Evaluation of Tricuspid Valve Percutaneous Repair System in the Treatment of Severe Secondary Tricuspid Disorders
Evaluation of Tricuspid Valve Percutaneous Repair System in the Treatment of Severe Secondary Tricuspid Disorders
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.
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.
Inclusion Criteria:

 Pre-Inclusion Criteria:

 1. Age > 18 years

 2. Symptomatic secondary (at least) severe TR (Carpentier Type IIIB (restrictive) and /
 or I (tricuspid annulus dilation)) stable for at least 30 days

 3. NYHA functional class II to IV without cirrhosis and/or ascites

 4. Signs of heart failure in the previous 12-months with or without having been
 hospitalized

 5. Stable optimized medical and/or interventional treatment

 6. 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).

 7. Signature of an informed consent

 Definitive Inclusion Criteria:

 8. 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 ≤ 7 mm

 Then after the TR severity grading; the Clinical eligibility Committee will valid the
 inclusion.

 Non Inclusion Criteria:

 1. Patient treated with Mitraclip or other percutaneous approach on the mitral valve in
 the past 3-month

 2. Any prior tricuspid valve procedure that would interfere with placement of the Triclip
 device

 3. 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 (> 2cm) 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

 4. Myocardial infarction or coronary bypass surgery in the past 3-month

 5. Left ventricular ejection fraction ≤20%

 6. Cardiac Resynchronization therapy for less than 3-month and patients having a TR that
 is clearly related to the right ventricular lead positioning

 7. Cardioversion for less than 6 weeks

 8. Life expectancy irrespective of the valvular heart disease <1 year (due to
 co-morbidities)

 9. Other scheduled cardiac surgery (including registration in cardiac transplant list)

 10. Coronary angioplasty in the preceding month

 11. Current infection requiring prescription of antibiotics

 12. End-stage renal failure (dialysis patient)

 13. Severe hepatic insufficiency (disruption of liver metabolism associated with
 coagulation disorders (factor V <50%))

 14. Stroke in the previous 3-month

 15. Uncontrolled pre- capillary pulmonary hypertension (right catheterization required)
 (systolic pulmonary pressure > 60 mmHg)

 16. Mechanical prosthetic valve

 17. Pace maker lead or ICD lead that would prevent appropriate placement of the Triclips

 18. Nitinol allergy

 19. Contraindication, allergy or hypersensibility to dual anti-platelet and anticoagulant
 therapy

 20. Ongoing infection requiring antibiotic therapy

 21. Evidence of intra vascular or intra cardiac thrombus

 22. Patient who are included in another research protocol

 23. Protected person (adults legally protected (under judicial protection, guardianship or
 supervision), person deprived of their liberty, pregnant woman, lactating woman and
 minor)

 24. Absence of coverage by a social security scheme