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.

N/ANot Yet RecruitingNCT07532317

Meril Life Sciences Pvt. Ltd.778 enrolled

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.

Participants with symptomatic moderate aortic stenosis OR asymptomatic moderate aortic stenosis with evidence of cardiac damage as assessed by echocardiography core lab. Note: The detailed definitions and criterias for moderate AS are provided in inclusion criteria. Clinical and echocardiographic follow-up at: Pre-discharge \[Prior to hospital discharge (within 24 hours of the date of discharge) or maximum of 7 days after index procedure, whichever occurs earlier\] \[Applicable for the TAVI arm only\] 30-day (+ 7 days) \[Applicable for the TAVI arm only\] 6-month (+ 15 days) 1-year (+ 30 days) 1.5-year (+ 30 days) 2-year (+ 30 days) 2.5-year (+ 30 days) 3-year (+ 30 days) 5-year (+ 30 days) 10-year (+ 30 days) Telephonic follow-up at: 4-year (+ 30 days) 6-year (+ 30 days) 7-year (+ 30 days) Note: For participants randomized to the GDMT arm who subsequently undergo AVR or any other intervention at the investigator's discretion, a follow-up visit will be performed at 30 days after the procedure, with an additional follow-up at 1 year (recommended). Thereafter, participants will continue with the remaining scheduled study follow-up visits as per their original study timeline.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

778

Conditions

Eligibility

Sex: ALLMin age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: All participants for this study must meet all of the following inclusion criteria: 1. Participants with ≥ 65 years of age. 2. 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. 3. 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: 1.1.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. 4. Moderate AS participants with symptoms: 1. Evidence of symptoms: I.NYHA class ≥ II# and II.Chronic Dyspnea or III.Angina (CCS ≥ II) or IV.Cardiac Syncope OR 2. 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)(15) or VII.LV dimension(16) or  1. LV systolic diameter \> 4 cm or \> 40 mm for male and \> 3.5 cm or 35 mm for female or 2. LV diastolic diameter \> 5.8 cm or \> 58 mm for male and \> 5.2 cm or 52 mm for female VIII.LV volume(16)  1. LV systolic volume \> 61 mL or cm3 for male and \> 42 mL or cm3 for female or 2. 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: 1. Participants with moderate aortic stenosis undergoing concomitant CABG or surgical intervention on the ascending aorta or another valve. 2. Aortic valve is unicuspid or non-calcified as verified by echocardiography/CT. 3. Renal insufficiency with glomerular filtration rate (GFR) \< 30 mL/min and/or need for renal replacement therapy. 4. Participants with ≥ moderate concomitant aortic regurgitation (≥ 3 grade). 5. Participants with severe aortic stenosis. 6. Moderate or severe mitral/tricuspid regurgitation (≥ 3 grade). 7. Participants with pre-existing mechanical or bioprosthetic aortic valve. 8. Left ventricle ejection fraction ≤ 20%. 9. Severe left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post-TAVI. 10. Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation. 11. Previous stroke with permanent disability (modified Rankin score ≥ 2). 12. 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. 13. Currently participating in an investigational drug or another device study where the primary endpoint is not achieved. 14. Any condition, which in the Investigator's opinion, would preclude safe participation of participants in the study (e.g. psychiatric, alcoholism). 15. TAVI unsuitable via transfemoral route.

Outcomes

Primary Outcomes

All-cause mortality

Time frame: 2-year

Disabling stroke

Time frame: 2 Year

Aortic valve replacement due to advanced valve syndrome (AVS)

Time frame: 2 Year

Heart failure hospitalization

Time frame: 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

Time frame: 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: Time frame: 30-day

Secondary Outcomes

All-cause mortality

VARC-3 defined criteria

Time frame: 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

VARC-3 defined criteria

Time frame: 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)

Stage 2, 3 and 4 (VARC-3 defined criteria)

Time frame: Time Frame: Pre-discharge, 30-day

Bleeding (Type 2, 3 and 4)

VARC-3 defined criteria

Time frame: Time Frame: Predischarge, 30-day

Major vascular complications

VARC-3 defined criteria

Time frame: Time Frame: 30-day

Conduction disturbances and arrhythmias

VARC-3 defined criteria

Time frame: 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)

VARC-3 defined criteria

Time frame: 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: 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: Time Frame: 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year

Myocardial Infarction

VARC-3 defined criteria

Time frame: Time Frame: Predischarge, 30-day, 6-month, 1-year, 1.5-year, 2-year

New York Heart Association (NYHA) functional classification

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

Echocardiographic endpoints

Aortic valve area Indexed aortic valve area Peak aortic velocity Mean aortic gradient Left ventricle (LV) mass index Stroke volume index Left ventricle ejection fraction (LVEF) Diastolic dysfunction ≥ Grade 2 Indexed left atrial volume LV global longitudinal strain (LVGLS) Moderate-severe mitral and tricuspid regurgitation Atrial fibrillation Systolic pulmonary arterial pressure Moderate-severe right ventricular dysfunction LV dimension and LV volume Tricuspid Annular Plane Systolic Excursion (TAPSE) Right Ventricle (RV) Fractional Area Change (RV-FAC) RV global longitudinal strain (RVGLS) RV dimensions Pulsed Doppler S wave

Time frame: 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 Stage 1: Any bioprosthetic valve dysfunction associated with clinically expressive criteria (new-onset or worsening symptoms, LV dilation/hypertrophy/dysfunction, or pulmonary hypertension) or irreversible Stage 3 haemodynamic valve deterioration (HVD) Stage 2: Aortic valve reoperation or re-intervention Stage 3: Valve-related death

Time frame: 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 Stage 1: Morphological valve deterioration Stage 2: Moderate haemodynamic valve deterioration Stage 3: Severe haemodynamic valve deterioration

Time frame: Time Frame: 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year

Aortic bioprosthetic valve dysfunction

VARC-3 defined criteria. This categorized into 1) Structural valve deterioration (SVD), 2) Nonstructural valve dysfunction (NSVD), 3) Thrombosis, and 4) Endocarditis

Time frame: Time Frame: 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year

Heart failure hospitalization

Time frame: 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 (KCCQ)

Time frame: Time Frame: Screening, 1-year, 2-year, At time of conversion to AVR from GDMT arm

Moderate or severe prosthetic valve regurgitation

VARC-3 defined criteria

Time frame: 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: 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

VARC-3 defined criteria

Time frame: 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: 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

VARC-3 defined criteria

Time frame: Time Frame: At exit from procedure room

Device success

VARC-3 defined criteria

Time frame: Time Frame: 30-day

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.

Overview

Conditions

Interventions

Eligibility

Locations (62)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts