A Prospective, Multinational, Multicentre, Open-label, Randomized Trial to Evaluatesafety and Effectiveness of Meril's Myval Transcatheter Heart Valve (THV) Series Compared toGuideline-Directed Medical Therapy (GDMT) in Participants With Moderate Aortic Stenosis.

NCT07532317 | Not Yet Recruiting DMC

• 1 other identifier: MLS/MYV/LANDMARK 2
• Study Type: interventional
• Target: 778
• Locations: 17 countries
• Sites: 59

Brief Summary

The primary objective of this trial is to evaluate the safety and effectiveness of Meril's Myval THV series in comparison to Guideline-Directed Medical Therapy in participants with moderate aortic stenosis. The trial includes a total of 778 participants (389:389) from approximately 50 investigator sites globally.

Conditions

Moderate Aortic Valve Stenosis

Keywords

LANDMARK 2; Moderate Aortic Valve Stenosis; GDMT

Outcome Measures

Primary Outcomes (6)

• All-cause mortality

  2-year

• Disabling stroke

  2 Year

• Aortic valve replacement due to advanced valve syndrome (AVS)

  2 Year

• Heart failure hospitalization

  2 Year

• Deterioration in quality of life by Kansas City Cardiomyopathy Questionnaire (KCCQ) at2 years or at the time of conversion to AVR in the GDMT arm

  2 Year

• Safety Assessment

  Safety Assessment (Applicable for TAVI arm only): Early Safety as per Valve Academic Research Consortium-3 (VARC-3) defined criteria It is the composite of following: Freedom from all cause mortality Freedom from all stroke Freedom from VARC type 2-4 bleeding Freedom from major vascular, access-related, or cardiac structural complication Freedom from acute kidney injury (stage 3 or 4) Freedom from moderate or severe aortic regurgitation Freedom from new permanent pacemaker due to procedure-related conduction abnormalities Freedom from surgery or intervention related to the device

  Time frame: 30-day

Secondary Outcomes (24)

• All-cause mortality

  Time Frame: Predischarge, 30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 4- year, 5-year, 6-year, 7-year and 10-year

• All stroke

  Time Frame: Pre-discharge, 30- day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year

• Acute Kidney Injury (AKI)

  Time Frame: Pre-discharge, 30-day

• Bleeding (Type 2, 3 and 4)

  Time Frame: Predischarge, 30-day

• Major vascular complications

  Time Frame: 30-day

Study Arms (2)

Guideline-directed medical therapy

NO INTERVENTION

Participants in the GDMT arm will receive guideline-directed medical therapy based on their clinical condition and in accordance with hospital standard practice based on European Society of Cardiology (ESC)/ European Association for Cardio-Thoracic Surgery (EACTS) 2023 \& 2021 and American Heart Association/ American College of Cardiology/ Heart Failure Society of America (AHA/ACC/HFSA) 2022 Heart Failure (HF) guidelines and its subsequent updates(\[ McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JG. 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC. European heart journal. 2023 Oct 1;44(37):3627-39.\],\[ Heidenreich PA, Bozkurt B, Aguilar D,

Transcatheter Aortic Valve Replacement

OTHER

Transcatheter Aortic Valve Replacement: Myval THV Series will include Myval/Myval Octacor/OctaPro/OctaPro+ THV or any subsequent advanced version commercially available at the investigator site.

Device: Transcatheter aortic valve replacement

Interventions

Transcatheter aortic valve replacement DEVICE

Myval THV Series will include Myval/Myval Octacor/OctaPro/OctaPro+ THV or any subsequent advanced version commercially available at the investigator site. Participants in the GDMT arm will receive guideline-directed medical therapy based on their clinical condition and in accordance with hospital standard practice based on European Society of Cardiology / European Association for Cardio-Thoracic Surgery (EACTS) and American Heart Association/ American College of Cardiology/ Heart Failure Society of America (AHA/ACC/HFSA) Heart Failure (HF) guidelines and its subsequent updates

