Clinical trial NCT00682292: Daclizumab Versus Thymoglobulin in Renal Transplant Recipients With High Immunological Risk
Official title: 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: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Renal Transplantation
Keywords: Renal transplantation
Immunisation
Acute rejection
Induction therapy
Thymoglobulin
Daclizumab
Rejection in sensitized renal transplant recipients
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Erasme University Hospital
First posted: 2008-05-22
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of biopsy-proven acute allograft rejection during the first post-transplant year
timeFrame: acute rejection proved by graft biopsy
Secondary outcomes:
measure: Proportion of patients who experienced an acute rejection episode, whether confirmed by biopsy or not at 1 year.
timeFrame: graft dysfunction
measure: Proportion of patients who experienced more than one episode of acute allograft rejection
timeFrame: graft dysfunction, biopsies
measure: Proportion of patients who experienced an acute rejection episode that required therapy by anti-lymphocyte antibodies (ATG or OKT3)
timeFrame: number of anti-lymphocyte treatment required for acute rejection episodes
measure: Number of acute rejection episodes per therapeutic arms and mean number of acute rejection episode per patient in each arm
timeFrame: graft dysfunction and biopsies
measure: Banff grade of the first rejection episode
timeFrame: graft biopsy
measure: Incidence of adverse events in the two treatment arms at 1 year
timeFrame: number of adverse events reported by the investigators
measure: Incidence of delayed graft function
timeFrame: number of patient who required hemodialysis during the first week post transplantation
measure: Graft function at 1 year
timeFrame: serum creatinine and estimated glomerular filtration rate
measure: Graft and patient survival at 1 year
timeFrame: number of graft failures and/or deaths
Other outcomes:
Locations:
city: Lille
country: France
facility: University Hospital of Lille
Study officials:
affiliation: University Hospital of Lille, France
name: Christian Noël, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Erasme Hospital, Bruxelles, Belgium
name: Daniel Abramowicz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: