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NCT Number: NCT04275726

LANDMARK Trial: a Randomised Controlled Trial of Myval THV

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)

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Key information

Conditions

Aortic Valve Stenosis Aortic Valve Disease Cardiovascular Diseases Heart Diseases Heart Valve Diseases Ventricular Outflow Obstruction

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Republican Scientific-Practical Centre "Cardiology", Minsk, Belarus

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

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.

Other names: Myval/Myval Inception THVs or any subsequent advanced version commercially available at the study site.

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.

Other names: Sapien THV Series (Sapien 3/Sapien 3 Ultra THVs) and Evolut THV Series (Evolut R/Evolut PRO THVs ) or any subsequent advanced version commercially available at the study site.

Primary outcomes

  1. Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)

    Time frame: 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 outcomes

  1. The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)

    Time frame: 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

  2. All-cause mortality

    Time frame: 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

  3. All stroke

    Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year

    As per VARC-3 defined criteria

  4. Acute Kidney Injury (AKI) (Stage 2, 3 and 4)

    Time frame: Pre-discharge, 30-day, and 1-year

    As per VARC-3 defined criteria

  5. Bleeding (Type 3 and 4)

    Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year

    As per VARC-3 defined criteria

  6. Moderate or severe prosthetic valve regurgitation

    Time frame: Pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year

    As per VARC-3 defined criteria

  7. New permanent pacemaker implantation (As per VARC-3 defined criteria)

    Time frame: 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.

  8. Conduction disturbances and arrhythmias

    Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year

    As per VARC-3 defined criteria

  9. Device success

    Time frame: Pre-discharge and 30-day

    As per VARC-3 defined criteria

  10. Early safety at 30 days

    Time frame: 30-day

    As per VARC-3 defined criteria

  11. Clinical efficacy at 30 days

    Time frame: After 30 days of index procedure

    As per VARC-3 defined criteria

  12. Valve related long-term clinical efficacy

    Time frame: 5-years, 7 years and 10 years

    As per VARC-3 defined criteria

  13. Vascular and access related complications

    Time frame: Pre-discharge, 30-day, and 1-year

    As per VARC-3 defined criteria

  14. Major vascular complications

    Time frame: Pre-discharge, 30-day, and 1-year

    As per VARC-3 defined criteria

  15. Functional improvement from baseline as measured per

    Time frame: [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]

  16. Echocardiographic endpoints

    Time frame: 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

  17. Bioprosthetic valve deterioration

    Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year

    As per VARC-3 defined criteria

  18. Patient-prosthesis mismatch

    Time frame: 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

  19. Length of index hospital stay

    Time frame: At discharge

    o Number of days from hospital admission to discharge.

  20. Re-hospitalization

    Time frame: 30-day, 1-year, 3-year, and 5-year

    As per VARC-3 defined criteria

  21. Health status as evaluated by Quality of Life questionnaires

    Time frame: Baseline (pre-procedure), 30-day, and 1-year

    o 12-Item Short Form Survey (SF-12)

  22. Valve thrombosis

    Time frame: 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.

  23. Coronary obstruction requiring intervention

    Time frame: Pre-discharge

    As per VARC-3 defined criteria

  24. Valve malpositioning

    Time frame: Pre-discharge

    As per VARC-3 defined criteria

  25. Conversion to open surgery

    Time frame: Pre-discharge

    As per VARC-3 defined criteria

  26. Unplanned use of mechanical circulatory support (cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), transcatheter pumps or intra-aortic balloon pump (IABP)

    Time frame: Pre-discharge

    As per VARC-3 defined criteria

  27. Implantation of multiple (>1) transcatheter valves during the index hospitalization

    Time frame: Index-procedure

    As per VARC-3 defined criteria

  28. Cardiac structural complications

    Time frame: 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years

    As per VARC-3 defined criteria

  29. Ventricular septal perforation

    Time frame: Pre-discharge

    o Angiographic or echocardiographic evidence of a new septal perforation during or after the TAVI procedure

  30. New onset of atrial fibrillation or atrial flutter

    Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year

    As per VARC-3 defined criteria

  31. Technical success

    Time frame: Post-procedure

    As per VARC-3 defined criteria

  32. Myocardial Infarction

    Time frame: Pre-discharge, 30-day, 1-year, 3-year, and 5-year

    As per VARC-3 defined criteria

  33. Endocarditis

    Time frame: 30-day, 1-year, 3-year, and 5-year

    As per VARC-3 defined criteria

Study contacts

Contact information is provided by the study sponsor or research team.

Ashok Thakkar, PhD

CONTACT

[email protected]

+91-9879443584

Sponsors and collaborators

Lead sponsor

Meril Life Sciences Pvt. Ltd.

Industry

Registry information

Official study 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

Acronym: LANDMARK

Important dates

Study start
2020
Primary completion
2024
Study completion
2033
First posted
Feb 19, 2020
Registry last updated
Apr 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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