A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients

Transplantation. 2003 Mar 27;75(6):844-51. doi: 10.1097/01.TP.0000056635.59888.EF.


Background: Induction therapy with antithymocyte globulin (ATG) reduces the incidence of acute rejection after transplantation. A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients.

Methods: In a 6-month, open-label, randomized, prospective study conducted in 30 European centers, 555 renal transplant patients were randomly assigned to tacrolimus triple therapy (Tac triple, n=185), ATG induction with tacrolimus (ATG-Tac, n=186), or ATG induction with CsA microemulsion (ATG-CsA, n=184); all were combined with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy.

Results: Patient demographics and clinical parameters at baseline were similar. Patient and graft survival rates were similar in all groups. The incidence of clinically apparent acute rejection was significantly higher (P=0.003) for Tac triple (33.0%) compared with ATG-Tac (22.6%) and the incidence for ATG-Tac was significantly lower (P=0.004) than for ATG-CsA (37.0%). The incidences of acute rejection confirmed by biopsy (primary endpoint) were 25.4%, 15.1%, and 21.2% for Tac triple, ATG-Tac, and ATG-CsA, respectively (Tac triple vs. ATG-Tac, P=0.004). The incidences of corticosteroid-resistant acute rejection were 7.0% (Tac triple), 4.8% (ATG-Tac), and 10.9% (ATG-CsA) (ATG-Tac vs. ATG-CsA, P=0.038). In the ATG groups, the incidences of leukopenia, thrombocytopenia, serum sickness, fever, and cytomegalovirus infection were significantly higher (P<0.05).

Conclusions: Acute rejection was significantly lower in the ATG-Tac group compared with the ATG-CsA and Tac triple groups. Significantly more hematologic and infectious adverse events were observed in both ATG induction groups.

Publication types

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

MeSH terms

  • Acute Disease
  • Adult
  • Antilymphocyte Serum / administration & dosage*
  • Antilymphocyte Serum / adverse effects
  • Cyclosporine / administration & dosage*
  • Cyclosporine / adverse effects
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / mortality
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Incidence
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Patient Compliance
  • Prospective Studies
  • Survival Analysis
  • Tacrolimus / administration & dosage*
  • Tacrolimus / adverse effects


  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Cyclosporine
  • Tacrolimus