Daclizumab Versus Thymoglobulin in Renal Transplant Recipients With High Immunological Risk (TAXI)

• Proportion of patients who experienced an acute rejection episode, whether confirmed by biopsy or not at 1 year. [ Time Frame: graft dysfunction ] [ Designated as safety issue: No ]
• Proportion of patients who experienced more than one episode of acute allograft rejection [ Time Frame: graft dysfunction, biopsies ] [ Designated as safety issue: No ]
• Proportion of patients who experienced an acute rejection episode that required therapy by anti-lymphocyte antibodies (ATG or OKT3) [ Time Frame: number of anti-lymphocyte treatment required for acute rejection episodes ] [ Designated as safety issue: No ]
• Number of acute rejection episodes per therapeutic arms and mean number of acute rejection episode per patient in each arm [ Time Frame: graft dysfunction and biopsies ] [ Designated as safety issue: No ]
• Banff grade of the first rejection episode [ Time Frame: graft biopsy ] [ Designated as safety issue: No ]
• Incidence of adverse events in the two treatment arms at 1 year [ Time Frame: number of adverse events reported by the investigators ] [ Designated as safety issue: Yes ]
• Incidence of delayed graft function [ Time Frame: number of patient who required hemodialysis during the first week post transplantation ] [ Designated as safety issue: Yes ]
• Graft function at 1 year [ Time Frame: serum creatinine and estimated glomerular filtration rate ] [ Designated as safety issue: No ]
• Graft and patient survival at 1 year [ Time Frame: number of graft failures and/or deaths ] [ Designated as safety issue: Yes ]

To compare renal allograft rejection rates during the first year among high-immunological risk recipients between patients who received either ATG or the anti-IL2R mAb daclizumab.

The objective of this randomized, multi-center trial is to directly compare the ATG, Thymoglobulin, with the anti-CD25 mAb, daclizumab, in a high-risk, HLA-sensitized renal transplant population, in order to elucidate whether there is any significant difference in the incidence of acute rejection after one year.

Eligible patients were randomized (1:1) to receive either ATG (1.25 mg/kg/d from day 0 to day 7) or daclizumab (1 mg/kg at days 0, 14, 28, 42 and 56). Maintenance immunosuppression comprised tacrolimus, MMF and prednisone. The study's primary endpoint was the incidence of biopsy-proven acute rejection at one year.

• Drug: Thymoglobulin (ATG)
  Thymoglobulin: 1.25 mg/kg per day from day 0 to day 7 post transplantation
  Other Name: Thymoglobulin, Genzyme
• Drug: Daclizumab
  Daclizumab: 1mg/kg at day 0, 14, 28, 42 and 56 post transplantation
  Other Name: Zenapax, Roche

• Active Comparator: 1, ATG
  Thymoglobulin induction during 8 days (1.25 mg/kg per day) associated with tacrolimus, mycophenolate mofetil and steroids
  Intervention: Drug: Thymoglobulin (ATG)
• Active Comparator: 2, Daclizumab
  Dacluzamb induction (five infusions, 1 mg/kg per infusion) associated with tacrolimus, mycophenolate mofetil and steroids
  Intervention: Drug: Daclizumab

Inclusion Criteria:

1. Third or fourth renal graft or
2. Current anti-HLA antibodies above or equal to 30% at the last evaluation or
3. Peak anti-HLA antibodies above or equal to 50% at the last evaluation or
4. A second graft if the first was lost within 2 years because of rejection.
5. Patients who gave their informed consent and are able to understand the scope of the study

Exclusion Criteria:

1. Transplantation from living donors or recipients of multiple grafts or patients who already have received another (non-renal) allograft.
2. Transplantation from a non-heart beating donor
3. Transplantation of two kidneys from the same donor
4. Patients with generalized infection at the time of transplantation
5. Women in child-bearing age who do not plan to use efficient contraception