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.
Participants with symptomatic moderate aortic stenosis OR asymptomatic moderate aortic stenosis with evidence of cardiac damage as assessed by echocardiography core lab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
778
Myval THV Series will include Myval/Myval Octacor/ OctaPro/OctaPro+ THV or any subsequent advanced version commercially available at the investigator site.
Primary Efficacy Endpoint
It is the composite of following: All-cause mortality, Disabling stroke, Aortic valve replacement due to advanced valve syndrome (AVS), Heart failure hospitalization, Deterioration in quality of life by Kansas City Cardiomyopathy Questionnaire (KCCQ) at 2 years or at the time of conversion to AVR in the GDMT arm.
Time frame: 2-year
All-cause mortality
As per VARC-3 defined criteria
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
As per VARC-3 defined criteria
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)
As per VARC-3 defined criteria
Time frame: Pre-discharge, 30-day
Bleeding (Type 2, 3 and 4)
As per VARC-3 defined criteria
Time frame: Predischarge, 30-day
Major vascular complications
As per VARC-3 defined criteria
Time frame: 30-day
Conduction disturbances and arrhythmias
As per VARC-3 defined criteria
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)
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As per VARC-3 defined criteria
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
Initiation of CRT (Cardiac Resynchronization Therapy Pacemaker or Defibrillator with Cardiac Resynchronization Therapy) as clinically indicated by the treating cardiologist.
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
As per VARC-3 defined criteria
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
Echocardiographic endpoints
Time frame: Screening, Pre-discharge, 30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10- year
Bioprosthetic valve failure
VARC-3 defined criteria
Time frame: 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year
Bioprosthetic valve deterioration
VARC-3 defined criteria
Time frame: 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year
Aortic bioprosthetic valve dysfunction
As per VARC-3 defined criteria
Time frame: 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year
Heart failure hospitalization
As per VARC-3 defined criteria
Time frame: 30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year
Kansas City Cardiomyopathy Questionnaire
Overall Summary Score \< 45 or decline from baseline of \>10 point (Unfavorable Outcome) Score Interpretation: 0 to 25: Very poor to poor health 25 to 49: Poor to fair health 50 to 74: Fair to good health 75 to 100: Good to excellent health
Time frame: Screening, 1-year, 2-year, At time of conversion to AVR from GDMT arm
Moderate or severe prosthetic valve regurgitation
As per VARC-3 defined criteria
Time frame: Screening, Pre-discharge, 30-day, 6-month, 1- year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year
N-Terminal Pro B-type Natriuretic Peptide (NT-ProBNP) or BNP
Time frame: Screening, Pre-discharge, 30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year
New onset of atrial fibrillation or atrial flutter
As per VARC-3 defined criteria
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 or reintervention
Aortic valve replacement or reintervention is defined as any surgical or transcatheter procedure performed to replace the native aortic valve with a prosthetic valve or to treat dysfunction of a previously implanted prosthetic aortic valve. This includes surgical aortic valve replacement (SAVR), transcatheter aortic valve implantation (TAVI), valve-in-valve TAVI, redo TAVI, or surgical replacement of a previously implanted transcatheter or surgical valve.
Time frame: 30-day, 6- month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year
Technical success
As per VARC-3 defined criteria
Time frame: At exit from procedure room
Device success
As per VARC-3 defined criteria
Time frame: 30-day