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

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ClinicalTrials.gov Identifier: NCT04646811
Recruitment Status : Not yet recruiting
First Posted : November 30, 2020
Last Update Posted : February 2, 2021
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital

Study Description
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Brief 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.


Condition or disease Intervention/treatment Phase
Tricuspid Regurgitation Procedure: Tricuspid valve Other: Best medical treatment Not Applicable

Detailed 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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : February 2021
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : July 2027
Arms and Interventions
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Arm Intervention/treatment
Experimental: Tricuspid valve
tricuspid valve percutaneous repair strategy with clip for the tricuspid valve
 Procedure: Tricuspid valve
Clip for the tricuspid valve implantation on top of best medical therapy
Best medical treatment Other: Best medical treatment
Best medical therapy alone


Outcome Measures
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Primary Outcome Measures :
  1. Milton Packer clinical composite score [ Time Frame: 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


Secondary Outcome Measures :
  1. number of participants with all-cause mortality [ Time Frame: 12 months ]
  2. number of participants with tricuspid valve surgery [ Time Frame: 12 months ]
  3. rate of heart failure hospitalizations [ Time Frame: 12 months ]
  4. assessment of quality of life improvement [ Time Frame: 0 and 12 months ]
    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.

  5. quality of life score [ Time Frame: 6 and 12 months ]
    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. quality of life score [ Time Frame: 6 and 12 months ]
    Minnesota Living with Heart Failure (MLHF)

  7. quality of life score [ Time Frame: 6 and 12 months ]

    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'.


  8. quality of life score [ Time Frame: 6 and 12 months ]
    Patient global assessment (PGA)

  9. functional evaluation [ Time Frame: 6 and 12 months ]
    NYHA functional class

  10. severity of the Tricuspid Regurgitation (TR) [ Time Frame: 6 and 12 months ]
    TR grade

  11. walking distance [ Time Frame: 6 and 12 months ]
    6-minute walk test

  12. echocardiography parameters [ Time Frame: 6 and 12 months ]
    right heart function

  13. echocardiography parameters [ Time Frame: 6 and 12 months ]
    right heart cavities sizes

  14. echocardiography parameters [ Time Frame: 6 and 12 months ]
    degree of tricuspid regurgitation

  15. echocardiography parameters [ Time Frame: 6 and 12 months ]
    stenosis

  16. biological parameters [ Time Frame: 6 and 12 months ]
    parameters renal : creatinine, clearance, AST

  17. biological parameters [ Time Frame: 6 and 12 months ]
    hepatic function

  18. biological parameters [ Time Frame: 6 and 12 months ]
    NT-proBNP

  19. overall survival [ Time Frame: 6 and 12 months ]
  20. number of cardiovascular death [ Time Frame: 6 and 12 months ]
  21. number of major cardiovascular events [ Time Frame: 6 and 12 months ]
  22. Incremental Cost-Effectiveness Ratio expressed as cost per QALY [ Time Frame: 12 and 24 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 ≤ 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04646811


Contacts
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Contact: Mevel Nicolas 02 99 28 25 55 dri@chu-rennes.fr
Contact: Ganivet Anne 02 99 28 25 55 anne.ganivet@chu-rennes.fr

Locations
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Sponsors and Collaborators
Rennes University Hospital
Investigators
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Principal Investigator: Donal Erwan CHU Rennes
More Information
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Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT04646811    
Other Study ID Numbers: 35RC18_8851_TRI-FR
2020-A00645-34 ( Other Identifier: N° IDRCB )
First Posted: November 30, 2020    Key Record Dates
Last Update Posted: February 2, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rennes University Hospital:
secondary Tricuspid Regurgitation
least severe Tricuspid Regurgitation
symptomatic patients
Additional relevant MeSH terms:
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Tricuspid Valve Insufficiency
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases