Cardiology and Angiology II,University Heart Center Freiburg, Südring 15 | Recruiting | Bad Krozingen | 79189 | Germany |
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| Klinikum Braunschweig Freisestre | Active, not recruiting | Braunschweig | 38118 | Germany |
| Technology University Dresden Fetscherstraße 76 | Recruiting | Dresden | 01307 | Germany |
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| Asklepios Kliniken Hamburg Gmbh Lohmuehlenstrasse 5 | Not yet recruiting | Hamburg | 20099 | Germany |
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| Klinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg | Recruiting | Regensburg | 93053 | Germany |
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| Hippkration Hospital | Recruiting | Athens | 11527 | Greece |
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| Hygeia hospital | Recruiting | Marousi | Greece |
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| Interbalkan European Medical Center | Recruiting | Thessaloniki | 555 35 | Greece |
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| Semmelweis University | Recruiting | Budapest | 1122 | Hungary |
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| University of Bologna Policlinico S. Orsola-Malpigh | Not yet recruiting | Bologna | 40141 | Italy |
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| Policlinico di Catania | Not yet recruiting | Catania | 95100 | Italy |
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| San Donato Hospital | Recruiting | Milan | 20121-20162 | Italy |
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| San Raffaele Hospital | Recruiting | Milan | 20132 | Italy |
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| Clinical Institute Saint Ambrogio | Recruiting | Milan | 20149 | Italy |
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| Mauriliano Hospital Largo Filippo | Not yet recruiting | Tortona | 10128 | Italy |
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| University Hospital Città della Salute e della Scienza Turin Bramante | Not yet recruiting | Turin | 10126 | Italy |
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| St Antonius Hospital | Recruiting | Nieuwegein | Dutch | 3435 | Netherlands |
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| Radboud University Nijmegen | Recruiting | Nijmegen | Gelderland | 6525 XZ | Netherlands |
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| Isala Zwolle Hospital | Active, not recruiting | Zwolle | Overijssel | 8025 AB | Netherlands |
| Onze lieve vrouwe gasthuis Oosterperk 9 | Active, not recruiting | Amsterdam | 1091 | Netherlands |
| Amphia Ziekenhui Hospital | Recruiting | Breda | 4817 | Netherlands |
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| University Medical Center (UMC) | Not yet recruiting | Groningen | 9713 | Netherlands |
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| University Medical Center Utrecht | Recruiting | Utrecht | 3584 | Netherlands |
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| Auckland City Hospital 2 Park Road | Recruiting | Grafton | Auckland | 1023 | New Zealand |
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| John Paul II Hospital | Not yet recruiting | Krakow | Małopolskie Województwo | 31-202 | Poland |
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| University of Gdansk | Not yet recruiting | Gdansk | Pomorskie Województwo | 80-952 | Poland |
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| Medical University of Silesia | Not yet recruiting | Katowice | Prussian | 40-635 | Poland |
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| Institute of Cardiology | Not yet recruiting | Warsaw | 50-013 | Poland |
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| Uniwersytecki Szpital Kliniczny (USK) Curie-Skłodowskiej 58 | Recruiting | Wroclaw | 50-369 | Poland |
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| Centro Hospitalar Lisboa Ocidental EPE- Hospital Santa Cruz, Av. Prof. Dr. Reinaldo dos Santos | Recruiting | Carnaxide | 2790-134 | Portugal |
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| Centro Hospital Lisboa Central E.P.E. - Santa Marta | Recruiting | Lisbon | 1169-024 | Portugal |
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| Hospital de Santa Maria, Av. Prof. Egas Moniz MB | Not yet recruiting | Lisbon | 1649-028 | Portugal |
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| Centro Hospitalar de Sao Joao | Not yet recruiting | Porto | 4200-319 | Portugal |
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| University hospital Banska Bystrica Námestie Ludvíka Svobodu 1 | Recruiting | Banská Bystrica | 975 17 | Slovakia |
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| University Medical Center, Ljubljana | Recruiting | Ljubljana | 1000 | Slovenia |
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| Hospital Universitari Son Espases Carretera de Valldemossa | Recruiting | Palma de Mallorca | Balearic Islands | 07120 | Spain |
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| Hospital Universitario de Gran Canaria Dr Negrin | Recruiting | Las Palmas | Canary Islands | 35010 | Spain |
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| Hospital Universitario Renei Sofia | Recruiting | Córdoba | 5000 | Spain |
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| Hospital Clínico San Carlos | Not yet recruiting | Madrid | 28040 | Spain |
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| Hospital Cliinico Univertistario de Valladolid | Recruiting | Valladolid | 47003 | Spain |
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| Sahlgrenska University Hospital | Recruiting | Gothenburg | Sweden |
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| Uppsala University Hospital | Recruiting | Uppsala | Sweden |
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| 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. |
| 38795719 | Result | 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. |
| 39589296 | 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. |
| 41384893 | Derived | 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. 2026 Feb 3;87(4):362-381. doi: 10.1016/j.jacc.2025.10.076. Epub 2025 Nov 16. |
| 40875489 | Derived | Soliman O, Hasabo EA, van Royen N, Amat-Santos IJ, Hudec M, Bunc M, IJsselmuiden A, Laanmets P, Unic D, Merkely B, Hermanides RS, Mouden M, Ninios V, Protasiewicz M, Rensing BJWM, Martin PL, Feres F, Almeida MS, van Belle E, Linke A, Ielasi A, Montorfano M, Webster M, Toutouzas K, Teiger E, Bedogni F, Voskuil M, Rubio DM, Angeras O, Kim WK, Rothe J, Kristic I, Peral V, Van den Branden BJL, Thakkar A, Chandra U, Neiroukh D, Ayhan C, Nosir MY, Yacoub MS, Ali S, Altamimi M, Elzomor H, Serruys PW, Baumbach A. Comparative 30-day echocardiographic outcomes of Myval vs. Sapien and Evolut THVs: insights from LANDMARK trial. Eur Heart J Cardiovasc Imaging. 2026 Feb 9;27(2):247-260. doi: 10.1093/ehjci/jeaf245. |
| 33833944 | 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. |
| 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. | View source |
| Early outcomes of the novel Myval THV series compared to SAPIEN THV series and Evolut THV series in individuals with severe aortic stenosis. EuroIntervention | View source |
| LANDMARK trial: Update in study protocol. | View source |
| ID | Term |
|---|---|
| D001024 | Aortic Valve Stenosis |
| ID | Term |
|---|---|
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014694 | Ventricular Outflow Obstruction |
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