PMID- 34525259
OWN - NLM
STAT- MEDLINE
DCOM- 20220519
LR  - 20230509
IS  - 1527-6473 (Electronic)
IS  - 1527-6465 (Print)
IS  - 1527-6465 (Linking)
VI  - 28
IP  - 6
DP  - 2022 Jun
TI  - Early Everolimus-Facilitated Reduced Tacrolimus in Liver Transplantation: Results 
      From the Randomized HEPHAISTOS Trial.
PG  - 998-1010
LID - 10.1002/lt.26298 [doi]
AB  - 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(2) , difference: 4.1 mL/minute/1.73 m(2) ; P = 0.097). A significant difference 
      of 8.3 mL/minute/1.73 m(2) (P = 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.
CI  - (c) 2021 The Authors. Liver Transplantation published by Wiley Periodicals LLC on 
      behalf of American Association for the Study of Liver Diseases.
FAU - Nashan, Bjorn
AU  - Nashan B
AD  - Department of Hepatobiliary Surgery and Visceral Transplantation University 
      Medical Center Hamburg-Eppendorf Hamburg Germany Department of General, Visceral 
      and Transplant Surgery University Hospital Heidelberg Heidelberg Germany 
      Department of General, Visceral, Thoracic, Transplant and Pediatric Surgery 
      University Medical Center Schleswig-Holstein Kiel Germany Department of Surgery 
      University Hospital Regensburg Regensburg Germany Department of General, Visceral 
      and Transplant Surgery Charite-Universitatsmedizin Berlin Berlin Germany 
      Department of General, Visceral and Transplantation Surgery University Hospital 
      Essen Essen Germany Department of General, Visceral and Transplant Surgery 
      University Hospital Aachen Aachen Germany Novartis Pharma GmbH Nurnberg Germany 
      Organ Transplantation Center The First Affiliated Hospital of University of 
      Science and Technology of ChinaAnhui Provincial Hospital Hefei China General, 
      Visceral and Transplant SurgeryDepartment of Surgery Medical University of Graz 
      Graz Austria Department of General, Visceral and Transplantation Surgery 
      University Hospital Munster Munster Germany Department of GeneralVisceral and 
      Transplant Surgery University Hospital Aachen Aachen Germany Department of 
      General Surgery Maastricht University Medical Centre (MUMC) Maastricht the 
      Netherlands.
FAU - Schemmer, Peter
AU  - Schemmer P
FAU - Braun, Felix
AU  - Braun F
FAU - Schlitt, Hans J
AU  - Schlitt HJ
FAU - Pascher, Andreas
AU  - Pascher A
FAU - Klein, Christian G
AU  - Klein CG
FAU - Neumann, Ulf P
AU  - Neumann UP
FAU - Kroeger, Irena
AU  - Kroeger I
FAU - Wimmer, Peter
AU  - Wimmer P
CN  - Hephaistos Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT01551212
SI  - EudraCT/2011-003118-17
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20211012
PL  - United States
TA  - Liver Transpl
JT  - Liver transplantation : official publication of the American Association for the 
      Study of Liver Diseases and the International Liver Transplantation Society
JID - 100909185
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
CIN - Liver Transpl. 2022 Jun;28(6):925-927. PMID: 35124886
MH  - Everolimus/adverse effects
MH  - Glomerular Filtration Rate
MH  - Graft Rejection/epidemiology/etiology/prevention & control
MH  - Graft Survival
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects
MH  - *Liver Transplantation/adverse effects
MH  - *Tacrolimus/adverse effects
PMC - PMC9291476
EDAT- 2021/09/16 06:00
MHDA- 2022/05/20 06:00
PMCR- 2022/07/18
CRDT- 2021/09/15 17:28
PHST- 2021/08/05 00:00 [revised]
PHST- 2021/04/20 00:00 [received]
PHST- 2021/09/08 00:00 [accepted]
PHST- 2021/09/16 06:00 [pubmed]
PHST- 2022/05/20 06:00 [medline]
PHST- 2021/09/15 17:28 [entrez]
PHST- 2022/07/18 00:00 [pmc-release]
AID - 01445473-202206000-00017 [pii]
AID - LT26298 [pii]
AID - 10.1002/lt.26298 [doi]
PST - ppublish
SO  - Liver Transpl. 2022 Jun;28(6):998-1010. doi: 10.1002/lt.26298. Epub 2021 Oct 12.