Early Everolimus‐Facilitated Reduced Tacrolimus in Liver Transplantation: Results From the Randomized HEPHAISTOS Trial
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- Björn Nashan
- Department of Hepatobiliary Surgery and Visceral Transplantation,University Medical Center Hamburg‐Eppendorf,Hamburg,Germany
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- Peter Schemmer
- Department of General, Visceral and Transplant Surgery,University Hospital Heidelberg,Heidelberg,Germany
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- Felix Braun
- Department of General, Visceral, Thoracic, Transplant and Pediatric Surgery,University Medical Center Schleswig‐Holstein,Kiel,Germany
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- Hans J. Schlitt
- Department of Surgery,University Hospital Regensburg,Regensburg,Germany
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- Andreas Pascher
- Department of General, Visceral and Transplant Surgery,Charité–Universitätsmedizin Berlin,Berlin,Germany
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- Christian G. Klein
- Department of General, Visceral and Transplantation Surgery,University Hospital Essen,Essen,Germany
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- Ulf P. Neumann
- Department of General, Visceral and Transplant Surgery,University Hospital Aachen,Aachen,Germany
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- Irena Kroeger
- Novartis Pharma GmbH,Nürnberg,Germany
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- Peter Wimmer
- Novartis Pharma GmbH,Nürnberg,Germany
抄録
<jats:p>Everolimus‐facilitated reduced‐exposure tacrolimus (EVR + rTAC) at 30 days after liver transplantation (LT) has shown advantages in renal preservation. This study evaluated the effects of early initiation of EVR + rTAC in de novo LT recipients (LTRs). In HEPHAISTOS (NCT01551212, EudraCT 2011‐003118‐17), a 12‐month, multicenter, controlled study, LTRs were randomly assigned at 7 to 21 days after LT to receive EVR + rTAC or standard‐exposure tacrolimus (sTAC) with steroids. The primary objective was to demonstrate superior renal function (assessed by estimated glomerular filtration rate [eGFR]) with EVR + rTAC versus sTAC at month 12 in the full analysis set (FAS). Other assessments at month 12 included the evaluation of renal function in compliance set and on‐treatment (OT) patients, efficacy (composite endpoint of graft loss, death, or treated biopsy‐proven acute rejection [tBPAR] and individual components) in FAS, and safety. In total, 333 patients (EVR + rTAC, 169; sTAC, 164) were included in the FAS. A high proportion of patients was nonadherent in maintaining tacrolimus trough levels (EVR + rTAC, 36.1%; sTAC, 34.7%). At month 12, the adjusted least square mean eGFR was numerically higher with EVR + rTAC versus sTAC (76.2 versus 72.1 mL/minute/1.73 m<jats:sup>2</jats:sup>, difference: 4.1 mL/minute/1.73 m<jats:sup>2</jats:sup>; <jats:italic toggle="yes">P</jats:italic> = 0.097). A significant difference of 8.3 mL/minute/1.73 m<jats:sup>2</jats:sup> (<jats:italic toggle="yes">P</jats:italic> = 0.03) favoring EVR + rTAC was noted in the compliance set. Incidence of composite efficacy endpoint (7.7% versus 7.9%) and tBPAR (7.1% versus 5.5%) at month 12 as well as incidence of treatment‐emergent adverse events (AEs) and serious AEs were comparable between groups. A lower proportion of patients discontinued EVR + rTAC than sTAC treatment (27.2% versus 34.1%). Early use of everolimus in combination with rTAC showed comparable efficacy, safety, and well‐preserved renal function versus sTAC therapy at month 12. Of note, renal function was significantly enhanced in the compliance set.</jats:p>
収録刊行物
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- Liver Transplantation
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Liver Transplantation 28 (6), 998-1010, 2021-10-12
Ovid Technologies (Wolters Kluwer Health)
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詳細情報 詳細情報について
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- CRID
- 1360298761836017536
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- DOI
- 10.1002/lt.26298
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- ISSN
- 15276473
- 15276465
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- データソース種別
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- Crossref