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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 988
- 试验地点
- 99
- 主要终点
- Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
研究概览
简要总结
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)
详细描述
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).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Contemporary Valves
- Sapien THV Series will consist of Sapien 3/Sapien 3 Ultra THVs or any subsequent advanced version commercially available at the study site.
- Evolut THV Series will include Evolut R/Evolut PRO THVs or any subsequent advanced version commercially available at the study site.
This treatment arm will be assigned to 384 / 768 subjects enrolled in a study.
干预措施: Contemporary Valves (Sapien THV Series and Evolut THV Series) (Device)
Myval THV Series XL Nested Registry
A non-randomised, nested registry of patients with anatomy of native aortic annulus suitable to be implanted with extra-large size of Myval THV series (30.5mm or 32mm) as per Heart Team assessment/Investigator's discretion is designed. The objective of this registry is to assess the safety and effectiveness of extra-large sizes of Myval THV series. Approximately 100 patients will be recruited from approximately 30 participating centres in LANDMARK Trial
干预措施: Myval THV Series (Device)
Myval THV Series Lead-in Set
The Lead-in Set aims to ensure investigators adhere to protocol requirements related to the Myval THV Series device, including imaging and procedural guidelines. Investigators should be independent before enrolling study subjects, allowing for valuable feedback for initial safety assessments. Each investigator must conduct at least two non-randomized lead-in cases under the guidance of an evaluation committee. Lead-in subjects will only receive the study device, and if implantation fails, standard care will be provided. These subjects will not be included in primary or secondary endpoint analyses but will undergo descriptive analysis. Unique numbers will be assigned to all lead-in subjects, and the committee will evaluate outcomes and site independence for future trial recruitment.
干预措施: Myval THV Series (Device)
Myval THV Series
Myval THV Series will include Myval/Myval Inception THVs or any subsequent advanced version commercially available at the study site.
This treatment arm will be assigned to 384 / 768 subjects enrolled in a study.
干预措施: Myval THV Series (Device)
结局指标
主要结局
Primary Combined Safety and Effectiveness Endpoint as defined by the Valve Academic Research Consortium-3 (VARC-3)
时间窗: 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
次要结局
- 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)