LANDMARK Trial: a Randomised Controlled Trial of Myval THV

Aortic Valve Stenosis Clinical Trial

— LANDMARK  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04275726
• Other study ID #: MLS/MYV-2/LANDMARK
• Secondary ID: 2020-000137-40
• Status: Recruiting
• Phase: N/A
• Start date: November 4, 2020
• Est. completion date: December 31, 2033

Study information

• Verified date: May 2024
• Source: Meril Life Sciences Pvt. Ltd.
• Contact: Ashok Thakkar, PhD
• Phone: +91-9879443584
• Email: ashok.thakkar[@]merillife.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 768
• Est. completion date: December 31, 2033
• Est. primary completion date: March 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic

Intervention

Device:
• 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.
• 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.

Locations

Country	Name	City	State
Belarus	Republican Scientific-Practical Centre "Cardiology"	Minsk
Brazil	Hospital Dante Pazanesse	São Paulo
Croatia	Split Clinical Hospital Center	Split
Croatia	University Hospital Dubrava Avenija Gojka Šuška 6	Zagreb
Estonia	North Estonia Medical Center	Tallinn
France	Hôpital Henri Mondor	Créteil
France	Lille University	Lille
France	Institut Cardiovascular Paris-Sud	Massy
France	Arnault Tzanck Institute	Nice
France	Centre Hospitalier Universitaire De Rennes	Rennes
Germany	University Herzentrum Division of Cardiology and Angiology II,University Heart Center Freiburg, Südring 15	Bad Krozingen
Germany	Kerckhoff-KlinikForschungs GmbH	Bad Nauheim	Hesse
Germany	Klinikum Braunschweig Freisestre	Braunschweig
Germany	Technology University Dresden Fetscherstraße 76	Dresden
Germany	Asklepios Kliniken Hamburg Gmbh Lohmuehlenstrasse 5	Hamburg
Germany	Leipzig Heart Institute GmbH	Leipzig	Saxony
Germany	Klinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg	Regensburg
Greece	Hippkration Hospital	Athens
Greece	Hygeia hospital	Maroúsi
Greece	Interbalkan European Medical Center	Thessaloniki
Hungary	Semmelweis University	Budapest
Italy	University of Bologna Policlinico S. Orsola-Malpigh	Bologna
Italy	Policlinico di Catania	Catania
Italy	San Donato Hospital	Milan
Italy	Clinical Institute Saint Ambrogio	Milano
Italy	San Raffaele Hospital	Milano
Italy	Mauriliano Hospital Largo Filippo	Tortona
Italy	University Hospital Città della Salute e della Scienza Turin Bramante	Turin
Netherlands	Onze lieve vrouwe gasthuis Oosterperk 9	Amsterdam
Netherlands	Amphia Ziekenhui Hospital	Breda
Netherlands	University Medical Center (UMC)	Groningen
Netherlands	St Antonius Hospital	Nieuwegein	Dutch
Netherlands	Radboud University Nijmegen	Nijmegen	Gelderland
Netherlands	University Medical Center Utrecht	Utrecht
Netherlands	Isala Zwolle Hospital	Zwolle	Overijssel
New Zealand	Auckland City Hospital 2 Park Road	Grafton	Auckland
Poland	University of Gdansk	Gdansk	Pomorskie Województwo
Poland	Medical University of Silesia	Katowice	Prussian
Poland	John Paul II Hospital	Krakow	Malopolskie Województwo
Poland	Institute of Cardiology	Warsaw
Poland	Uniwersytecki Szpital Kliniczny (USK) Curie-Sklodowskiej 58	Wroclaw
Portugal	Centro Hospitalar Lisboa Ocidental EPE- Hospital Santa Cruz, Av. Prof. Dr. Reinaldo dos Santos	Carnaxide
Portugal	Hospital de Santa Maria, Av. Prof. Egas Moniz MB	Lisboa
Portugal	Centro Hospital Lisboa Central E.P.E. - Santa Marta	Lisbon
Portugal	Centro Hospitalar de Sao Joao	Porto
Slovakia	University hospital Banska Bystrica Námestie Ludvíka Svobodu 1	Banská Bystrica
Slovenia	University Medical Center, Ljubljana	Ljubljana
Spain	Hospital Universitario Renei Sofia	Córdoba
Spain	Hospital Universitario de Gran Canaria Dr Negrin	Las Palmas	Canary Islands
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitari Son Espases Carretera de Valldemossa	Palma De Mallorca	Illes Balears
Spain	Hospital Cliinico Univertistario de Valladolid	Valladolid
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Uppsala University Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Meril Life Sciences Pvt. Ltd.

