Graft Failure, Kidney Transplantation
Conditions
Keywords
Kidney transplantation, allosensitization, graft nephrectomy, Donor-Specific Antibodies
Brief summary
Graft nephrectomy is associated with massive allo-sensitization following this event. The occurrence of anti-HLA antibodies is a major barrier to perform a second kidney transplantation. Investigators propose here to evaluate in a phase II pilot study, the safety of the use of a single dose of Tocilizumab immediately before or after graft nephrectomy. The primary endpoint evaluated here is the occurrence of serious infectious complications following graft nephrectomy, with a treatment by Tocilizumab. Secondary endpoints evaluated here are - to evaluate all complications after graft nephrectomy, - and the Tocilizumab effectiveness to reduce anti-HLA antibodies at one year post nephrectomy.
Detailed description
Background: graft nephrectomy is associated with massive allo-sensitization following this event The occurrence of anti-HLA antibodies is a major barrier to perform a second kidney transplantation. Moreover, a systemic inflammatory response syndrome can occur which could lead to serious patient's complications, in case of early graft thrombosis. To date, no treatment or strategy is available to reduce these risks, after graft nephrectomy. IL-6 is a key cytokine in inflammation, but also in the development of T and B cells activation. This treatment previously demonstrated a major role in the occurrence of allo-antibodies. Tocilizumab is a monoclonal antibody blocking IL6 receptor, previously used with success in kidney transplantation to reduce anti-HLA antibodies mediated rejection. Objectives: Investigators hypothesize that Tocilizumab is useful to prevent allo-sensitization post graft nephrectomy. They propose here to evaluate in a phase II pilot study, the safety of the use of a single dose of Tocilizumab immediately before or after graft nephrectomy.
Interventions
DRUGTocilizumab
Tocilizumab will be administered at 8 mg/kg before or immediately after graft nephrectomy.
Sponsors
University Hospital, Toulouse
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult recipients, * affiliated to the social security * requiring a graft nephrectomy, with a project to retransplantation
Exclusion criteria
* combined transplantations, PRA \>20%. * Patient under protective measures, * Rituximab used for immunosuppression induction * Previous transplants not removed, * Active infectious complications at graft nephrectomy, need for immunosuppressive treatments after graft nephrectomy, * Participation to another interventional studies using Rituximab, polyclonal antibodies, Eculizumab, or Tocilizumab. * adults under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision, * pregnancy or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| serious infectious complication | 1 year post graft nephrectomy | serious infectious complication rate at 1 year post graft nephrectomy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complications after treatment | 1 year post graft nephrectomy | Safety excluding serious infectious complications one year after nephrectomy, used by: * The occurrence of post-nephrectomy complications * The occurrence of death * The occurrence of hospitalizations * The occurrence of surgical complications * The occurrence of infectious complications (mild and moderate) |
| The effectiveness of the treatment | 1 year post graft nephrectomy | The effectiveness of the treatment assessed by the rate of immunization after a post nephrectomy |
Countries
France
Outcome results
None listed