Long-term follow-up of a phase III clinical trial comparing tacrolimus extended-release/MMF, tacrolimus/MMF, and cyclosporine/MMF in de novo kidney transplant recipients

Transplantation. 2014 Mar 27;97(6):636-41. doi: 10.1097/01.TP.0000437669.93963.8E.


Background: In a phase III, open-label, comparative, noninferiority study, 638 subjects receiving de novo kidney transplants were randomized to one of three treatment arms: tacrolimus extended-release (Astagraf XL) qd, tacrolimus (Prograf) bid, or cyclosporine (CsA) bid. All subjects received basiliximab induction, mycophenolate mofetil, and corticosteroids. Safety and efficacy follow-up data through 4 years are reported.

Methods: Evaluations included patient and graft survival, study drug discontinuations, laboratory values including renal function and development of new-onset diabetes after transplantation, concomitant medications, and adverse events.

Results: At study termination, 129 Astagraf XL, 113 Prograf, and 79 CsA patients had continued follow-up. Demographic and baseline characteristics were similar in all arms. Four-year Kaplan-Meier estimates of patient survival in the Astagraf XL, Prograf, and CsA groups were 93.2, 91.2, and 91.7%, respectively, while graft survival was 84.7, 82.7, and 83.9%, respectively. At least one serious adverse event was reported in the majority of patients in each group during the study (65.9% Astagraf XL, 69.8% Prograf, and 65.6% CsA). Renal function was not significantly different between Astagraf XL and Prograf. HgbA1c levels were collected every 6 months; the 4-year Kaplan-Meier estimate for incidence of HgbA1c levels ≥ 6.5% was significantly higher for both tacrolimus formulations compared to CsA; 41.1% (Astagraf XL), 33.6% (Prograf), and 21.3% (CsA).

Conclusions: In this 4-year follow-up report, patients receiving Astagraf XL and Prograf showed comparable efficacy and safety profiles, with a higher incidence of new-onset diabetes after transplantation but superior renal function compared to patients receiving CsA.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use*
  • Delayed-Action Preparations
  • Diabetes Mellitus / etiology
  • Drug Therapy, Combination
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / mortality
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Humans
  • Illinois
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Kidney / drug effects
  • Kidney / physiopathology
  • Kidney Transplantation* / adverse effects
  • Kidney Transplantation* / mortality
  • Male
  • Middle Aged
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Risk Factors
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Delayed-Action Preparations
  • Immunosuppressive Agents
  • Cyclosporine
  • Mycophenolic Acid
  • Tacrolimus