Evaluation of Tricuspid Valve Percutaneous Repair System in the Treatment of Severe Secondary Tricuspid Disorders

Tricuspid Regurgitation Clinical Trial

— TRI-FR  

Official title:

TRI-FR : Multicentric Randomized Evaluation of Tricuspid Valve Percutaneous Repair System (Clip for the Tricuspid Valve) in the Treatment of Severe Secondary Tricuspid Disorders

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04646811
• Other study ID #: 35RC18_8851_TRI-FR
• Secondary ID: 2020-A00645-34
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 10, 2021
• Est. completion date: March 2024

Study information

• Verified date: May 2023
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Tricuspid Regurgitation
• Tricuspid Valve Insufficiency

Intervention

Procedure:
• Tricuspid valve
Clip for the tricuspid valve implantation on top of best medical therapy

Other:
• Best medical treatment
Best medical therapy alone

Locations

Country	Name	City	State
Belgium	Service de Cardiologie AZ Sint-Jan	Brugge
Belgium	Universitair Ziekenhuis Brussel	Bruxelles
Belgium	CHU Liège	Liège
France	CHU Amiens	Amiens
France	CHU Angers	Angers
France	CHU Bordeaux - Hôpital Cardiologique du Haut-Lévêque	Bordeaux
France	Centre Chirurgical Marie Lannelongue	Le Plessis-Robinson
France	CHU Lille	Lille
France	Hôpital Privé Le Bois	Lille
France	Hospices Civils de Lyon Groupement Hospitalier EST	Lyon
France	APHM - Hôpital La Timone	Marseille
France	Hôpital de Saint-Joseph	Marseille
France	Institut Cardiovasculaire Paris Sud Hôpital Jacques Cartier	Massy
France	Clinique du Millénaire	Montpellier
France	CHU Nantes - Hôtel Dieu et Hôpital Nord Laennec	Nantes
France	Hôpital Bichat	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Institut Mutualiste Montsouris	Paris
France	CHU Rennes - Hôpital Pontchaillou	Rennes
France	Centre Cardiologique du Nord	Saint-Denis
France	CHU La Réunion	Saint-Denis
France	CHU Saint-Etienne	Saint-Étienne
France	CHU Toulouse - Hôpital Rangueil	Toulouse
France	Clinique Pasteur	Toulouse
France	CHU Tours - Hôpital Trousseau	Tours
France	Médipôle Lyon-Villeurbanne	Villeurbanne

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Milton Packer clinical composite score	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	12 months
Secondary	number of participants with all-cause mortality		12 months
Secondary	number of participants with tricuspid valve surgery		12 months
Secondary	rate of heart failure hospitalizations		12 months
Secondary	assessment of quality of life improvement	Kansas City Cardiomyopathy Questionnaire score (KCCQ) The responses are categorized under 3 subscales (symptom burden, physical limitation and quality of life) with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The total KCCQ score represents the mean of the three subscale scores.	0 and 12 months
Secondary	quality of life score	Kansas City Cardiomyopathy Questionnaire (KCCQ) The responses are categorized under 3 subscales (symptom burden, physical limitation and quality of life) with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The total KCCQ score represents the mean of the three subscale scores.	6 and 12 months
Secondary	quality of life score	Minnesota Living with Heart Failure (MLHF)	6 and 12 months
Secondary	quality of life score	EQ5D-5L The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).; The descriptive system : 5 dimensions : mobility, self-care, usual activities, pain/discomfort, anxiety/depression.; 5 levels : no problems,slight problems, moderate, problems and extreme. Each level corresponds to 1 digit number. The digits for the 5 dimensions are combined into a 5-digit number.; The EQ VAS : on a vertical visual analogue scale, 100 'The best health you can imagine' 0 'The worst health you can imagine'.	6 and 12 months
Secondary	quality of life score	Patient global assessment (PGA)	6 and 12 months
Secondary	functional evaluation	NYHA functional class	6 and 12 months
Secondary	severity of the Tricuspid Regurgitation (TR)	TR grade	6 and 12 months
Secondary	walking distance	6-minute walk test	6 and 12 months
Secondary	echocardiography parameters	right heart function	6 and 12 months
Secondary	echocardiography parameters	right heart cavities sizes	6 and 12 months
Secondary	echocardiography parameters	degree of tricuspid regurgitation	6 and 12 months
Secondary	echocardiography parameters	stenosis	6 and 12 months
Secondary	biological parameters	parameters renal : creatinine, clearance, AST	6 and 12 months
Secondary	biological parameters	hepatic function	6 and 12 months
Secondary	biological parameters	NT-proBNP	6 and 12 months
Secondary	overall survival		6 and 12 months
Secondary	number of cardiovascular death		6 and 12 months
Secondary	number of major cardiovascular events		6 and 12 months
Secondary	Incremental Cost-Effectiveness Ratio expressed as cost per QALY		12 and 24 months