Evaluation of Desensitization Protocols in HLA-incompatible Kidney-transplant Candidates
- Conditions
- End-stage Renal DiseaseKidney TransplantationHla-incompatible Kidney Transplant Candidates
- Interventions
- Drug: visits of tocilizumab injection (every 4 weeks, up to 5 visits)Other: Transplant Day-0
- Registration Number
- NCT03507348
- Lead Sponsor
- University Hospital, Grenoble
- Brief Summary
Kidney transplantation is the best renal-replacement in the setting of end-stage renal disease. However, some transplant candidates have developed anti-HLA alloantibodies (human leukocyte antigen). When they are numerous and when their strength assessed by mean fluorescence intensity (MFI) is high it is very complicated to find-out a suitable kidney allograft against which the recipient has a negative cross-match. In such a case the only hope for the patient is desensitization therapy, whereby the treatment will decrease anti-HLA alloantibodies below a threshold, i.e. MFI \< 3,000, enabling kidney transplantation without risking antibody-mediated rejection. Desensitization relies on i) apheresis technics in order to withdraw circulating anti-HLA antibodies, and ii) immunosuppression, i.e. rituximab or tocilizumab, targeting B-lymphocytes, and tacrolimus/mycophenolic acid/steroids targeting T-cells. The type of apheresis is guided by the pre-desensitization MFI of anti-HLA alloantibodies, e.g. double filtration plasmapheresis or semispecific immunoadsorption. Likely the choice between rituximab and tocilizumab depends also on predesensitization anti-HLA antibody MFIs. At the end of the desensitization process, the patient will be able to get a kidney transplant either from a live-donor or from a deceased donor.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 8
- Patients on the kidney transplant list, waiting for a first or repeat transplant
- Presence of anti HLA antibodies either class I and/or II
- Sensitized against a potential living donor or have been on the waiting list for at least 3 years and having no potential live-donor
- Patients eligible for desensitization will receive either rituximab alone, or rituximab plus apheresis, or tocilizumab before rituximab
- Normal recent (<6 months) cardiac workup
- Vaccinated against pneumococcus and meningococcus B and C
- Willingness of the patient to undergo the desensitization process and Express consent of the patient
- for women of childbearing age, effective contraception or abstinence
- Affiliated to a social security scheme or of such a scheme
- Active underlying infections or neoplasia
- Pregnant women, parturient or breastfeeding
- Subject in exclusion period of another study
- Subject under administrative or judicial control
- Subject who cannot be contacted in an emergency
- Rituximab contra indication: hypersensitivity (to active substance or murine protein), active and severe infections, patients in a severely immunocompromised state, severe heart failure or severe, uncontrolled cardiac disease.
- Tocilizumab contra indication: hypersensitivity, active and severe infections. Apheresis contra indication: active and severe infection, untreated or instable coagulation disorders, unstable coronary disease, recent stroke, hemodynamic instability.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Desensitization with Tocilizumab and rituximab (MFI >15000) visits of tocilizumab injection (every 4 weeks, up to 5 visits) - Desensitization with Tocilizumab and rituximab (MFI >15000) Rituximab 375 mg/m2 at Day-30 - Desensitization with Tocilizumab and rituximab (MFI >15000) Transplant Day-0 - Desensitization with Rituximab only (MFI<15000) Rituximab 375 mg/m2 at Day-30 - Desensitization with Rituximab only (MFI<15000) Rituximab 375 mg/m2 at Day-15 (only for donors living) - Desensitization with Rituximab only (MFI<15000) Transplant Day-0 - Desensitization with Tocilizumab and rituximab (MFI >15000) Rituximab 375 mg/m2 at Day-15 (only for donors living) -
- Primary Outcome Measures
Name Time Method Description of the results of the strategy of desensitization in patients who will access to kidney transplantation from deceased or living donors. at day 1 start of desensitization, at day 0 of Graft Decrease of MFI for highest donor-specific alloantibody (DSA) between start and end of desensitization for every patient in each category
- Secondary Outcome Measures
Name Time Method Desensitization efficacy with regards to DSA decrease and kidney transplantation Day-198, at day-30 Graft, at day-15, at day0 of Graft, MFI for highest DSAs for each group
impairment of DSA synthesis Day-198, at day-30 Graft, at day-15, at day0 of Graft, Decrease in peripheral plasma cells and plasmablasts of \>50%
Impairment of immune response Day-198, at day-30 Graft, at day-15, at day0 of Graft, Decrease in complement factors of \>25%
Incidence of treatment desensitization protocols, emergent adverse events (safety and Tolerability) Day-198, at day-30 Graft, at day-15 Emergent adverse events to the desensitization therapy will be carefully monitored during the treatment period and within the following three months.
Trial Locations
- Locations (1)
Grenoble Alpes University Hospital
🇫🇷La Tronche, France