TRI-FR : Multicentric Randomized Evaluation of Tricuspid Valve Percutaneous Repair System (Clip for the Tricuspid Valve) in the Treatment of Severe Secondary Tricuspid Disorders
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 300
- 试验地点
- 29
- 主要终点
- Milton Packer clinical composite score
研究概览
简要总结
Tricuspid regurgitation (TR) is a long-overdue valvular pathology. Its prevalence is significant and increasing with the aging of the population. It is often a consequence of chronic left cardiac pathologies or atrial fibrillation. Surgical treatment is recommended in severe symptomatic TR or when the tricuspid annulus is dilated with TR identified prior to scheduled left heart valve surgery. TR are mainly secondary (complicating left heart disease, pulmonary hypertension, atrial fibrillation and atrial dilatation) and pose a difficult problem related to the prognosis. The risk of death or hospitalization is high under medical treatment. Nevertheless, the surgical results are disappointing with significant morbidity and mortality, which are increased by associated comorbidities that are frequent in these sorts of patients. The benefit-risk assessment of surgery is limited by multiple confounders.
This justifies the evaluation of alternative methods aimed at correcting TR with less interventional risk.
The Clip for the tricuspid valve has been evaluated in the TRILUMINATE trial (inclusion of 85 patients with moderate-to-severe symptomatic TR with a 6-month follow-up). The Triclip system appears to be safe and effective at reducing tricuspid regurgitation by at least one grade. This reduction could translate to significant clinical improvement at 6 months post-procedure. It justified the European Conformity (CE) mark obtention.
A very similar system for the mitral valve (Mitraclip) was previously tested in the randomized EVEREST II study against conventional surgery. The results of the EVEREST II trial justified the recourse to percutaneous edge-to edge mitral repair in patients with primary mitral regurgitation when the patient is contraindicated to conventional surgery.
The Mitra-FR study made it possible to study the role of Mitraclip for treating patient suffering from a secondary mitral insufficiency. It leads to the implementation of this technique in selected patients.
For secondary TR, several series underscored its prevalence and its clinical consequences. TR treatment justifies the proposal for a randomized study. As a matter of fact, evidence for treating are seriously lacking. Surgical surveys report hospital mortality ~ 8.8%. It, therefore, seems necessary to conduct a study as robust as possible to evaluate the contribution of clip for the tricuspid valve (as an innovative percutaneous technique) compared to conventional pharmacological treatment in patients who are unsuitable for a surgical isolated correction of the TR and who has suitable anatomy for clip for the tricuspid valve. It will be necessary to demonstrate clinical, functional (quality of life), echocardiographic and biological benefit of the percutaneous treatment vs optimized medical treatment alone.
详细描述
The principal objective is to demonstrate, over a period of 12-month after randomization, that, on the Packer composite clinical endpoint (CCS) (combining NYHA class, patient global assessment (PGA) and major cardio-vascular events), the tricuspid valve percutaneous repair strategy with clip for the tricuspid valve is superior to best (optimized) medical treatment (BMT) in symptomatic patients with at least severe secondary TR. The Packer clinical composite score is eventually a three-level ordered categorical endpoint, each randomized patient being classifying as improved, unchanged, or worsen, depending on the clinical response over the follow-up period and at 12 months.
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
- •Pre-Inclusion Criteria:
- •Age ≥ 18 years
- •Symptomatic secondary (at least) severe TR (Carpentier Type IIIB (restrictive) and / or I (tricuspid annulus dilation)) stable for at least 30 days
- •NYHA functional class II to IV without cirrhosis and/or ascites
- •Signs of heart failure in the previous 12-months with or without having been hospitalized
- •Stable optimized medical and/or interventional treatment
- •Ineligible for corrective action on the valve by surgical approach after a specialized multidisciplinary consultation ("heart team") including at least a cardio-thoracic surgeon, an interventional cardiologist, an imaging-cardiologist and an Anesthesiologist).
