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Fixed low dose versus concentration-controlled initial tacrolimus dosing with reduced target levels in the course after kidney transplantation: results from a prospective randomized controlled non-inferiority trial (slow & low study)

Background - Optimal initial tacrolimus dosing and early exposure of tacrolimus after renal transplantation is not well studied. - Methods - In this open-label, 6 months, multicenter, randomized controlled, non-inferiority study, we randomly assigned 432 renal allograft recipients to receive basilix...

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Hauptverfasser: Stumpf, Julian David Christopher (VerfasserIn) , Budde, Klemens (VerfasserIn) , Witzke, Oliver (VerfasserIn) , Sommerer, Claudia (VerfasserIn) , Vogel, Thomas (VerfasserIn) , Schenker, Peter (VerfasserIn) , Woitas, Rainer Peter (VerfasserIn) , Opgenoorth, Mirian (VerfasserIn) , Trips, Evelyn (VerfasserIn) , Schrezenmeier, Eva (VerfasserIn) , Hugo, Christian (VerfasserIn) , Girndt, Matthias (VerfasserIn) , Wolf, Gunter (VerfasserIn) , Kurschat, Christine (VerfasserIn) , Lopau, Kai (VerfasserIn) , Lutz, Jens (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: January 2024
In: EClinicalMedicine
Year: 2024, Jahrgang: 67, Pages: 1-15
ISSN:2589-5370
DOI:10.1016/j.eclinm.2023.102381
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.eclinm.2023.102381
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2589537023005588
Volltext
Verfasserangaben:Julian Stumpf, Klemens Budde, Oliver Witzke, Claudia Sommerer, Thomas Vogel, Peter Schenker, Rainer Peter Woitas, Mirian Opgenoorth, Evelyn Trips, Eva Schrezenmeier, and Christian Hugo, German S&L Study
Beschreibung
Zusammenfassung:Background - Optimal initial tacrolimus dosing and early exposure of tacrolimus after renal transplantation is not well studied. - Methods - In this open-label, 6 months, multicenter, randomized controlled, non-inferiority study, we randomly assigned 432 renal allograft recipients to receive basiliximab induction, mycophenolate and steroids and either standard prolonged-release tacrolimus (trough levels: 7-9 ng/ml; Standard Care arm), or an initial 7-day fixed 5 mg/day dose of prolonged-release tacrolimus followed by lower tacrolimus predose levels (trough levels: 5-7 ng/ml; Slow & Low arm). The primary end point was the combined incidence rate of biopsy-proven acute rejections (BPAR; including borderline), graft failure, or death at 6 months with a non-inferiority margin of 12.5%. (EudraCT-Nr: 2013-001770-19. - Findings - The combined primary endpoint in the Slow & Low arm was non-inferior compared to the Standard Care arm (22.1% versus 20.7%; difference: 1.4%, 90% CI −5.5% to 8.3%). The overall rate of BPAR including borderlines was similar (Slow & Low 17.4% versus Standard Care 16.6%). Safety parameters such as delayed graft function, kidney function, donor specific HLA-antibodies, infections, or post-transplantation diabetes mellitus did not differ. - Interpretation - This is the first study to show that an initial fixed dose of 5 mg per day followed by lower tacrolimus exposure is non-inferior compared to standard tacrolimus therapy and equally efficient and safe within 6 months after renal transplantation. These data suggest that therapeutic drug monitoring for prolonged release tacrolimus can be abandoned until start of the second week after transplantation. - Funding - Investigator-initiated trial, financial support by Astellas Pharma GmbH.
Beschreibung:Online verfügbar: 22. Dezember 2023
Gesehen am 10.05.2024
Beschreibung:Online Resource
ISSN:2589-5370
DOI:10.1016/j.eclinm.2023.102381

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