Once-daily prolonged-release tacrolimus (ADVAGRAF) versus twice-daily tacrolimus (PROGRAF) in liver transplantation

Am J Transplant. 2010 Oct;10(10):2313-23. doi: 10.1111/j.1600-6143.2010.03255.x. Epub 2010 Sep 14.

Abstract

The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval -7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Female
  • Graft Rejection
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Kidney Function Tests
  • Liver Transplantation / immunology
  • Liver Transplantation / methods*
  • Male
  • Middle Aged
  • Tacrolimus / administration & dosage*
  • Tacrolimus / adverse effects
  • Tacrolimus / blood
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Tacrolimus