- •Signature of an informed consent
- •Definitive Inclusion Criteria:
- •Central core-laboratory analysis : TR characterized before Implantation by at least one of the following criteria:
- •Regurgitation volume > 45 mL / beat
- •Surface of the regurgitant orifice > 40 mm²
- •Vena contracta> 7mm
- •Gap between leaflets ≤ 10 mm (at the presumed location of the clip)
- •Then after the TR severity grading; the Clinical eligibility Committee will valid the inclusion.
- •Non Inclusion Criteria:
- •Patient treated with Mitraclip or other percutaneous approach on the mitral valve in the past 3-month
- •Any prior tricuspid valve procedure that would interfere with placement of the Triclip device
- •Tricuspid valve leaflet anatomy which may preclude clip implantation, proper clip positioning on the leaflets or sufficient reduction in TR. This may include:
- •Tricuspid valve anatomy not evaluable by TTE and TEE
- •Active endocarditis
- •Evidence of calcification in the grasping area
- •Evidence of stenosis (mean pressure gradient > 5 mmHg or surface area ≤1cm²
- •Presence of a severe coaptation defect (> 1cm) of the tricuspid leaflets
- •Severe leaflet defect(s) preventing proper device placement
- •Epstein anomaly - identified by having a normal annulus position while the valve leaflets are attached to the walls and septum of the right ventricle
- •Myocardial infarction or coronary bypass surgery in the past 3-month
- •Left ventricular ejection fraction ≤35%
- •Cardiac Resynchronization therapy for less than 3-month and patients having a TR that is clearly related to the right ventricular lead positioning
- •Cardioversion for less than 6 weeks
- •Life expectancy irrespective of the valvular heart disease <1 year (due to co-morbidities)
- •Other scheduled cardiac surgery (including registration in cardiac transplant list)
- •Coronary angioplasty in the preceding month
- •Current infection requiring prescription of antibiotics
- •End-stage renal failure (dialysis patient)
- •Severe hepatic insufficiency (disruption of liver metabolism associated with coagulation disorders (factor V <50%))
- •Stroke in the previous 3-month
- •Uncontrolled pre- capillary pulmonary hypertension (right catheterization required) (systolic pulmonary pressure > 60 mmHg)
- •Tricuspid prosthetic valve
- •Pace maker lead or ICD lead that would prevent appropriate placement of the Triclips
- •Nitinol allergy
- •Contraindication, allergy or hypersensibility to dual anti-platelet and anticoagulant therapy
- •Ongoing infection requiring antibiotic therapy
- •Evidence of intra vascular or intra cardiac thrombus
- •Patient who are included in another research protocol
- •Protected person (adults legally protected (under judicial protection, guardianship or supervision), person deprived of their liberty, pregnant woman, lactating woman and minor)
- •Absence of coverage by a social security scheme
排除标准
- 未提供
结局指标
主要结局
Milton Packer clinical composite score
时间窗: 12 months
Milton Packer clinical composite score classifies each patient into 1 of 3 categories (improved, worsened, unchanged), and is determined aggregating evaluation functional using NYHA class, quality of life score using patient global assessment and number of major cardio-vascular events
次要结局
- number of participants with tricuspid valve surgery(12 months)
- number of participants with all-cause mortality(12 months)
- number of cardiovascular death(6 and 12 months)
- echocardiography parameters(6 and 12 months)
- assessment of quality of life improvement(0 and 12 months)
- functional evaluation(6 and 12 months)
- Incremental Cost-Effectiveness Ratio expressed as cost per QALY(12 and 24 months)
- walking distance(6 and 12 months)
- rate of heart failure hospitalizations(12 months)
- severity of the Tricuspid Regurgitation (TR)(6 and 12 months)
- overall survival(6 and 12 months)
- number of major cardiovascular events(6 and 12 months)
- quality of life score(6 and 12 months)
- biological parameters(6 and 12 months)