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)
Stumpf J, Budde K, Witzke O, Sommerer C, Vogel T, Schenker P, Woitas RP, Opgenoorth M, Trips E, Schrezenmeier E, Hugo C, Girndt M, Wolf G, Kurschat C, Lopau K, Lutz J (2024)
Publication Type: Journal article
Publication year: 2024
Journal
Book Volume: 67
Article Number: 102381
DOI: 10.1016/j.eclinm.2023.102381
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.
Involved external institutions
Universitätsklinikum Carl Gustav Carus Dresden
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Universitätsklinikum Heidelberg
Germany (DE)
Universitätsklinikum Münster
Germany (DE)
Universitätsklinikum Knappschaftskrankenhaus Bochum
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Universitätsklinikum Heidelberg
Germany (DE)
Universitätsklinikum Münster
Germany (DE)
Universitätsklinikum Knappschaftskrankenhaus Bochum
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
How to cite
APA:
Stumpf, J., Budde, K., Witzke, O., Sommerer, C., Vogel, T., Schenker, P.,... Lutz, J. (2024). 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). EClinicalMedicine, 67. https://dx.doi.org/10.1016/j.eclinm.2023.102381
MLA:
Stumpf, Julian, et al. "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)." EClinicalMedicine 67 (2024).
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