Daclizumab Versus Thymoglobulin in Renal Transplant Recipients With High Immunological Risk

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Multicenter Randomized Study to Compare Induction Therapy With Polyclonal Antithymocytes Globulins (ATG) Versus Monoclonal Anti-IL2R Antibody (Daclizumab) in a Triple Drug Regimen in Renal Transplant Recipients With High Immunological Risk.

Conditions
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Renal Transplantation

Intervention / Treatment
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* Drug: Thymoglobulin (ATG)
* Drug: Daclizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Third or fourth renal graft or Current anti-HLA antibodies above or equal to 30% at the last evaluation or Peak anti-HLA antibodies above or equal to 50% at the last evaluation or A second graft if the first was lost within 2 years because of rejection. Patients who gave their informed consent and are able to understand the scope of the study Exclusion Criteria: Transplantation from living donors or recipients of multiple grafts or patients who already have received another (non-renal) allograft. Transplantation from a non-heart beating donor Transplantation of two kidneys from the same donor Patients with generalized infection at the time of transplantation Women in child-bearing age who do not plan to use efficient contraception

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1, ATG<br>Thymoglobulin induction during 8 days (1.25 mg/kg per day) associated with tacrolimus, mycophenolate mofetil and steroids | Drug: Thymoglobulin (ATG)<br>* Thymoglobulin: 1.25 mg/kg per day from day 0 to day 7 post transplantation<br>* Other names: Thymoglobulin, Genzyme;|
| Active Comparator: 2, Daclizumab<br>Dacluzamb induction (five infusions, 1 mg/kg per infusion) associated with tacrolimus, mycophenolate mofetil and steroids | Drug: Daclizumab<br>* Daclizumab: 1mg/kg at day 0, 14, 28, 42 and 56 post transplantation<br>* Other names: Zenapax, Roche;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of biopsy-proven acute allograft rejection during the first post-transplant year |  | acute rejection proved by graft biopsy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who experienced an acute rejection episode, whether confirmed by biopsy or not at 1 year. |  | graft dysfunction | 
| Proportion of patients who experienced more than one episode of acute allograft rejection |  | graft dysfunction, biopsies | 
| Proportion of patients who experienced an acute rejection episode that required therapy by anti-lymphocyte antibodies (ATG or OKT3) |  | number of anti-lymphocyte treatment required for acute rejection episodes | 
| Number of acute rejection episodes per therapeutic arms and mean number of acute rejection episode per patient in each arm |  | graft dysfunction and biopsies | 
| Banff grade of the first rejection episode |  | graft biopsy | 
| Incidence of adverse events in the two treatment arms at 1 year |  | number of adverse events reported by the investigators | 
| Incidence of delayed graft function |  | number of patient who required hemodialysis during the first week post transplantation | 
| Graft function at 1 year |  | serum creatinine and estimated glomerular filtration rate | 
| Graft and patient survival at 1 year |  | number of graft failures and/or deaths | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal transplantation, Immunisation, Acute rejection, Induction therapy, Thymoglobulin, Daclizumab, Rejection in sensitized renal transplant recipients