Efficacy and Safety of Everolimus Plus Low-Dose Tacrolimus Versus Mycophenolate Mofetil Plus Standard-Dose Tacrolimus in De Novo Renal Transplant Recipients: 12-Month Data

Am J Transplant. 2017 May;17(5):1358-1369. doi: 10.1111/ajt.14090. Epub 2017 Jan 4.


In this 12-month, multicenter, randomized, open-label, noninferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low-dose tacrolimus (EVR+LTac) or mycophenolate mofetil plus standard-dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti-thymocyte globulin). Noninferiority of composite efficacy failure rate (treated biopsy-proven acute rejection [tBPAR]/graft loss/death/loss to follow-up) in EVR+LTac versus MMF+STac was missed by 1.4%, considering the noninferiority margin of 10% (24.6% vs. 20.4%; 4.2% [-3.0, 11.4]). Incidence of tBPAR (19.1% vs. 11.2%; p < 0.05) was significantly higher, while graft loss (1.3% vs. 3.9%; p < 0.05) and composite of graft loss/death/lost to follow-up (6.1% vs. 10.5%, p = 0.05) were significantly lower in EVR+LTac versus MMF+STac groups, respectively. Mean estimated glomerular filtration rate was similar between EVR+LTac and MMF+STac groups (63.1 [22.0] vs. 63.1 [19.5] mL/min/1.73 m2 ) and safety was comparable. In conclusion, EVR+LTac missed noninferiority versus MMF+STac based on the 10% noninferiority margin. Further studies evaluating optimal immunosuppression for improved efficacy will guide appropriate dosing and target levels of EVR and LTac in RTxRs.

Keywords: antiproliferative agent: mycophenolate mofetil (MMF); calcineurin inhibitor: tacrolimus; clinical research/practice; immunosuppressant; immunosuppressive regimens; kidney transplantation/nephrology; mechanistic target of rapamycin: everolimus; minimization/withdrawal.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Equivalence Trials as Topic
  • Everolimus / therapeutic use*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Survival / drug effects*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use*
  • Postoperative Complications
  • Prognosis
  • Risk Factors
  • Safety
  • Tacrolimus / therapeutic use*
  • Young Adult


  • Immunosuppressive Agents
  • Everolimus
  • Mycophenolic Acid
  • Tacrolimus