LANDMARK Trial: a Randomised Controlled Trial of Myval THV

Not Applicable

Recruiting

• Conditions: Aortic Valve Stenosis

• Registration Number: NCT04275726
• Lead Sponsor: Meril Life Sciences Pvt. Ltd.

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.

Study Timeline

• Study First Submitted: 2020-02-04
• Study First Submitted QC: 2020-02-17
• Study First Posted: 2020-02-19
• Study Start: 2020-11-04
• Primary Completion: 2024-03-07
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-04
• Study Completion: 2033-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 988

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)	30-day	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

Secondary Outcome Measures

Name	Time	Method
Major vascular complications	Pre-discharge, 30-day, and 1-year	As per VARC-3 defined criteria
Bleeding (Type 3 and 4)	Pre-discharge, 30-day, 1-year, 3-year, and 5-year	As per VARC-3 defined criteria
Clinical efficacy at 30 days	After 30 days of index procedure	As per VARC-3 defined criteria
The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)	1-year	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
All stroke	Pre-discharge, 30-day, 1-year, 3-year, and 5-year	As per VARC-3 defined criteria
Acute Kidney Injury (AKI) (Stage 2, 3 and 4)	Pre-discharge, 30-day, and 1-year	As per VARC-3 defined criteria
Valve related long-term clinical efficacy	5-years, 7 years and 10 years	As per VARC-3 defined criteria
Vascular and access related complications	Pre-discharge, 30-day, and 1-year	As per VARC-3 defined criteria
Functional improvement from baseline as measured per	[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]	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 \[Time frame: Baseline (pre-procedure), 30-day and 1-year\]
Re-hospitalization	30-day, 1-year, 3-year, and 5-year	As per VARC-3 defined criteria
Valve thrombosis	30-day, 1-year, 3-year, and 5-year	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.
Conversion to open surgery	Pre-discharge	As per VARC-3 defined criteria
Implantation of multiple (>1) transcatheter valves during the index hospitalization	Index-procedure	As per VARC-3 defined criteria
Cardiac structural complications	30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years	As per VARC-3 defined criteria
Myocardial Infarction	Pre-discharge, 30-day, 1-year, 3-year, and 5-year	As per VARC-3 defined criteria
Early safety at 30 days	30-day	As per VARC-3 defined criteria
Coronary obstruction requiring intervention	Pre-discharge	As per VARC-3 defined criteria
All-cause mortality	Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4 year, 5-year, 7-year, and 10-year	As per VARC-3 defined criteria
Moderate or severe prosthetic valve regurgitation	Pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year	As per VARC-3 defined criteria
New permanent pacemaker implantation (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	o New PPI rates will be analysed further based on the patient's history of left and/or right bundle branch block.
Conduction disturbances and arrhythmias	Pre-discharge, 30-day, 1-year, 3-year, and 5-year	As per VARC-3 defined criteria
Echocardiographic endpoints	Baseline, pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year	* 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
Length of index hospital stay	At discharge	o Number of days from hospital admission to discharge.
Health status as evaluated by Quality of Life questionnaires	Baseline (pre-procedure), 30-day, and 1-year	o 12-Item Short Form Survey (SF-12)
Valve malpositioning	Pre-discharge	As per VARC-3 defined criteria
Unplanned use of mechanical circulatory support (cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), transcatheter pumps or intra-aortic balloon pump (IABP)	Pre-discharge	As per VARC-3 defined criteria
Technical success	Post-procedure	As per VARC-3 defined criteria
Endocarditis	30-day, 1-year, 3-year, and 5-year	As per VARC-3 defined criteria
Bioprosthetic valve deterioration	Pre-discharge, 30-day, 1-year, 3-year, and 5-year	As per VARC-3 defined criteria
Patient-prosthesis mismatch	Pre-discharge, 30-day, and 1-year	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
Ventricular septal perforation	Pre-discharge	o Angiographic or echocardiographic evidence of a new septal perforation during or after the TAVI procedure
New onset of atrial fibrillation or atrial flutter	Pre-discharge, 30-day, 1-year, 3-year, and 5-year	As per VARC-3 defined criteria
Device success	Pre-discharge and 30-day	As per VARC-3 defined criteria

Trial Locations

Locations (54)

Republican Scientific-Practical Centre "Cardiology"; 🇧🇾 Minsk, Belarus

Hospital Dante Pazanesse; 🇧🇷 São Paulo, Brazil

Split Clinical Hospital Center; 🇭🇷 Split, Croatia

University Hospital Dubrava Avenija Gojka Šuška 6; 🇭🇷 Zagreb, Croatia

North Estonia Medical Center; 🇪🇪 Tallinn, Estonia

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, France

Scroll for more (44 remaining)