TRICuspid Intervention in Heart Failure Trial (TRICI-HF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure Attributable to Severe Tricuspid Regurgitation
• Intervention / Treatment: Device: Transcatheter tricuspid valve treatment (TTVT)

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joerg Hausleiter, MD; Phone Number: +4989440072361; Email: joerg.hausleiter@med.uni-muenchen.de
• Study Contact Backup: Name: Thomas Stocker, MD; Phone Number: +49894400712625; Email: thomas.stocker@med.uni-muenchen.de

Study Locations

• Germany
  • Bad Krozingen, Germany
    • Not yet recruiting
    • Herzzentrum Bad Krozingen
    • Contact: Thomas Comberg
  • Bad Oeynhausen, Germany
    • Not yet recruiting
    • Herz- und Diabeteszentrum Nordrhein-Westfalen
    • Contact: Volker Rudolph
  • Bad Rothenfelde, Germany
    • Not yet recruiting
    • Schüchtermann-Klinik
    • Contact: Marek Kowalski
  • Berlin, Germany
    • Not yet recruiting
    • Deutsches Herzzentrum Berlin
    • Contact: Volkmar Falk
  • Berlin, Germany
    • Not yet recruiting
    • Charité Universitätsmedizin Berlin
    • Contact: Ulf Landmesser
  • Bonn, Germany
    • Not yet recruiting
    • Universitätsklinikum Bonn
    • Contact: Georg Nickenig
  • Dortmund, Germany
    • Not yet recruiting
    • St.-Johannes-Hospital Dortmund
    • Contact: Helge Möllmann
  • Erfurt, Germany
    • Not yet recruiting
    • Helios Klinikum Erfurt
    • Contact: Alexander Lauten
  • Essen, Germany
    • Not yet recruiting
    • Universitätsklinikum Essen
    • Contact: Tienush Rassaf
  • Frankfurt, Germany
    • Not yet recruiting
    • Universitatsklinikum Frankfurt
    • Contact: Andreas Zeiher
  • Freiburg, Germany
    • Not yet recruiting
    • Universitätsklinikum Freiburg
    • Contact: Christoph Bode
  • Giessen, Germany
    • Not yet recruiting
    • Universitätsklinikum Gießen
    • Contact: Holger Nef
  • Göttingen, Germany
    • Not yet recruiting
    • Herzzentrum Gottingen
    • Contact: Claudius Jacobshagen
  • Hamburg, Germany
    • Not yet recruiting
    • Herzzentrum UKE
    • Contact: Niklas Schofer, MD; Email: n.schofer@uke.de
  • Hamburg, Germany
    • Recruiting
    • Katholisches Marienkrankenhaus Hamburg
    • Contact: Elke Lubos, MD; Email: e.lubos@marienkrankenhaus.org
  • Hamburg, Germany
    • Recruiting
    • MVZ Prof. Mathey/Schofer
    • Contact: Joachim Schofer
  • Jena, Germany
    • Not yet recruiting
    • Universitätsklinikum Jena
    • Contact: Christian Schulze
  • Kiel, Germany
    • Recruiting
    • Universitätsklinikum Schleswig-Holstein
    • Contact: Derk Frank
  • Köln, Germany
    • Not yet recruiting
    • Herzzentrum Uniklinik Köln
  • Leipzig, Germany
    • Not yet recruiting
    • Herzentrum Leipzig
  • Mainz, Germany
    • Not yet recruiting
    • Universitätsmedizin Mainz
  • München, Germany
    • Recruiting
    • LMU Klinikum
    • Principal Investigator: Joerg Hausleiter, MD
    • Contact: Joerg Hausleiter, MD
    • Principal Investigator: Thomas Stocker, MD
    • Principal Investigator: Daniel Braun, MD
    • Principal Investigator: Steffen Massberg
  • Siegburg, Germany
    • Not yet recruiting
    • Herzzentrum Siegburg
    • Contact: Peter Boekstegers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental intervention; Transcatheter tricuspid valve treatment (TTVT) plus optimal medical therapy (OMT)	Device: Transcatheter tricuspid valve treatment (TTVT); 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).
No Intervention: Control intervention; OMT for severe tricuspid regurgitation in right-sided heart failure

What is the study measuring?

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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of transcatheter tricuspid valve intervention	Major adverse events that are related to the intervention and are relevant for patients undergoing TTVT: Mortality, life threatening bleeding (defined as BARC bleeding type 3 and 5), major vascular or cardiac structural complications requiring intervention, or mechanical circulatory support.	1 month

Collaborators and Investigators

• Sponsor: LMU Klinikum
• Collaborators: University of Leipzig; Heart Center Leipzig - University Hospital; Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK); Heart and Diabetes Center North Rhine-Westphalia; University Medical Center Mainz

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2022
• Primary Completion (Anticipated): March 1, 2026
• Study Completion (Anticipated): March 1, 2027

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): August 23, 2022
• Last Update Submitted That Met QC Criteria: August 19, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Heart Failure; Tricuspid Valve Insufficiency
• Other Study ID Numbers: TRICI-HF; TRICI-HF-DZHK24 (Other Grant/Funding Number: Deutsches Zentrum für Herzkreislaufforschung)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No