Transcatheter Aortic Valve Replacement

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Participants with ≥ 65 years of age.
• Participant has provided written informed consent as approved Institutional Review Board (IRB)/Independent Ethics Committee (IEC)/Ethics Committee (EC) of the investigational site to participate in the study.
• Participant with moderate aortic stenosis, defined as one of the following(10)
• Peak aortic jet velocity (Vmax) ≥ 3.0 m/s and \< 4.0 m/s, or
• Mean pressure gradient ≥ 25 mmHg and \< 40 mmHg AND
• The participant must meet one of the following categories:
• AVA \> 1.0 - ≤ 1.5 cm²; OR 1.2.AVA ≤ 1.0 cm2 (or AVAi ≤ 0.6 cm2/m2) 3.2.1 Left Ventricular Function and Flow Profile: It is defined as participants with peak aortic jet velocity (Vmax) ≥ 3.0 and \< 4.0 m/s or mean pressure gradient ≥ 25 and \< 40 mmHg, and in the presence of aortic valve area (AVA) ≤ 1.0 cm² (or AVAi ≤ 0.6 cm²/m²)
• The participant must meet one of the following categories:
• a.Normal-Flow, Preserved LVEF:\*
• Stroke Volume Index (SVi \> 35 ml/m²) and LVEF ≥ 50% then, perform CT aortic valve calcium score to confirm true moderate AS: \< 1200 AU (female) or \< 2000 AU (male) OR b.Low-Flow, Preserved LVEF:
• SVi ≤ 35 ml/m² and LVEF ≥ 50%, then perform CT aortic valve calcium score to confirm true moderate AS: \< 1200 AU (female) or \< 2000 AU (male) OR c.Low-Flow, Reduced LVEF:
• SVi ≤ 35 ml/m² and LVEF \< 50%, then confirm contractile reserve on dobutamine stress echocardiography (DSE)\^, defined as a ≥ 20% increase in stroke volume with; I.AVA \> 1.0 and ≤ 1.5 cm2 or II.AVA \> 1.0 cm2 then perform CT aortic valve calcium score to confirm true moderate AS: \< 1200 AU (female) or \< 2000 AU (male) \^ If DSE is not feasible or inconclusive, CT calcium scoring will be considered, with thresholds of \< 1200 AU for female and \< 2000 AU for male to identify Moderate AS participants. \*Not applicable for asymptomatic participants as asymptomatic with SVi \> 35 are excluded.
• Moderate AS participants with symptoms:
• Evidence of symptoms:
• I.NYHA class ≥ II# and II.Chronic Dyspnea or III.Angina (CCS ≥ II) or IV.Cardiac Syncope OR

You may not qualify if:

• Participants with moderate aortic stenosis undergoing concomitant CABG or surgical intervention on the ascending aorta or another valve.
• Aortic valve is unicuspid or non-calcified as verified by echocardiography/CT.
• Renal insufficiency with glomerular filtration rate (GFR) \< 30 mL/min and/or need for renal replacement therapy.
• Participants with ≥ moderate concomitant aortic regurgitation (≥ 3 grade).
• Participants with severe aortic stenosis.
• Moderate or severe mitral/tricuspid regurgitation (≥ 3 grade).
• Participants with pre-existing mechanical or bioprosthetic aortic valve.
• Left ventricle ejection fraction ≤ 20%.
• Severe left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post-TAVI.
• Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation.
• Previous stroke with permanent disability (modified Rankin score ≥ 2).
• Life expectancy \< 24 months due to non-cardiac co-morbid conditions including carcinomas, chronic liver disease, chronic renal disease or chronic end-stage pulmonary disease.
• Currently participating in an investigational drug or another device study where the primary endpoint is not achieved.
• Any condition, which in the Investigator's opinion, would preclude safe participation of participants in the study (e.g. psychiatric, alcoholism).
• TAVI unsuitable via transfemoral route.

