A comparative, randomized trial of concentration-controlled sirolimus combined with reduced-dose tacrolimus or standard-dose tacrolimus in renal allograft recipients

Transplant Proc. 2013 Jul-Aug;45(6):2133-40. doi: 10.1016/j.transproceed.2013.03.025.

Abstract

Background: The clinical safety and efficacy of sirolimus plus reduced-dose tacrolimus was evaluated in de novo renal allograft recipients enrolled in a comparative, open-label study.

Methods: One hundred twenty-eight renal allograft recipients were randomly assigned (1:1) to receive reduced-dose tacrolimus plus sirolimus (rTAC) or standard-dose tacrolimus and sirolimus (sTAC) for 6 months. The primary efficacy endpoint was calculated creatinine clearance values at 6 months.

Results: Demographic variables were similar between groups. At 6 months, mean (± standard deviation) calculated creatinine clearance was significantly improved in the rTAC group (63.8 vs 52.7 mL/min, P = .005), although mean serum creatinine values were not significantly different. Patient survival (95.2% and 96.9%) and graft survival (93.7% and 98.5%) were similar between the rTAC and sTAC groups, respectively. Acute rejection rates were 17.5% with rTAC and 7.7% with sTAC (P = .095).

Conclusions: The rTAC regimen provided effective immunosuppression and was associated with improved creatinine clearance. Adequate immunosuppressant exposure must be achieved in the early postoperative period to minimize the risk of acute rejection.

Publication types

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

MeSH terms

  • Adult
  • Biomarkers / blood
  • Creatinine / blood
  • Drug Monitoring
  • Drug Therapy, Combination
  • Europe
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacokinetics
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation* / adverse effects
  • Kidney Transplantation* / mortality
  • Male
  • Middle Aged
  • Prospective Studies
  • Sirolimus / administration & dosage*
  • Sirolimus / adverse effects
  • Sirolimus / pharmacokinetics
  • Tacrolimus / administration & dosage*
  • Tacrolimus / adverse effects
  • Tacrolimus / pharmacokinetics
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Immunosuppressive Agents
  • Creatinine
  • Sirolimus
  • Tacrolimus