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Evaluation of the safety, efficacy and cost-effectiveness of transcatheter tricuspid valve repair in patients with severe tricuspid regurgitation in the Netherlands (TRACE-NL)

Projectomschrijving

Mensen met een ernstige lekkage van de tricuspidalisklep ervaren een slechte kwaliteit van leven en overlijden vaak vroegtijdig aan deze aandoening. Sinds kort is het mogelijk om de tricuspidalisklep te repareren via een katheter door een kleine toegang in de liesader. Met een studie hiernaar gaan we onderzoeken of deze nieuwe behandeling resulteert in een langere levensduur, minder hartfalen en een betere kwaliteit van leven.
De tricuspidalisklep is de hartklep tussen de rechterkamer en rechterboezem. Indien deze klep lekt, kunnen verschijnselen van hartfalen ontstaan, zoals vochtophoping en kortademigheid. Op dit moment is er nog niet voor iedereen een goede behandeling. Vochtafdrijvende medicijnen werken vaak onvoldoende, en een openhartoperatie om de hartklep te repareren, gaat gepaard met een hoog risico op overlijden.
De hoop is nu gevestigd op de transkatheter tricuspidalisklep-reparatie. Het St. Antonius Ziekenhuis ontvangt € 7,1 miljoen om de effectiviteit en kosteneffectiviteit van deze behandeling aan te tonen.

Meer informatie

Bekijk informatie over dit project op de website van Zorginstituut Nederland

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Samenvatting van de aanvraag

RESEARCH QUESTION / HYPOTHESIS The principal hypothesis is that for patients with a symptomatic severe tricuspid valve regurgitation (TR), treatment with a transcatheter repair system on top of optimal medical therapy (OMT) is superior to OMT alone for the prevention of death, heart failure hospitalizations and improvement in quality of life • STUDY POPULATION Patients with symptomatic severe isolated TR despite OMT and at high/prohibitive surgical risk • INTERVENTION Transcatheter tricuspid valve repair (TTVr) using a tissue approximation (edge-to-edge repair) technique on top of OMT. All edge-to-edge tricuspid valve repair systems are allowed in the study, as long as the device has CE-mark and has demonstrated sufficient safety and efficacy. • COMPARISON Optimal medical therapy • OUTCOMES The primary endpoint is defined as the hierarchical occurrence of all-cause death, hospitalizations related to heart failure, and the change in KCCQ (quality of life) at one year. Secondary outcome measures: - All cause mortality (1 year) - Hospitalization related to heart failure (1 year) - Change in KCCQ (1 year) - Freedom from major adverse events (30 days, 1 year) - Change in NYHA class (1 year) - Change in 6MWT (1 year) - TR-reduction from (at least) severe tot moderate or less (30 days, 6 months 1 year) - Learning curve - Cost-effectiveness • FOLLOW-UP TIME The primary outcome measure is determined at 12 months after randomization. All secondary endpoints are determined at 1 year too. Procedural results and early safety are also measured at 30 days. All clinical events that occur between 1-3 years after randomization will be recorded for descriptive purposes. • STUDY DESIGN 1. Pre-trial phase (learning curve, n=48): To obtain experience, all 6 participating centers will perform 8 TTVr procedures before including patients into the RCT. 2. To demonstrate the effectiveness of TTVr over OMT, we chose to perform a national multicenter open label superiority RCT (n=150) with a 2:1 inclusion rate favoring the device arm. • SAMPLE SIZE & DATA ANALYSIS The analysis of the primary endpoint will be performed with the use of a nonparametric pair-wise-comparison method previous described by Finkelstein and Schoenfeld and Pocock et al. This method is constructed as a comparative outcome assessment for all pairs of patients from the TTVr and OMT group, in terms of ‘favoring TTVr’ or ‘favoring OMT’. If a pair favors TTVr, it is considered a ‘win for TTVr’, and if it favors OMT, it is a ‘win for OMT’. In the pair-wise comparative outcomes assessment, the occurrence of death within one year has priority over the number of hospital admissions related to heart failure. If no event-based winner can be declared, the pair is compared with regard to the change in KCCQ at one year, and a difference of at least 5 points favors the corresponding treatment. A tie is declared if the difference between the two changes in KCCQ is less than 5 points. The statistical analysis then proceeds by statistically comparing the number of wins for TTVr with that for OMT, according to statistical methods described by Finkelstein and Schoenfeld, which are equivalent to the Win-Ratio approach proposed by Pocock et al. Patients with tricuspid regurgitation on OMT were previously described by Messika-Zeitoun et al, who reported an all-cause mortality rate of 17.8% per year and 22.2% hospitalization due to heart failure. The change in KCCQ in the control group is assumed to be 0 points (no change in therapy). From previously published data, we expect an all-cause mortality rate of 7.1% per year and a 15% hospitalization (40% reduction) due to heart failure in the TTVr arm. In this TRILUMINATE study, a 20 (SD 21) point increase in KCCQ is reported. Because of the hierarchical end point analysis using a win-ratio approach, the KCCQ score in this study is decisive only for patients who survived the follow up without hospital admission. The expected increase in quality of life/functional status for these patients is expected to be lower compared to the whole TTVr group, and assumed to be 12 (SD 21) points. A difference in KCCQ change of 5 points is considered clinically relevant. With 90 and 45 fully evaluable patients in the TTVr and control arm, the trial is provided with at least 80% power to show superiority of TTVr over usual care at a two-sided significance level of 5%. Allowing for a dropout rate of 10%, a sample size of 150 patients (100 patients in the TTVr arm and 50 in the control arm) is required. • COST-EFFECTIVENESS ANALYSIS / BUDGET IMPACT ANALYSIS The cost-effectiveness and budget impact analysis will be performed by a health technology assessment expert with extensive experience in setting up, conducting and analyzing trial based and model based economic evaluations in various clinical fields.

Onderwerpen

Kenmerken

Projectnummer:
2021038369
Looptijd: 32%
Looptijd: 32 %
2022
2028
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
dr. M.J. Swaans MD PhD
Verantwoordelijke organisatie:
St. Antonius Ziekenhuis