Comparison of Myval THV Series With Guideline-Directed Medical Therapy in Participants With Moderate Aortic Stenosis

Official title

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

Overview

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.

Detailed description

Participants with symptomatic moderate aortic stenosis OR asymptomatic moderate aortic stenosis with evidence of cardiac damage as assessed by echocardiography core lab.

Interventions

• Device Transcatheter aortic valve Implantation
  Myval THV Series will include Myval/Myval Octacor/ OctaPro/OctaPro+ THV or any subsequent advanced version commercially available at the investigator site.

Primary outcome measures

• Primary Efficacy Endpoint [Time frame: 2-year]

Secondary outcome measures (12)

• 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]
• Conduction disturbances and arrhythmias [Time frame: Pre-discharge, 30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5- year, 3-year and 5-year]
• New Permanent Pacemaker Implantation (PPI) [Time frame: Pre-discharge, 30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year]
• Proportion of participants requiring initiation of Cardiac Resynchronization Therapy [Time frame: Pre-discharge, 30-day, 6- month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year]
• Aortic valve replacement due to advanced valve syndrome [Time frame: 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year]
• Myocardial Infarction [Time frame: Predischarge, 30-day, 6-month, 1-year, 1.5-year, 2-year]
• New York Heart Association (NYHA) functional classification [Time frame: Screening, Pre-discharge, 30-day, 6-month, 1-year, 1.5-year, 2- year, 2.5-year, 3-year and 5-year]
• Six-minute walk test [Time frame: Screening, 30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year]

Eligibility criteria

Inclusion criteria

All participants for this study must meet all of the following inclusion criteria:

• 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

• 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:

3.1.AVA > 1.0 - ≤ 1.5 cm²; OR

3.2.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

• Asymptomatic moderate AS participants with at least one of the evidence of cardiac damage/dysfunction:

I.Participant with left ventricle ejection fraction ≤ 50% or

II.Diastolic dysfunction ≥ Grade II or

III.Stroke Volume Index ≤ 35 ml/m² or

IV.Persistent Atrial Fibrillation (AF) lasting from past 6 months or Paroxysmal Atrial Fibrillation episode within 6 months prior to consent or

V.NT-proBNP ≥ 200 pg/ml or ng/l or ≥ 200000 µg/l (or BNP ≥ 50 pg/ml or ng/l or ≥ 50000 µg/l) or

VI.LV mass index > 95 g/m² for female and > 115 g/m² for male (To detect LV hypertrophy) or

VII.LV dimension or

• LV systolic diameter > 4 cm or > 40 mm for male and > 3.5 cm or 35 mm for female or
• LV diastolic diameter > 5.8 cm or > 58 mm for male and > 5.2 cm or 52 mm for female

VIII.LV volume

• LV systolic volume > 61 mL or cm3 for male and > 42 mL or cm3 for female or
• LV diastolic volume > 150 mL or cm3 for male and > 106 mL or cm3 for female

• Only 10% of total study participants with NYHA class IV will be included in the trial.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07532317 · MLS/MYV/LANDMARK 2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