Clinical trial NCT04275726: LANDMARK Trial: a Randomised Controlled Trial of Myval THV
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aortic Valve Stenosis
Keywords: LANDMARK Trial
Trial to evaluate safety & effectiveness of Myval THV
CE Approved Myval THV Series
Lead sponsor: Meril Life Sciences Pvt. Ltd.
Sponsor class: INDUSTRY
First posted: 2020-02-19
Enrollment: 988
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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)

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
timeFrame: 30-day
Secondary outcomes:
measure: The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
timeFrame: 1-year
measure: All-cause mortality
timeFrame: Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4 year, 5-year, 7-year, and 10-year
measure: All stroke
timeFrame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
measure: Acute Kidney Injury (AKI) (Stage 2, 3 and 4)
timeFrame: Pre-discharge, 30-day, and 1-year
measure: Bleeding (Type 3 and 4)
timeFrame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
measure: Moderate or severe prosthetic valve regurgitation
timeFrame: Pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year
measure: New permanent pacemaker implantation (As per VARC-3 defined criteria)
timeFrame: Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4-year, 5-year, 7-year, and 10-year
measure: Conduction disturbances and arrhythmias
timeFrame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
measure: Device success
timeFrame: Pre-discharge and 30-day
measure: Early safety at 30 days
timeFrame: 30-day
measure: Clinical efficacy at 30 days
timeFrame: After 30 days of index procedure
measure: Valve related long-term clinical efficacy
timeFrame: 5-years, 7 years and 10 years
measure: Vascular and access related complications
timeFrame: Pre-discharge, 30-day, and 1-year
measure: Major vascular complications
timeFrame: Pre-discharge, 30-day, and 1-year
measure: Functional improvement from baseline as measured per
timeFrame: [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]
measure: Echocardiographic endpoints
timeFrame: Baseline, pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year
measure: Bioprosthetic valve deterioration
timeFrame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
measure: Patient-prosthesis mismatch
timeFrame: Pre-discharge, 30-day, and 1-year
measure: Length of index hospital stay
timeFrame: At discharge
measure: Re-hospitalization
timeFrame: 30-day, 1-year, 3-year, and 5-year
measure: Health status as evaluated by Quality of Life questionnaires
timeFrame: Baseline (pre-procedure), 30-day, and 1-year
measure: Valve thrombosis
timeFrame: 30-day, 1-year, 3-year, and 5-year
measure: Coronary obstruction requiring intervention
timeFrame: Pre-discharge
measure: Valve malpositioning
timeFrame: Pre-discharge
measure: Conversion to open surgery
timeFrame: Pre-discharge
measure: Unplanned use of mechanical circulatory support (cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), transcatheter pumps or intra-aortic balloon pump (IABP)
timeFrame: Pre-discharge
measure: Implantation of multiple (>1) transcatheter valves during the index hospitalization
timeFrame: Index-procedure
measure: Cardiac structural complications
timeFrame: 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Ventricular septal perforation
timeFrame: Pre-discharge
measure: New onset of atrial fibrillation or atrial flutter
timeFrame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
measure: Technical success
timeFrame: Post-procedure
measure: Myocardial Infarction
timeFrame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year
measure: Endocarditis
timeFrame: 30-day, 1-year, 3-year, and 5-year
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: Republican Scientific-Practical Centre "Cardiology"
city: São Paulo
country: Brazil
facility: Hospital Dante Pazanesse
city: Split
country: Croatia
facility: Split Clinical Hospital Center
city: Zagreb
country: Croatia
facility: University Hospital Dubrava Avenija Gojka Šuška 6
city: Tallinn
country: Estonia
facility: North Estonia Medical Center