Sponsors & Collaborators

• Meril Life Sciences Pvt. Ltd.: lead

Study Sites (62)

John Hunter Hospital

Newcastle, New South Wales, Australia

Location

Prince Charles Hospital

Brisbane, Queensland, Australia

Location

Victorian Heart Hospital

Melbourne, Victoria, Australia

Location

Republican Scientific and Practical Center of Cardiology (RSPC Cardiology)

Minsk, Minsk Oblast, 220036, Belarus

Location

Instituto Dante Pazzanese de Cardiologia

São Paulo, São Paulo, 04012-909, Brazil

Location

Rigshospitalet

Copenhagen, Capital Region, 2100, Denmark

Location

Rigshospitalet, Copenhagen University Hospital

Copenhagen, Capital Region of Denmark (Hovedstaden), 2100, Denmark

Location

North Estonia Medical Centre (Põhja-Eesti Regionaalhaigla)

Tallinn, Harju, 13419, Estonia

Location

Turku University Hospital (Tyks), Heart Centre

Turku, Southwest Finland, 20521, Finland

Location

Turku University Hospital

Turku, Southwest Finland, 20521, Finland

Location

Médipôle Lyon-Villeurbanne

Villeurbanne, Auvergne-Rhône-Alpes, 69100, France

Location

Centre Hospitalier Universitaire de Rennes

Rennes, Brittany Region, 35033, France

Location

Centre Hospitalier Universitaire de Tours

Tours, Centre-Val de Loire, 37044, France

Location

Hôpital Privé Jacques Cartier (ICPS - Institut Cardiovasculaire Paris Sud)

Massy, Essonne, 91300, France

Location

Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg

Strasbourg, Grand Est, 67091, France

Location

Clinique Pasteur - Toulouse

Toulouse, Haute-Garonne, 31300, France

Location

Centre Hospitalier Régional Universitaire de Lille

Lille, Hauts-de-France, 59037, France

Location

Centre Hospitalier Universitaire de Bordeaux

Bordeaux, Nouvelle-Aquitaine, France

Location

Centre Hospitalier Universitaire de Toulouse - Hôpital Rangueil

Toulouse, Occitanie, 31059, France

Location

Hôpital de la Timone - Assistance Publique Hôpitaux de Marseille

Marseille, Provence-Alpes-Côte d'Azur Region, 13005, France

Location

Institut Arnault Tzanck

Saint-Laurent-du-Var, Provence-Alpes-Côte d'Azur Region, 06700, France

Location

Hôpital Henri-Mondor - Assistance Publique Hôpitaux de Paris

Créteil, Île-de-France Region, 94010, France

Location

Centre Cardiologique du Nord

Saint-Denis, Île-de-France Region, 93200, France

Location

Universitäts-Herzzentrum Freiburg - Bad Krozingen

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Universitätsklinikum Regensburg

Regensburg, Bavaria, 93053, Germany

Location

Kerckhoff Klinik GmbH

Bad Nauheim, Hesse, 61231, Germany

Location

Städtisches Klinikum Braunschweig

Braunschweig, Lower Saxony, 38118, Germany

Location

Herzzentrum Dresden GmbH Universitätsklinik

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

IRCCS Ospedale San Raffaele

Milan, Milan, 20132, Italy

Location

IRCCS Ospedale Galeazzi - Sant'Ambrogio

Milan, Milan, 20157, Italy

Location

IRCCS Policlinico San Donato

San Donato Milanese, Milan, 20097, Italy

Location

Radboud University Medical Center

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Amphia Hospital

Breda, North Brabant, 4818 CK, Netherlands

Location

Catharina Hospital

Eindhoven, North Brabant, 5623 EJ, Netherlands

Location

OLVG

Amsterdam, North Holland, 1091 AC, Netherlands

Location

Erasmus Medical Center

Rotterdam, South Holland, 3015 GD, Netherlands

Location

St. Antonius Hospital

Nieuwegein, Utrecht, 3435 CM, Netherlands

Location

University Medical Center Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

Location

Auckland City Hospital

Auckland, Auckland, 1023, New Zealand

Location

Waikato Hospital

Hamilton, Waikato Region, 3204, New Zealand

Location

University Clinic of Cardiology Skopje

Skopje, Grad Skopje, 1000, North Macedonia

Location

Oslo University Hospital - Rikshospitalet

Oslo, Oslo County, 0372, Norway

Location

Middle Slovak Institute of Cardiovascular Diseases (SÚSCCH)

