Tricuspid Valve Regurgitation, NonrheumaticTRACE-NLNCT05628779
Evaluating Edge-to-edge Transcatheter Tricuspid Valve Repair in Patients With Severe Symptomatic Tricuspid Regurgitation
A study testing TriClip TTVr system (Abbott Vascular) and PASCAL TTVr system (Edwards Lifesciences) in people with Tricuspid Valve Regurgitation, Nonrheumatic and Cardiac Catheterization, run by St. Antonius Hospital at 6 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tricuspid Valve Regurgitation, Nonrheumatic, Cardiac Catheterization, Heart Failure, Right Sided
- What is being tested?
- TriClip TTVr system (Abbott Vascular) and PASCAL TTVr system (Edwards Lifesciences)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 6 sitesNetherlands
- Study dates
- 12 Dec 2022to 1 Nov 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- 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.
- The patient is ≥18 years of age at time of consent.
- The patient must provide written informed consent prior to any trial related procedure.
Who cannot join
- 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.
- 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.
- 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.
- Tricuspid valve stenosis - Defined as a tricuspid valve orifice of ≤ 1.0 cm2 and/or mean gradient ≥5 mmHg.
- Left Ventricular Ejection Fraction (LVEF) ≤20%
- 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)
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- Myocardial infarction known unstable angina, or percutaneous coronary intervention within prior 30 days.
- 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).
- Cerebrovascular Accident (CVA) within prior 90 days
- Chronic dialysis
- Bleeding disorders or hypercoagulable state, inability to use dual antithrombotic therapy due to contraindication, allergy or hypersensitivity
- Active peptic ulcer or active gastrointestinal (GI) bleeding
- Life expectancy of less than 12 months
- Subject currently participating in another clinical trial (not yet completed primary endpoint) or in another clinical investigation for valvular heart disease.
- 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.
- 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.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Netherlands6 sites
Amsterdam UMC
Amsterdam
UMC Groningen
Groningen
Leiden UMC
Leiden
Maastricht UMC+
Maastricht
St. Antonius Hospital Nieuwegein
Nieuwegein
Erasmus University Medical Center
Rotterdam
About this study
Official title: Evaluation of the Safety, Efficacy and Cost-effectiveness of Transcatheter Tricuspid Valve Repair in Patients With Severe Tricuspid Regurgitation in the Netherlands.
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.
Read the 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
- Tricuspid Valve Regurgitation, Nonrheumatic, Cardiac Catheterization, Heart Failure, Right Sided, Valve Regurgitation, Tricuspid
- Being tested
- TriClip TTVr system (Abbott Vascular), PASCAL TTVr system (Edwards Lifesciences)
- Keywords
- Transcatheter tricuspid valve repair, Tricuspid valve regurgitation, Tricuspid valve, Leaflet approximation devices
- Medical subject headings
- Tricuspid Valve Insufficiency, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TriClip TTVr system (Abbott Vascular)Device
Edge-to-edge leaflet approximation for the tricuspid valve
PASCAL TTVr system (Edwards Lifesciences)Device
Edge-to-edge leaflet approximation for the tricuspid valve
| Study group | Role | What they receive |
|---|---|---|
| Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC) | Experimental | Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC) Receives: Device: TriClip TTVr system (Abbott Vascular); Device: PASCAL TTVr system (Edwards Lifesciences) |
| Standard Of Care (SOC) | No intervention | Patients will continue the SOC with heart failure medication following the European Society of Cardiology guideline 2021 recommendations (e.g. diuretics) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hierarchical composite of all-cause mortality, heart failure hospitalization and Quality of Life
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)
Measured: 12 months
Secondary outcomes (8)
All-cause mortality
Mortality of any cause
Measured: 12 months
Hospitalization for heart failure
Hospitalization for acute decompensated heart failure
Measured: 12 months
Change in Kansas City Cardiomyopathy Questionnaire
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
Measured: 12 months
Number of participants without Major Adverse Events (MAE)
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.
Measured: 30 days and 12 months
Change in New York Heart Association
ranging from 0 to 4 (no limitation to severe limitation)
Measured: 12 months
Change in 6-Minute Walk Test
Distance in meters (higher score is a better outcome)
Measured: 12 months
Reduction tricuspid regurgitation
Echocardiographic assessment of Tricuspid Regurgitation (at least from severe to moderate or less)
Measured: 30 days, 6 months and 12 months
Cost-effectiveness as assessed by the Markov model
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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2022
- Study start12 Dec 2022
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tricuspid Valve Regurgitation, NonrheumaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Antonius Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, Martin J. Swaans, St. Antonius Hospital
- Investigators
- M.J. Swaans, MD,PhD, Principal investigator, St. Antonius Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05628779
- Sponsor's protocol ID
- NL81645.100.22
- Acronym
- TRACE-NL
- Status last verified
- Feb 2024
- First submitted
- 27 Oct 2022
- Last updated
- 16 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Safety, Efficacy and Cost-effectiveness of Transcatheter Tricuspid Valve Repair in Patients With Severe Tricuspid Regurgitation in the Netherlands.
- ClinicalTrials.gov ID
- NCT05628779
- Acronym / sponsor ID
- TRACE-NL / NL81645.100.22
- 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
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- St. Antonius HospitalUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 12 Dec 2022 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Nov 2027 (estimated)
- First posted
- 29 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC) | Experimental | Device: TriClip TTVr system (Abbott Vascular), Device: PASCAL TTVr system (Edwards Lifesciences)Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC) |
| Standard Of Care (SOC) | No intervention | –Patients will continue the SOC with heart failure medication following the European Society of Cardiology guideline 2021 recommendations (e.g. diuretics) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
- 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.
- 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.
- The patient is ≥18 years of age at time of consent.
- The patient must provide written informed consent prior to any trial related procedure.
Key exclusion criteria (16 listed)
- 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.
- 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.
- 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.
- Tricuspid valve stenosis - Defined as a tricuspid valve orifice of ≤ 1.0 cm2 and/or mean gradient ≥5 mmHg.
- Left Ventricular Ejection Fraction (LVEF) ≤20%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TriClip TTVr system (Abbott Vascular)Edge-to-edge leaflet approximation for the tricuspid valve | Device | Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC) |
| PASCAL TTVr system (Edwards Lifesciences)Edge-to-edge leaflet approximation for the tricuspid valve | Device | Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC) |
Primary outcome
Hierarchical composite of all-cause mortality, heart failure hospitalization and Quality of Life
Time frame: 12 months
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)
8 secondary outcomes
All-cause mortality
Time frame: 12 months
Hospitalization for heart failure
Time frame: 12 months
Change in Kansas City Cardiomyopathy Questionnaire
Time frame: 12 months
Number of participants without Major Adverse Events (MAE)
Time frame: 30 days and 12 months
Change in New York Heart Association
Time frame: 12 months
Change in 6-Minute Walk Test
Time frame: 12 months
Reduction tricuspid regurgitation
Time frame: 30 days, 6 months and 12 months
Cost-effectiveness as assessed by the Markov model
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2024.
- Individual participant dataSharing planned: Yes. 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
M.J. Swaans, MD,PhD principal investigator
St. Antonius Hospital
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TriClip TTVr system (Abbott Vascular) and PASCAL TTVr system (Edwards Lifesciences) in people with Tricuspid Valve Regurgitation, Nonrheumatic and Cardiac Catheterization, run by St. Antonius Hospital at 6 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 16 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hierarchical composite of all-cause mortality, heart failure hospitalization and Quality of Life (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2024.