Countries where clinical trial is conducted

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

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The 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); AKI (Stage 2, 3 and 4); Major vascular complications; Moderate or severe prosthetic valve regurgitation; Conduction system disturbances resulting in a new PPI	1-year
Secondary	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
Secondary	All stroke	As per VARC-3 defined criteria	Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Secondary	Acute Kidney Injury (AKI) (Stage 2, 3 and 4)	As per VARC-3 defined criteria	Pre-discharge, 30-day, and 1-year
Secondary	Bleeding (Type 3 and 4)	As per VARC-3 defined criteria	Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Secondary	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
Secondary	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
Secondary	Conduction disturbances and arrhythmias	As per VARC-3 defined criteria	Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Secondary	Device success	As per VARC-3 defined criteria	Pre-discharge and 30-day
Secondary	Early safety at 30 days	As per VARC-3 defined criteria	30-day
Secondary	Clinical efficacy at 30 days	As per VARC-3 defined criteria	After 30 days of index procedure
Secondary	Valve related long-term clinical efficacy	As per VARC-3 defined criteria	5-years, 7 years and 10 years
Secondary	Vascular and access related complications	As per VARC-3 defined criteria	Pre-discharge, 30-day, and 1-year
Secondary	Major vascular complications	As per VARC-3 defined criteria	Pre-discharge, 30-day, and 1-year
Secondary	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]
Secondary	Echocardiographic endpoints	Effective orifice area (EOA); Index effective orifice area (iEOA); Mean aortic valve gradient; Peak aortic valve gradient; Peak aortic velocity; Total aortic regurgitation, transvalvular regurgitation (except baseline) and paravalvular regurgitation (except baseline); Left ventricular ejection fraction (LVEF); Valve calcification; Cardiac output and cardiac index	Baseline, pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year
Secondary	Bioprosthetic valve deterioration	As per VARC-3 defined criteria	Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Secondary	Patient-prosthesis mismatch	Severity patient-prosthesis-mismatch will be based on following; For subjects with body mass index (BMI) <30 kg/m2, EOAi: 0.85 - 0.66 cm2 /m2 considered as moderate and =0.65 cm2 /m2 considered as severe; For subjects with BMI =30 kg/m2, EOAi: 0.70 - 0.56 cm2 /m2 considered as moderate and =0.55 cm2 /m2 considered as severe; BMI = weight(kg)/(height (m))2	Pre-discharge, 30-day, and 1-year
Secondary	Length of index hospital stay	o Number of days from hospital admission to discharge.	At discharge
Secondary	Re-hospitalization	As per VARC-3 defined criteria	30-day, 1-year, 3-year, and 5-year
Secondary	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
Secondary	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
Secondary	Coronary obstruction requiring intervention	As per VARC-3 defined criteria	Pre-discharge
Secondary	Valve malpositioning	As per VARC-3 defined criteria	Pre-discharge
Secondary	Conversion to open surgery	As per VARC-3 defined criteria	Pre-discharge
Secondary	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
Secondary	Implantation of multiple (>1) transcatheter valves during the index hospitalization	As per VARC-3 defined criteria	Index-procedure
Secondary	Cardiac structural complications	As per VARC-3 defined criteria	30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	Ventricular septal perforation	o Angiographic or echocardiographic evidence of a new septal perforation during or after the TAVI procedure	Pre-discharge
Secondary	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
Secondary	Technical success	As per VARC-3 defined criteria	Post-procedure
Secondary	Myocardial Infarction	As per VARC-3 defined criteria	Pre-discharge, 30-day, 1-year, 3-year, and 5-year
Secondary	Endocarditis	As per VARC-3 defined criteria	30-day, 1-year, 3-year, and 5-year

External 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