Moderate Aortic Stenosis
Conditions
Keywords
Cardiac Damage, Effectiveness, Guideline Directed Medical Therapy, Left ventricular ejection fraction, Low-flow, low-gradient aortic stenosis, Transcatheter Heart Valve THV), Moderate aortic stenosis, Myval THV series, Myval THV, Myval Octacor THV, Myval OctaPro THV, Myval OctaPro+ THV
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.
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
DEVICETranscatheter 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.
Sponsors
Meril Life Sciences Pvt. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
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 * 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. 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) or VII.LV dimension 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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Endpoint | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | As per VARC-3 defined criteria |
| All stroke | Pre-discharge, 30- day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year | As per VARC-3 defined criteria |
| Acute Kidney Injury (AKI) | Pre-discharge, 30-day | As per VARC-3 defined criteria |
| Bleeding (Type 2, 3 and 4) | Predischarge, 30-day | As per VARC-3 defined criteria |
| Major vascular complications | 30-day | As per VARC-3 defined criteria |
| 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 | As per VARC-3 defined criteria |
| 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 | As per VARC-3 defined criteria |
| 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 | Initiation of CRT (Cardiac Resynchronization Therapy Pacemaker or Defibrillator with Cardiac Resynchronization Therapy) as clinically indicated by the treating cardiologist. |
| 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 | As per VARC-3 defined criteria |
| 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 | VARC-3 defined criteria |
| Bioprosthetic valve deterioration | 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year | VARC-3 defined criteria |
| Aortic bioprosthetic valve dysfunction | 1-year, 1.5-year, 2-year, 2.5-year, 3-year, 5-year and 10-year | As per VARC-3 defined criteria |
| Heart failure hospitalization | 30-day, 6-month, 1-year, 1.5-year, 2-year, 2.5-year, 3-year and 5-year | As per VARC-3 defined criteria |
| Kansas City Cardiomyopathy Questionnaire | Screening, 1-year, 2-year, At time of conversion to AVR from GDMT arm | 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 |
| 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 | As per VARC-3 defined criteria |
| 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 | As per VARC-3 defined criteria |
| 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 | 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. |
| Technical success | At exit from procedure room | As per VARC-3 defined criteria |
| Device success | 30-day | As per VARC-3 defined criteria |
Contacts
CONTACTDr.Ashokkumar Thakkar, PhD. Clinical Pharmacology
Outcome results
None listed