LANDMARK Trial: a Randomised Controlled Trial of Myval THV

Официальное название

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

Обзор

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)

Подробное описание

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.

Вмешательства

• Устройство 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.
• Устройство 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.

Первичные конечные точки

• Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3) [Срок оценки: 30-day]

Вторичные конечные точки (12)

• The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3) [Срок оценки: 1-year]
• All-cause mortality [Срок оценки: Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4 year, 5-year, 7-year, and 10-year]
• All stroke [Срок оценки: Pre-discharge, 30-day, 1-year, 3-year, and 5-year]
• Acute Kidney Injury (AKI) (Stage 2, 3 and 4) [Срок оценки: Pre-discharge, 30-day, and 1-year]
• Bleeding (Type 3 and 4) [Срок оценки: Pre-discharge, 30-day, 1-year, 3-year, and 5-year]
• Moderate or severe prosthetic valve regurgitation [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: Pre-discharge, 30-day, 1-year, 3-year, and 5-year]
• Device success [Срок оценки: Pre-discharge and 30-day]
• Early safety at 30 days [Срок оценки: 30-day]
• Clinical efficacy at 30 days [Срок оценки: After 30 days of index procedure]
• Valve related long-term clinical efficacy [Срок оценки: 5-years, 7 years and 10 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 7 центров

• Kerckhoff-KlinikForschungs GmbH — Bad Nauheim
• Leipzig Heart Institute GmbH — Leipzig
• University Herzentrum Division of Cardiology and Angiology II,University Heart Center Frei — Bad Krozingen
• Klinikum Braunschweig Freisestre — Braunschweig
• Technology University Dresden Fetscherstraße 76 — Dresden
• Asklepios Kliniken Hamburg Gmbh Lohmuehlenstrasse 5 — Hamburg
• Klinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg — Regensburg

Италия · 7 центров

• University of Bologna Policlinico S. Orsola-Malpigh — Bologna
• Policlinico di Catania — Catania
• San Donato Hospital — Milan
• San Raffaele Hospital — Milan
• Clinical Institute Saint Ambrogio — Milan
• Mauriliano Hospital Largo Filippo — Tortona
• University Hospital Città della Salute e della Scienza Turin Bramante — Turin

Нидерланды · 7 центров

• St Antonius Hospital — Nieuwegein
• Radboud University Nijmegen — Nijmegen
• Isala Zwolle Hospital — Zwolle
• Onze lieve vrouwe gasthuis Oosterperk 9 — Amsterdam
• Amphia Ziekenhui Hospital — Breda
• University Medical Center (UMC) — Groningen
• University Medical Center Utrecht — Utrecht

Франция · 5 центров

• Hôpital Henri Mondor — Créteil
• Lille University — Lille
• Institut Cardiovascular Paris-Sud — Massy
• Arnault Tzanck Institute — Nice
• Centre Hospitalier Universitaire De Rennes — Rennes

Польша · 5 центров

• John Paul II Hospital — Krakow
• University of Gdansk — Gdansk
• Medical University of Silesia — Katowice
• Institute of Cardiology — Warsaw
• Uniwersytecki Szpital Kliniczny (USK) Curie-Skłodowskiej 58 — Wroclaw

Испания · 5 центров

• Hospital Universitari Son Espases Carretera de Valldemossa — Palma de Mallorca
• Hospital Universitario de Gran Canaria Dr Negrin — Las Palmas
• Hospital Universitario Renei Sofia — Córdoba
• Hospital Clínico San Carlos — Madrid
• Hospital Cliinico Univertistario de Valladolid — Valladolid

Португалия · 4 центра

• Centro Hospitalar Lisboa Ocidental EPE- Hospital Santa Cruz, Av. Prof. Dr. Reinaldo dos Sa — Carnaxide
• Centro Hospital Lisboa Central E.P.E. - Santa Marta — Lisbon
• Hospital de Santa Maria, Av. Prof. Egas Moniz MB — Lisbon
• Centro Hospitalar de Sao Joao — Porto

Греция · 3 центра

• Hippkration Hospital — Athens
• Hygeia hospital — Marousi
• Interbalkan European Medical Center — Thessaloniki

Хорватия · 2 центра

• Split Clinical Hospital Center — Split
• University Hospital Dubrava Avenija Gojka Šuška 6 — Zagreb

Швеция · 2 центра

• Sahlgrenska University Hospital — Gothenburg
• Uppsala University Hospital — Uppsala

Беларусь · 1 центр

• Republican Scientific-Practical Centre "Cardiology" — Minsk

Бразилия · 1 центр

• Hospital Dante Pazanesse — São Paulo

Эстония · 1 центр

• North Estonia Medical Center — Tallinn

Венгрия · 1 центр

• Semmelweis University — Budapest

Новая Зеландия · 1 центр

• Auckland City Hospital 2 Park Road — Grafton

Словакия · 1 центр

• University hospital Banska Bystrica Námestie Ludvíka Svobodu 1 — Banská Bystrica

Словения · 1 центр

• University Medical Center, Ljubljana — Ljubljana

Публикации

• 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 wi PMID 33160946
• 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
• 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 PMID 38795719
• 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, Ts PMID 39589296
• 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 PMID 41384893
• 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 PMID 40875489
• 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

Идентификаторы

NCT: NCT04275726 · MLS/MYV-2/LANDMARK · 2020-000137-40

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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