Banská Bystrica, Banská Bystrica Region, 974 01, Slovakia

Location

University Medical Centre Ljubljana

Ljubljana, Osrednjeslovenska, 1000, Slovenia

Location

Netcare Sunninghill Hospital

Sandton, Gauteng, 2191, South Africa

Location

Hospital Universitario Virgen del Rocío

Seville, Andalusia, 41013, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Aragon, 50009, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Hospital Clínico Universitario de Salamanca

Salamanca, Castille and León, 37007, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, Castille and León, 47003, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, Córdoba, 14004, Spain

Location

Hospital Álvaro Cunqueiro

Vigo, Galicia, 36213, Spain

Location

Hospital Universitario de Gran Canaria Doctor Negrín

Las Palmas de Gran Canaria, Las Palmas, 35010, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, Valencia, 46026, Spain

Location

Uppsala University Hospital

Uppsala, Uppsala County, 75185, Sweden

Location

Universitätsspital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

Barts Heart Centre, St Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

Location

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Related Links

• A study showing that early aortic valve surgery significantly reduces all-cause death compared to medical treatment in patients with moderate AS and left ventricular systolic dysfunction (LVSD)
• The comprehensive US clinical practice guidelines for the prevention, diagnosis, and management of patients with heart failure, establishing the pillars of guideline-directed medical therapy (GDMT)
• The industry-standard update for clinical endpoint definitions in aortic valve research, ensuring consistent reporting for transcatheter and surgical therapies.
• An international multicenter study demonstrating that second-generation TAVR devices achieve favorable procedural results and clinical outcomes in patients with bicuspid aortic valve stenosis, comparable to those with tricuspid anatomy.
• A major study confirming that TAVR is a durable and effective alternative to surgery for high-risk patients, with 5-year data showing no significant difference in all-cause mortality or stroke compared to SAVR.
• A vital consensus document providing standardized technical rules and clinical algorithms for grading the severity of aortic stenosis using various echocardiographic parameters.
• A comprehensive review of current evidence showing that moderate AS is associated with increased cardiovascular events and mortality, while discussing the potential benefits of early aortic valve replacement (AVR).
• A propensity-matched study of nearly 1,000 patients showing that moderate AS is associated with significantly increased mortality compared to patients without AS, regardless of whether the heart's pumping function (ejection fraction) is preserved or redu
• Boljevic D, Bojic M, Farkic M, et al. Early Outcomes of a Next-Generation Balloon-Expandable Transcatheter Heart Valve - The Myval System: A Single-Center Experience From Serbia. Journal of Cardiology and Cardiovascular Medicine. 2023.

MeSH Terms

Interventions

Transcatheter Aortic Valve Replacement

Intervention Hierarchy (Ancestors)

Heart Valve Prosthesis Implantation; Cardiac Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Prosthesis Implantation; Thoracic Surgical Procedures

Study Officials

• Prof. Patrick Serruys, MD, PhD, FACC, FESC

  National University of Ireland, Galway, Ireland

  STUDY DIRECTOR

• Prof. Andreas Baumbach, MD, FESC, FRCP

  Barts Heart Center, London, UK

  STUDY CHAIR

Central Study Contacts

Dr.Ashokkumar Thakkar, PhD. Clinical Pharmacology

CONTACT

+91-9879443584; landmark.2@merillife.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2026
• First Posted: April 15, 2026
• Study Start (Estimated): May 17, 2026
• Primary Completion (Estimated): May 12, 2028
• Study Completion (Estimated): May 12, 2038
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (7); BR (1); AU (3); ZA (1); FR (13); CH (1); GB (1); ES (13); DE (6); NO (1); SL (1); IT (3); BE (1); SE (1); DK (2); FI (2); NZ (2)