TRICuspid Intervention in Heart Failure Trial

Study Overview
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Brief Summary
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Functional tricuspid regurgitation (TR) is a serious and progressive disease. Guidelines recommend surgical valve repair of severe TR in symptomatic patients. Despite its association with excess mortality and morbidity, TR has been relatively neglected and is severely undertreated. In particular this is because isolated tricuspid surgery remains associated with high mortality rates, and thus, patients with severe TR are often deemed inoperable due to severe co-morbidities and frailty. In recent years, percutaneous CE-mark approved techniques for transcatheter tricuspid valve treatment (TTVT) have emerged as alternatives to surgery. These include (I) transcatheter annuloplasty devices (Tricuspid Cardioband) and (II) transcatheter edge-to-edge repair (TriClip, PASCAL). Several non-randomized studies suggested improved functional outcomes after TTVT, however, to data there is no evidence from randomized controlled trials addressing the actual efficacy of TTVT. The TRICuspid Intervention in Heart Failure trial (TRICI-HF trial) will assess the concept that TTVT will translate into a reduced morbidity and mortality. Patients will be randomly assigned in a 2:1 fashion to TTVT plus OMT (Experimental group) or OMT alone (Control group). TRICI-HF is an industry-independent, investigator-initiated strategy study and investigators may choose any suitable CE-marked percutaneous system on-label for TTVT.

Official Title
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TRICuspid Intervention in Heart Failure Trial (TRICI-HF-DZHK24)

Conditions
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Heart Failure Attributable to Severe Tricuspid Regurgitation

Intervention / Treatment
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* Device: Transcatheter tricuspid valve treatment (TTVT)


Participation Criteria
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Eligibility Criteria
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The following inclusion criteria were defined to assure generalizability of the population to be studied: Subject is symptomatic due to severe TR despite being on stable OMT for at least 30 days based on judgment of the local heart team. Patients with reduced left ventricular ejection fraction (HFrEF) will likely constitute a minority among eligible patients with isolated severe tricuspid regurgitation (9,13). However, HFrEF patients enrolled into the trial need to be on stable guideline-directed medical therapy for at least 4 weeks.. Subject is at intermediate or greater estimated risk of mortality with tricuspid valve surgery based on judgment of the local heart team New York Heart Association (NYHA) Functional Class II, III or IVa Femoral vein access and valve anatomy are determined to be feasible for interventional treatment (including sufficient quality of TTE and TEE imaging) Age ≥ 18 years at time of consent Subject must provide written informed consent prior to any trial related procedure The following exclusion criteria were selected to define a representative study cohort: Presence of severe aortic, mitral or pulmonary valve disease OR surgical/interventional treatment at the aortic, mitral or pulmonary valves prior 60 days Right heart catheterization (mandatory) with systolic pulmonary artery pressure > 70 mmHg or substantial pre-capillary pulmonary hypertension (defined as mean pulmonary artery pressure (mPAP) >30 mmHg plus transpulmonary gradient (TPG) >17 mmHg or pulmonary vascular resistance (PVR) >5 wood units) Tricuspid valve stenosis (tricuspid mean gradient > 5 mmHg) Pacemaker or ICD leads that would prevent appropriate TTVT Prior tricuspid valve procedures or tricuspid valve leaflet anatomy that would interfere with appropriate TTVT (e.g. calcification, Ebstein anomaly, coaptation defect > 8mm for planned leaflet- and annuloplasty-based therapy) Chronic renal failure requiring dialysis Tricuspid valve anatomy not evaluable by TTE and TEE Myocardial infarction or cerebrovascular accident within prior 90 days Life expectancy of less than 12 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Prospective, controlled, multicenter, randomized, open label trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental intervention<br>Transcatheter tricuspid valve treatment (TTVT) plus optimal medical therapy (OMT) | Device: Transcatheter tricuspid valve treatment (TTVT)<br>* Percutaneous CE-mark approved techniques for transcatheter tricuspid valve treatment (TTVT): These include (I) transcatheter annuloplasty devices (Tricuspid Cardioband) and (II) transcatheter edge-to-edge repair (TriClip, PASCAL).<br>|
| No Intervention: Control intervention<br>OMT for severe tricuspid regurgitation in right-sided heart failure | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality or heart failure hospitalization | Composite of time to all-cause mortality or heart failure hospitalization - whichever occurs first - at a minimum follow-up of 12 months | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality (unadjusted and adjusted for TR severity at baseline) |  | 12 months | 
| Heart failure hospitalizations (frequency and length; unadjusted and adjusted for TR severity at baseline) |  | 12 months | 
| Change in Quality of Life as assessed by the MLHFQ from baseline |  | 12 months | 
| Re-intervention rates for recurrent tricuspid regurgitation |  | 12 months | 
| Change in NYHA Class from baseline (≥III/IV to ≤I/II) |  | 12 months | 
| Change in 6 minute walk test distance from baseline |  | 12 months | 
| Change in echocardiographic parameters (among others: TR grade I-V, RV dimension and function, LV dimension and function, estimation of sPAP) |  | 12 months | 
| Development of tricuspid stenosis (mean inflow gradient >5mmHg) |  | 12 months | 
| Change in peripheral edema assessed by the edema scale (grade I-IV) and subject weight (kilograms) from baseline |  | 12 months | 
| Change of diuretic drugs and heart failure medications from baseline (type and dosage) |  | 12 months | 
| Change in laboratory markers for cardiac, renal and hepatic function (complete blood count, NT-proBNP, eGFR, serum creatinine, bilirubin, AST, ALT and gGT) |  | 12 months |