Fixed low dose versus concentration-controlled initial tacrolimus dosing with reduced target levels in the course after kidney transplantation

• Verfasst von: Stumpf, Julian David Christopher [VerfasserIn]
• Verfasst von: Budde, Klemens [VerfasserIn]
• Verfasst von: Witzke, Oliver [VerfasserIn]
• Verfasst von: Sommerer, Claudia [VerfasserIn]
• Verfasst von: Vogel, Thomas [VerfasserIn]
• Verfasst von: Schenker, Peter [VerfasserIn]
• Verfasst von: Woitas, Rainer Peter [VerfasserIn]
• Verfasst von: Opgenoorth, Mirian [VerfasserIn]
• Verfasst von: Trips, Evelyn [VerfasserIn]
• Verfasst von: Schrezenmeier, Eva [VerfasserIn]
• Verfasst von: Hugo, Christian [VerfasserIn]
• Verfasst von: Girndt, Matthias [VerfasserIn]
• Verfasst von: Wolf, Gunter [VerfasserIn]
• Verfasst von: Kurschat, Christine [VerfasserIn]
• Verfasst von: Lopau, Kai [VerfasserIn]
• Verfasst von: Lutz, Jens [VerfasserIn]
• Titel: Fixed low dose versus concentration-controlled initial tacrolimus dosing with reduced target levels in the course after kidney transplantation
• Titelzusatz: results from a prospective randomized controlled non-inferiority trial (slow & low study)
• Verf.angabe: 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
• E-Jahr: 2024
• Jahr: January 2024
• Umfang: 15 S.
• Illustrationen: Illustrationen
• Fussnoten: Online verfügbar: 22. Dezember 2023 ; Gesehen am 10.05.2024
• Titel Quelle: Enthalten in: EClinicalMedicine
• Ort Quelle: Amsterdam : Elsevier, 2018
• Jahr Quelle: 2024
• Band/Heft Quelle: 67(2024) vom: Jan., Artikel-ID 102381, Seite 1-15
• ISSN Quelle: 2589-5370
• DOI: doi:10.1016/j.eclinm.2023.102381
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Fixed low dose
• Sach-SW: Immunosuppression
• Sach-SW: Renal transplantation
• Sach-SW: Tacrolimus monitoring
• K10plus-PPN: 1888238402

Abstract

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.