Cardiac Catheterization, Heart Failure, Right Sided, Tricuspid Valve Regurgitation, Nonrheumatic, Valve Regurgitation, Tricuspid
Conditions
Keywords
Transcatheter tricuspid valve repair, Tricuspid valve regurgitation, Tricuspid valve, Leaflet approximation devices
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.
Interventions
DEVICEPASCAL TTVr system (Edwards Lifesciences)
Edge-to-edge leaflet approximation for the tricuspid valve
DEVICETriClip TTVr system (Abbott Vascular)
Edge-to-edge leaflet approximation for the tricuspid valve
Sponsors
ZonMw: The Netherlands Organisation for Health Research and Development
St. Antonius Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Randomized controlled trial with open-label extension
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hierarchical composite of all-cause mortality, heart failure hospitalization and Quality of Life | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization for heart failure | 12 months | Hospitalization for acute decompensated heart failure |
| Change in Kansas City Cardiomyopathy Questionnaire | 12 months | 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 |
| Number of participants without Major Adverse Events (MAE) | 30 days and 12 months | 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. |
| All-cause mortality | 12 months | Mortality of any cause |
| Change in 6-Minute Walk Test | 12 months | Distance in meters (higher score is a better outcome) |
| Reduction tricuspid regurgitation | 30 days, 6 months and 12 months | Echocardiographic assessment of Tricuspid Regurgitation (at least from severe to moderate or less) |
| Cost-effectiveness as assessed by the Markov model | 12 months | 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 |
| Change in New York Heart Association | 12 months | ranging from 0 to 4 (no limitation to severe limitation) |
Countries
Netherlands
Outcome results
None listed