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.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 778
- 试验地点
- 62
- 主要终点
- All-cause mortality
研究概览
简要总结
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.
详细描述
Participants with symptomatic moderate aortic stenosis OR asymptomatic moderate aortic stenosis with evidence of cardiac damage as assessed by echocardiography core lab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Guideline-directed medical therapy
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 Implantation
干预措施: Transcatheter aortic valve Implantation (Device)
结局指标
主要结局
All-cause mortality
时间窗: 2-year
Disabling stroke
时间窗: 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
时间窗: 2 Year
Aortic valve replacement due to advanced valve syndrome (AVS)
时间窗: 2 Year
Heart failure hospitalization
时间窗: 2 Year
Safety Assessment
时间窗: Time frame: 30-day
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
Aortic valve replacement due to advanced valve syndrome
时间窗: 2 Year
Deterioration in quality of life by Kansas City Cardiomyopathy Questionnaire at 2 years or at the time of conversion to AVR in the GDMT arm
时间窗: 2 Year
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
Primary Efficacy Endpoint
时间窗: 2-year
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.
次要结局
- Kansas City Cardiomyopathy Questionnaire (KCCQ)(Time Frame: Screening, 1-year, 2-year, At time of conversion to AVR from GDMT arm)
- 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)
- 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)
- 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(Time Frame: 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year)
- Bioprosthetic valve deterioration(Time Frame: 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year)
- Aortic bioprosthetic valve dysfunction(Time Frame: 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year)
- Heart failure hospitalization(Time Frame: 30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year)
- Moderate or severe prosthetic valve regurgitation(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(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(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(Time Frame: At exit from procedure room)
- Device success(Time Frame: 30-day)
- Kansas City Cardiomyopathy Questionnaire(Time Frame: Screening, 1-year, 2-year, At time of conversion to AVR from GDMT arm)
- All-cause mortality(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(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)(Pre-discharge, 30-day)
- Bleeding (Type 2, 3 and 4)(Predischarge, 30-day)
- Major vascular complications(30-day)
- Conduction disturbances and arrhythmias(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)(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(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(6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year)
- Myocardial Infarction(Predischarge, 30-day, 6-month, 1-year, 1.5-year, 2-year)
- New York Heart Association (NYHA) functional classification(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(Screening, 30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year)
- Echocardiographic endpoints(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(1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year)
- Bioprosthetic valve deterioration(1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year)
- Aortic bioprosthetic valve dysfunction(1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year)
- Heart failure hospitalization(30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year)
- Kansas City Cardiomyopathy Questionnaire(Screening, 1-year, 2-year, At time of conversion to AVR from GDMT arm)
- Moderate or severe prosthetic valve regurgitation(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(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(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(30-day, 6- month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year)
- Technical success(At exit from procedure room)
- Device success(30-day)