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)Research in context
Summary: 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 b...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | EClinicalMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537023005588 |
| _version_ | 1827374967557193728 |
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| author | Julian Stumpf Klemens Budde Oliver Witzke Claudia Sommerer Thomas Vogel Peter Schenker Rainer Peter Woitas Mirian Opgenoorth Evelyn Trips Eva Schrezenmeier Christian Hugo Matthias Girndt Gunter Wolf Christine Kurschat Kai Lopau Jens Lutz |
| author_facet | Julian Stumpf Klemens Budde Oliver Witzke Claudia Sommerer Thomas Vogel Peter Schenker Rainer Peter Woitas Mirian Opgenoorth Evelyn Trips Eva Schrezenmeier Christian Hugo Matthias Girndt Gunter Wolf Christine Kurschat Kai Lopau Jens Lutz |
| author_sort | Julian Stumpf |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-08T11:42:57Z |
| format | Article |
| id | doaj.art-e718179a569e40baa1299dd11a9a5e74 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-03-08T11:42:57Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-e718179a569e40baa1299dd11a9a5e742024-01-25T05:23:32ZengElsevierEClinicalMedicine2589-53702024-01-0167102381Fixed 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)Research in contextJulian Stumpf0Klemens Budde1Oliver Witzke2Claudia Sommerer3Thomas Vogel4Peter Schenker5Rainer Peter Woitas6Mirian Opgenoorth7Evelyn Trips8Eva Schrezenmeier9Christian Hugo10Matthias GirndtGunter WolfChristine KurschatKai LopauJens LutzDivision of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, GermanyDepartment of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, GermanyDepartment of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, GermanyDepartment of Nephrology, Kidney Center, University Hospital Heidelberg, Heidelberg, GermanyDepartment of General, Visceral and Transplant Surgery, University Hospital Münster, Münster, GermanyDepartment of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, GermanyDepartment of Internal Medicine I, University of Bonn, Bonn, GermanyDepartment of Nephrology and Hypertension, University Hospital of Erlangen, Erlangen, GermanyCoordination Centre for Clinical Trials, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, Dresden, GermanyDepartment of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Academy, Clinician Scientist Program Universitätsmedizin Berlin, Berlin, GermanyDivision of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; Corresponding author. Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.Summary: 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.http://www.sciencedirect.com/science/article/pii/S2589537023005588Renal transplantationTacrolimus monitoringFixed low doseImmunosuppression |
| spellingShingle | Julian Stumpf Klemens Budde Oliver Witzke Claudia Sommerer Thomas Vogel Peter Schenker Rainer Peter Woitas Mirian Opgenoorth Evelyn Trips Eva Schrezenmeier Christian Hugo Matthias Girndt Gunter Wolf Christine Kurschat Kai Lopau Jens Lutz 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)Research in context EClinicalMedicine Renal transplantation Tacrolimus monitoring Fixed low dose Immunosuppression |
| title | 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)Research in context |
| title_full | 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)Research in context |
| title_fullStr | 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)Research in context |
| title_full_unstemmed | 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)Research in context |
| title_short | 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)Research in context |
| title_sort | 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 amp low study research in context |
| topic | Renal transplantation Tacrolimus monitoring Fixed low dose Immunosuppression |
| url | http://www.sciencedirect.com/science/article/pii/S2589537023005588 |
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