## Protocol Section
### Identification Module
**NCT ID:** NCT05628779

**Acronym:** TRACE-NL

**Brief Title:** Evaluating Edge-to-edge Transcatheter Tricuspid Valve Repair in Patients With Severe Symptomatic Tricuspid Regurgitation

**Official Title:** Evaluation of the Safety, Efficacy and Cost-effectiveness of Transcatheter Tricuspid Valve Repair in Patients With Severe Tricuspid Regurgitation in the Netherlands.

#### Organization Study ID Info
**ID:** NL81645.100.22
#### Organization
**Class:** OTHER
**Full Name:** St. Antonius Hospital
### Status Module
#### Completion Date
**Date:** 2027-11-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-02-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-02-15

**Overall Status:** ENROLLING_BY_INVITATION

#### Primary Completion Date
**Date:** 2027-11-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-12-12

**Type:** ACTUAL

**Status Verified Date:** 2024-02

#### Study First Post Date
**Date:** 2022-11-29
**Type:** ACTUAL
**Study First Submit Date:** 2022-10-27
**Study First Submit QC Date:** 2022-11-16
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** ZonMw: The Netherlands Organisation for Health Research and Development

#### Lead Sponsor

**Class:** OTHER

**Name:** St. Antonius Hospital

#### Responsible Party

**Investigator Affiliation:** St. Antonius Hospital

**Investigator Full Name:** Martin J. Swaans

**Investigator Title:** Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** False

**Is US Export:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This is a national multicenter, open-label, randomized controlled trial to show superiority of edge-to-edge Transcatheter Tricuspid Valve repair (TTVr) on top of the Standard Of Care (SOC; heart failure medication) over the SOC alone in patients with symptomatic severe Tricuspid Regurgitation (TR) in the Netherlands.

**Detailed Description:** Tricuspid valve regurgitation (TR) is a common heart valve disease associated with mortality, heart failure hospitalization (HHF) and a significant negative impact on quality of life (QoL). The prevalence of moderate or severe TR in the Netherlands is estimated at 0.55% and becoming more prevalent. Surgery is rarely performed, because in-hospital mortality is high and there is little evidence for the efficacy. The majority of patients does therefore entirely dependent on treatment with heart failure medication. However, a subset of these patients experience (progressive) symptoms of refractory congestive heart failure despite the SOC with heart failure medication.

Transcatheter Tricuspid Valve repair (TTVr) offers several new strategies to address severe TR; one promising technique to treat patients with symptomatic severe TR is edge-to-edge tricuspid valve (TV) repair through leaflet approximation. Edge-to-edge TTVr may provide an elegant alternative treatment for many patients, because it is less burdensome due to the minimally invasive nature. Moreover, multiple single-arm trials already reported promising outcomes in terms of efficacy and safety, and the technique is very similar to Transcatheter Mitral Valve repair (TMVr), with yet proven feasibility, efficacy and safety.

The aim of this study is to evaluate the safety, efficacy and cost-effectiveness of TTVr for patients with symptomatic severe TR despite the SOC and high/prohibitive surgical risk in the Netherlands.

### Conditions Module

**Conditions:**

- Tricuspid Valve Regurgitation, Nonrheumatic

- Cardiac Catheterization

- Heart Failure, Right Sided

- Valve Regurgitation, Tricuspid

**Keywords:**

- Transcatheter tricuspid valve repair

- Tricuspid valve regurgitation

- Tricuspid valve

- Leaflet approximation devices

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** A total of 150 patients will be randomly assigned with a 2:1 allocation to either interventional (n=100) or control group (n=50).