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Lille
country: France
facility: Lille University
city: Massy
country: France
facility: Institut Cardiovascular Paris-Sud
city: Nice
country: France
facility: Arnault Tzanck Institute
city: Rennes
country: France
facility: Centre Hospitalier Universitaire De Rennes
city: Bad Nauheim
country: Germany
facility: Kerckhoff-KlinikForschungs GmbH
state: Hesse
city: Leipzig
country: Germany
facility: Leipzig Heart Institute GmbH
state: Saxony
city: Bad Krozingen
country: Germany
facility: University Herzentrum Division of Cardiology and Angiology II,University Heart Center Freiburg, Südring 15
city: Braunschweig
country: Germany
facility: Klinikum Braunschweig Freisestre
city: Dresden
country: Germany
facility: Technology University Dresden Fetscherstraße 76
city: Hamburg
country: Germany
facility: Asklepios Kliniken Hamburg Gmbh Lohmuehlenstrasse 5
city: Regensburg
country: Germany
facility: Klinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg
city: Athens
country: Greece
facility: Hippkration Hospital
city: Maroúsi
country: Greece
facility: Hygeia hospital
city: Thessaloniki
country: Greece
facility: Interbalkan European Medical Center
city: Budapest
country: Hungary
facility: Semmelweis University
city: Bologna
country: Italy
facility: University of Bologna Policlinico S. Orsola-Malpigh
city: Catania
country: Italy
facility: Policlinico di Catania
city: Milano
country: Italy
facility: San Raffaele Hospital
city: Milano
country: Italy
facility: Clinical Institute Saint Ambrogio
city: Milan
country: Italy
facility: San Donato Hospital
city: Tortona
country: Italy
facility: Mauriliano Hospital Largo Filippo
city: Turin
country: Italy
facility: University Hospital Città della Salute e della Scienza Turin Bramante
city: Nieuwegein
country: Netherlands
facility: St Antonius Hospital
state: Dutch
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen
state: Gelderland
city: Zwolle
country: Netherlands
facility: Isala Zwolle Hospital
state: Overijssel
city: Amsterdam
country: Netherlands
facility: Onze lieve vrouwe gasthuis Oosterperk 9
city: Breda
country: Netherlands
facility: Amphia Ziekenhui Hospital
city: Groningen
country: Netherlands
facility: University Medical Center (UMC)
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Grafton
country: New Zealand
facility: Auckland City Hospital 2 Park Road
state: Auckland
city: Krakow
country: Poland
facility: John Paul II Hospital
state: Małopolskie Województwo
city: Gdańsk
country: Poland
facility: University of Gdansk
state: Pomorskie Województwo
city: Katowice
country: Poland
facility: Medical University of Silesia
state: Prussian
city: Warsaw
country: Poland
facility: Institute of Cardiology
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny (USK) Curie-Skłodowskiej 58
city: Carnaxide
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental EPE- Hospital Santa Cruz, Av. Prof. Dr. Reinaldo dos Santos
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria, Av. Prof. Egas Moniz MB
city: Lisbon
country: Portugal
facility: Centro Hospital Lisboa Central E.P.E. - Santa Marta
city: Porto
country: Portugal
facility: Centro Hospitalar de Sao Joao
city: Banská Bystrica
country: Slovakia
facility: University hospital Banska Bystrica Námestie Ludvíka Svobodu 1
city: Ljubljana
country: Slovenia
facility: University Medical Center, Ljubljana
city: Las Palmas
country: Spain
facility: Hospital Universitario de Gran Canaria Dr Negrin
state: Canary Islands
city: Palma De Mallorca
country: Spain
facility: Hospital Universitari Son Espases Carretera de Valldemossa
state: Illes Balears
city: Córdoba
country: Spain
facility: Hospital Universitario Renei Sofia
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Valladolid
country: Spain
facility: Hospital Cliinico Univertistario de Valladolid
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: Barts Heart Center, London, UK
name: Andreas Baumbach, MD,FESC,FRCP
role: STUDY_CHAIR
affiliation: National University of Ireland, Galway, Ireland
name: Patrick W. Serruys, MD,PhD,FACC,FESC
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.