A Prospective, Multinational, Multicentre, Open-label, Randomised, Non-inferiority Trial to Compare Safety and Effectiveness of Meril's Myval Transcatheter Heart Valve (THV) Series vs. Contemporary Valves (Edwards's Sapien THV Series and Medtronic's Evolut THV Series) in Patients With Severe Symptomatic Native Aortic Valve Stenosis
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Aortic Valve Stenosis
- Sponsor
- Meril Life Sciences Pvt. Ltd.
- Enrollment
- 988
- Locations
- 54
- Primary Endpoint
- Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The primary objective of this study (LANDMARK) is to compare the safety and effectiveness of the Myval THV Series with Contemporary Valves (Sapien THV Series and Evolut THV Series) in patients with severe symptomatic native aortic valve stenosis.
This study will be done in total 768 subjects (384:384, Myval THV Series vs. Contemporary Valves)
The randomisation will be carried out with an allocation ratio of 1:1 between Myval THV Series vs. Contemporary Valves (Sapien THV Series and Evolut THV Series)
Detailed Description
LANDMARK Trial is a prospective, randomised, multinational, multicentric, open-label non-inferiority trial of total 768 subjects (384:384, Myval THV Series vs. Contemporary Valves) with severe symptomatic native aortic valve stenosis via transfemoral approach. * Device sizes applicable for the Myval THV Series: 20 mm, 21.5 mm, 23 mm, 24.5 mm, 26 mm, 27.5 mm, and 29 mm diameter. * Device sizes applicable for the Sapien 3 THV Series: 20 mm, 23 mm, 26 mm, and 29 mm diameter. * Device sizes applicable for the Evolut THV Series: 23 mm, 26 mm, 29 mm, and 34 mm diameter. A non-randomised nested registry will be conducted to include patients requiring extra-large size of Myval THV series (XL Nested Registry) - Device sizes applicable for the XL Nested Registry: 30.5 mm and 32 mm. A non-randomized registry will include patients implanted with the Myval THV Series (Lead-in Set). - The investigators have to perform a minimum of 2 lead-in cases (non-randomised) under the guidance of the lead-in evaluation committee.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient ≥18 years of age.
- •Patient or their legal representative has provided written informed consent as approved by the Institutional Review Board (IRB)/Institutional Ethics Committee (IEC) of the investigational site to participate in the study.
- •As per local Heart Team assessment, patient is eligible for TAVI and the patient is suitable for implantation with all three study devices.
Exclusion Criteria
- •Patients who are not willing to provide informed consent form, or whose legal heirs object to their participation in the study.
- •Any condition, which in the Investigator's opinion, would preclude safe participation of patient in the study.
Outcomes
Primary Outcomes
Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
Time Frame: 30-day
It is the composite of following: * All-cause mortality * All stroke * Bleeding (Type 3 and 4) * Acute kidney injury (AKI) (Stage 2, 3 and 4) * Major vascular complications * Moderate or severe prosthetic valve regurgitation * Conduction system disturbances resulting in a new PPI
Secondary Outcomes
- Major vascular complications(Pre-discharge, 30-day, and 1-year)
- Bleeding (Type 3 and 4)(Pre-discharge, 30-day, 1-year, 3-year, and 5-year)
- Device success(Pre-discharge and 30-day)
- Clinical efficacy at 30 days(After 30 days of index procedure)
- The combined safety and effectiveness endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)(1-year)
- All stroke(Pre-discharge, 30-day, 1-year, 3-year, and 5-year)
- Acute Kidney Injury (AKI) (Stage 2, 3 and 4)(Pre-discharge, 30-day, and 1-year)
- Valve related long-term clinical efficacy(5-years, 7 years and 10 years)
- Vascular and access related complications(Pre-discharge, 30-day, and 1-year)
- Functional improvement from baseline as measured per([Time frame: Baseline (pre-procedure), 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year], [Time frame: Baseline (pre-procedure), 30-day and 1-year])
- Re-hospitalization(30-day, 1-year, 3-year, and 5-year)
- Valve thrombosis(30-day, 1-year, 3-year, and 5-year)
- Conversion to open surgery(Pre-discharge)
- Implantation of multiple (>1) transcatheter valves during the index hospitalization(Index-procedure)
- Cardiac structural complications(30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years)
- Myocardial Infarction(Pre-discharge, 30-day, 1-year, 3-year, and 5-year)
- Early safety at 30 days(30-day)
- Coronary obstruction requiring intervention(Pre-discharge)
- New permanent pacemaker implantation (As per VARC-3 defined criteria)(Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4-year, 5-year, 7-year, and 10-year)
- All-cause mortality(Pre-discharge, 30-day, 6-month, 1-year, 2-year, 3-year, 4 year, 5-year, 7-year, and 10-year)
- Moderate or severe prosthetic valve regurgitation(Pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year)
- Conduction disturbances and arrhythmias(Pre-discharge, 30-day, 1-year, 3-year, and 5-year)
- Echocardiographic endpoints(Baseline, pre-discharge, 30-day, 1-year, 3-year, 5-year, 7-year, and 10-year)
- Length of index hospital stay(At discharge)
- Health status as evaluated by Quality of Life questionnaires(Baseline (pre-procedure), 30-day, and 1-year)
- Valve malpositioning(Pre-discharge)
- Unplanned use of mechanical circulatory support (cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), transcatheter pumps or intra-aortic balloon pump (IABP)(Pre-discharge)
- Technical success(Post-procedure)
- Endocarditis(30-day, 1-year, 3-year, and 5-year)
- Bioprosthetic valve deterioration(Pre-discharge, 30-day, 1-year, 3-year, and 5-year)
- Patient-prosthesis mismatch(Pre-discharge, 30-day, and 1-year)
- Ventricular septal perforation(Pre-discharge)
- New onset of atrial fibrillation or atrial flutter(Pre-discharge, 30-day, 1-year, 3-year, and 5-year)