6533b872fe1ef96bd12d4345

RESEARCH PRODUCT

Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial

P De SimoneFrederik NevensL De CarlisHj MetselaarS BeckebaumF SalibaS JonasD SudanJ FungL FischerC DuvouxKd ChavinB KoneruMa HuangWc ChapmanD FoltysS WitteH JiangJm HexhamG JungeFor The H2304 Study Group

subject

Graft RejectionCHRONIC KIDNEY-DISEASEMaleTime Factorsmedicine.medical_treatmentMedizinKaplan-Meier EstimateLiver transplantationKidneyKidney Function TestsGLOMERULAR-FILTRATION-RATEImmunosuppressive AgentHEPATOCELLULAR-CARCINOMASIROLIMUS-BASED IMMUNOSUPPRESSIONImmunology and AllergySirolimuPharmacology (medical)Prospective StudiestacrolimusMYCOPHENOLATE-MOFETILCOMPLICATIONSCross-Over Studiesliver transplantationwithdrawalGraft SurvivalCross-Over StudieMiddle AgedTreatment Outcomesurgical procedures operativeSurvival AnalysireducedLife Sciences & BiomedicineImmunosuppressive AgentsHumanGlomerular Filtration Ratemedicine.drugAdultmedicine.medical_specialtyRandomizationTime FactorAdolescentEfficacyUrologyRenal functionchemical and pharmacologic phenomenaCALCINEURIN INHIBITORRisk AssessmentDrug Administration ScheduleFollow-Up StudieYoung Adultstomatognathic systemTransplantation ImmunologyDOSE TACROLIMUSConfidence IntervalsmedicineHumansMETAANALYSISAgedSirolimusTransplantationKidney Function TestScience & TechnologyEverolimusDose-Response Relationship Drugbusiness.industryeverolimutacrolimuOriginal ArticleseverolimusSurvival AnalysisCrossover studyTacrolimusSurgeryTransplantationProspective StudieCONVERSIONstomatognathic diseasesSirolimusSurgerybusinessConfidence IntervalLiver FailureFollow-Up Studies

description

    In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (-3.0%; 95% CI -8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m(2) , 97.5% CI 3.74, 13.27 mL/min/1.73 m(2) , p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation. ispartof: American Journal of Transplantation vol:12 issue:11 pages:3008-3020 ispartof: location:United States status: published

yearjournalcountryeditionlanguage
2012-11-01American Journal of Transplantation
10.1111/j.1600-6143.2012.04212.xhttp://europepmc.org/articles/PMC3533764