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Evaluation of Tricuspid Valve Percutaneous Repair System in the Treatment of Severe Secondary Tricuspid Disorders (TRI-FR)

R

Rennes University Hospital

Status

Completed

Conditions

Tricuspid Regurgitation

Treatments

Other: Best medical treatment
Procedure: Tricuspid valve

Study type

Interventional

Funder types

Other

Identifiers

NCT04646811
35RC18_8851_TRI-FR
2020-A00645-34 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

300 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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 ≤ 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:

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

  5. Left ventricular ejection fraction ≤35%

  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. Tricuspid 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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

300 participants in 2 patient groups

Tricuspid valve
Experimental group
Description:
tricuspid valve percutaneous repair strategy with clip for the tricuspid valve
Treatment:
Procedure: Tricuspid valve
Best medical treatment
Other group
Treatment:
Other: Best medical treatment

Trial contacts and locations

26

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Data sourced from clinicaltrials.gov

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