##### Masking Info

**Masking:** NONE

**Masking Description:** Randomized controlled trial with open-label extension

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 150

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC)

**Intervention Names:**

- Device: TriClip TTVr system (Abbott Vascular)

- Device: PASCAL TTVr system (Edwards Lifesciences)

**Label:** Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC)

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Patients will continue the SOC with heart failure medication following the European Society of Cardiology guideline 2021 recommendations (e.g. diuretics)

**Label:** Standard Of Care (SOC)

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC)

**Description:** Edge-to-edge leaflet approximation for the tricuspid valve

**Name:** TriClip TTVr system (Abbott Vascular)

**Type:** DEVICE

#### Intervention 2

**Arm Group Labels:**

- Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC)

**Description:** Edge-to-edge leaflet approximation for the tricuspid valve

**Name:** PASCAL TTVr system (Edwards Lifesciences)

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** Quality of Life is measured with the Kansas City Cardiomyopathy Questionnaire with a 5 point change as clinically significant (0-100 points, higher score is better outcome)

**Measure:** Hierarchical composite of all-cause mortality, heart failure hospitalization and Quality of Life

**Time Frame:** 12 months

#### Secondary Outcomes

**Description:** Mortality of any cause

**Measure:** All-cause mortality

**Time Frame:** 12 months

**Description:** Hospitalization for acute decompensated heart failure

**Measure:** Hospitalization for heart failure

**Time Frame:** 12 months

**Description:** 5 point change is considered clinically significant (0-100 points with higher score is a better outcome), change of 5 points in Kansas City Cardiomyopathy Questionnaire is considered clinically meaningful

**Measure:** Change in Kansas City Cardiomyopathy Questionnaire

**Time Frame:** 12 months

**Description:** Cardiovascular mortality, myocardial infarction, stroke, major bleeding, device embolisation, new onset renal failure, endocarditis requiring surgery, non-elective cardiovascular surgery for device related adverse events.

**Measure:** Number of participants without Major Adverse Events (MAE)

**Time Frame:** 30 days and 12 months

**Description:** ranging from 0 to 4 (no limitation to severe limitation)

**Measure:** Change in New York Heart Association

**Time Frame:** 12 months

**Description:** Distance in meters (higher score is a better outcome)

**Measure:** Change in 6-Minute Walk Test

**Time Frame:** 12 months

**Description:** Echocardiographic assessment of Tricuspid Regurgitation (at least from severe to moderate or less)

**Measure:** Reduction tricuspid regurgitation

**Time Frame:** 30 days, 6 months and 12 months

**Description:** The investigators will compare the cost-effectiveness of the intervention group versus the control group based on lifetime horizon by constructing a Markov model with model parameters populated from the trial results as well as other published literature. The model will estimate the incremental cost-effectiveness ratio between the two groups

**Measure:** Cost-effectiveness as assessed by the Markov model

**Time Frame:** 12 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. The patient is symptomatic (New York Heart Association Functional Class II, III or ambulatory class IV) despite Standard Of Care (SOC). The Central Screening Committee (CSC) will assess whether the patient is receiving SOC. The CSC will also ensure that in case of the presence of atrial fibrillation, left sided heart valve disease (not requiring intervention) or coronary artery disease, conditions are first treated adequately with medication and/or (surgical) intervention.
2. The patient suffers from ≥ grade 3 isolated TR as determined by the assessment of a qualifying transthoracic echocardiogram (TTE) and three-dimensional transesophageal echocardiogram (3DTEE) and confirmed by the CSC, according to European Association for Percutaneous Cardiovascular Interventions (Tricuspid Focus Group) consensus document (in press). Note: If cardiac procedure(s) occur after eligibility was determined, TR grade will be re-assessed 30 days after the procedure.
3. The cardiac surgeon of the sites' local heart team concurs that the patient is at high estimated risk for mortality or morbidity with TV surgery.
4. The patient is ≥18 years of age at time of consent.
5. The patient must provide written informed consent prior to any trial related procedure.

Exclusion Criteria:

1. Systolic pulmonary artery pressure (sPAP) \> 70 mmHg or fixed pre-capillary pulmonary hypertension as assessed by right heart catheterization. Severe uncontrolled hypertension Systolic Blood Pressure (SBP) ≥ 180 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 110 mmHg.
2. Any condition that would interfere with a TTVr procedure, such as prior tricuspid valve repair or tricuspid valve leaflet anatomy which may preclude device implantation (e.g. calcification in grasping area, a severe coaptation defect of the tricuspid leaflets (no clip placement possible), pacemaker or Implantable Cardioverter Defibrillator (ICD) leads that would prevent appropriate placement or visualization of TTVr devices, Ebstein Anomaly (normal annulus position, but valve leaflets attached to walls and septum of the right ventricle), tricuspid valve anatomy non evaluable by echo, known allergy or hypersensitivity to dual antiplatelet therapy AND anticoagulant therapy or to device materials, femoral venous mass or thrombus or vegetation.
3. Indication for left-sided (e.g. severe aortic stenosis, severe mitral regurgitation) or pulmonary valve correction within prior 60 days. Note: concomitant mitral valve disease (e.g. mitral regurgitation) will be treated first and patients will be reassessed for the trial after 60 days.
4. Tricuspid valve stenosis - Defined as a tricuspid valve orifice of ≤ 1.0 cm2 and/or mean gradient ≥5 mmHg.
5. Left Ventricular Ejection Fraction (LVEF) ≤20%
6. Active endocarditis, active rheumatic heart disease, other ongoing infection requiring antibiotic therapy (enrolment possible 30 days after discontinuation of antibiotics with no active infection) or leaflets degenerated from rheumatic disease (i.e. noncompliant, perforated)
7. Myocardial infarction known unstable angina, or percutaneous coronary intervention within prior 30 days.
8. Hemodynamic instability defined as systemic systolic pressure \<90 mmHg with or without afterload reduction, cardiogenic shock or the need for inotropic support or hemodynamic support device (e.g. intra-aortic balloon pump).
9. Cerebrovascular Accident (CVA) within prior 90 days
10. Chronic dialysis
11. Bleeding disorders or hypercoagulable state, inability to use dual antithrombotic therapy due to contraindication, allergy or hypersensitivity
12. Active peptic ulcer or active gastrointestinal (GI) bleeding
13. Life expectancy of less than 12 months
14. Subject currently participating in another clinical trial (not yet completed primary endpoint) or in another clinical investigation for valvular heart disease.
15. Pregnant or nursing patients or those who plan pregnancy during the course of the trial. Women of childbearing age are required to have a negative pregnancy test 7 days prior to baseline visit. Women of childbearing age should be instructed to use safe contraception or have a sterilized regular partner.
16. Presence of anatomic or comorbid conditions, or other medical, social or psychological conditions that, in the eye of the investigator, limits the subject's ability to participate in the clinical investigation or comply with follow-up requirements, or impact the scientific soundness of the investigation results.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Amsterdam

**Country:** Netherlands

**Facility:** Amsterdam UMC

**Location 2:**

**City:** Groningen

**Country:** Netherlands

**Facility:** UMC Groningen

**Location 3:**

**City:** Leiden

**Country:** Netherlands

**Facility:** Leiden UMC

**Location 4:**

**City:** Maastricht

**Country:** Netherlands

**Facility:** Maastricht UMC+

**Location 5:**

**City:** Nieuwegein

**Country:** Netherlands

**Facility:** St. Antonius Hospital Nieuwegein

**Location 6:**

**City:** Rotterdam

**Country:** Netherlands

**Facility:** Erasmus University Medical Center

#### Overall Officials

**Official 1:**

**Affiliation:** St. Antonius Hospital

**Name:** M.J. Swaans, MD,PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Access Criteria:** These criteria will be made in consultation with the legal advisor of our institution and have not yet been drafted.

Specific degrees in the field of research have to be demonstrated, as wel as links with hospitals or research institutes of the researcher/physician (e.g. an employee contract)

**Description:** At the end of the study, the data will be locally saved at the st. Antonius Hospital and can be made available at request for reuse in other studies.

**Info Types:**

- STUDY_PROTOCOL

- SAP

**IPD Sharing:** YES

**Time Frame:** After publishing the main study articles, raw and modified data can be made available at request

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000006349

- Term: Heart Valve Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M9421

- Name: Heart Failure

- Relevance: HIGH

- As Found: Heart Failure, Right-Sided

- ID: M17014

- Name: Tricuspid Valve Insufficiency

- Relevance: HIGH

- As Found: Tricuspid Valve Regurgitation

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9437

- Name: Heart Valve Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006333

- Term: Heart Failure

- ID: D000014262

- Term: Tricuspid Valve Insufficiency

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M7411

- Name: Diuretics

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
