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

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.

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.

Study Overview

• Status: Completed
• Conditions: Renal Transplantation
• Intervention / Treatment: Drug: Thymoglobulin (ATG); Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Lille, France, 59037
    • University Hospital of Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Erasme University Hospital
• Investigators: Principal Investigator: Christian Noël, MD, PhD, University Hospital of Lille, France; Principal Investigator: Daniel Abramowicz, MD, PhD, Erasme Hospital, Bruxelles, Belgium

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): November 1, 2006
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: May 20, 2008
• First Submitted That Met QC Criteria: May 21, 2008
• First Posted (Estimate): May 22, 2008

Study Record Updates

• Last Update Posted (Estimate): May 22, 2008
• Last Update Submitted That Met QC Criteria: May 21, 2008
• Last Verified: February 1, 2004

More Information

Terms related to this study

• Keywords: Thymoglobulin; Immunisation; Acute rejection; Renal transplantation; Daclizumab; Induction therapy; Rejection in sensitized renal transplant recipients
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Thymoglobulin; Antilymphocyte Serum; Daclizumab
• Other Study ID Numbers: UHLillle; CRG020600038