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)
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Beitragende
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.
Details
Originalsprache | Englisch |
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Aufsatznummer | 102381 |
Seiten (von - bis) | 1-15 |
Seitenumfang | 15 |
Fachzeitschrift | EClinicalMedicine |
Jahrgang | 67 |
Frühes Online-Datum | 22 Dez. 2023 |
Publikationsstatus | Veröffentlicht - Jan. 2024 |
Peer-Review-Status | Ja |
Externe IDs
PubMedCentral | PMC10751828 |
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Scopus | 85180608293 |
ORCID | /0000-0002-6530-5855/work/151983262 |
Mendeley | f9fd93a4-55e8-340b-ba05-64cbc496a377 |