Daclizumab Versus Thymoglobulin in Renal Transplant Recipients With High Immunological Risk

Overview

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.

Full Title of Study: “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.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2006

Detailed Description

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.

Interventions

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

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

Primary Measures

  • Incidence of biopsy-proven acute allograft rejection during the first post-transplant year
    • Time Frame: acute rejection proved by graft biopsy

Secondary Measures

  • Proportion of patients who experienced an acute rejection episode, whether confirmed by biopsy or not at 1 year.
    • Time Frame: graft dysfunction
  • Proportion of patients who experienced more than one episode of acute allograft rejection
    • Time Frame: graft dysfunction, biopsies
  • 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
  • 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
  • Banff grade of the first rejection episode
    • Time Frame: graft biopsy
  • Incidence of adverse events in the two treatment arms at 1 year
    • Time Frame: number of adverse events reported by the investigators
  • Incidence of delayed graft function
    • Time Frame: number of patient who required hemodialysis during the first week post transplantation
  • Graft function at 1 year
    • Time Frame: serum creatinine and estimated glomerular filtration rate
  • Graft and patient survival at 1 year
    • Time Frame: number of graft failures and/or deaths

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital, Lille
  • Collaborator
    • Erasme University Hospital
  • Provider of Information About this Clinical Study
    • Noël Christian, MD, PhD, Professor of Nephrology, University Hospital of Lille
  • Overall Official(s)
    • Christian Noël, MD, PhD, Principal Investigator, University Hospital of Lille, France
    • Daniel Abramowicz, MD, PhD, Principal Investigator, Erasme Hospital, Bruxelles, Belgium

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