Function of Renal Transplant
Conditions
Keywords
Immunosuppression, Rituximab, B cell
Brief summary
Hypothesis: * That B cell depletion, rather than reducing acute rejection, will allow minimisation of immunosuppression, which may lead to better graft survival. Aim: * To assess whether the addition of rituximab to a low-dose tacrolimus immunosuppression regime allows a reduction in steroid administration. Objectives: * To assess whether B cell depletion affects graft function, acute rejection and complication rates * To assess whether the T cell response to allotransplantation is impaired by B cell depletion.
Interventions
DRUGRituximab
375mg/m\^2, single dose given 2-4 weeks prior to transplantation
DRUGTacrolimus
dose calculated to give levels of 3-7ng/ml
Mycophenylate mofetil 2g/day in divided doses
DRUGHydrocortisone
100mg hydrocortisone on the evening of the day of surgery and 2 further doses of hydrocortisone on day 1 post transplant.
DRUGPrednisolone
Prednisolone 0.3mg/kg on day 2, 0.25mg/kg on day 3, 0.2mg/kg on day 4 and 0.16mg/kg on day 5. On day 6 they will receive 5mg prednisolone, and on day 7 none.
Sponsors
Astellas Pharma Europe Ltd.
Guy's and St Thomas' NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients over 18 years receiving their first living donor renal transplant, or their second if the first was not lost from acute rejection * Patients who have given written informed consent * Women of child bearing potential taking adequate contraception.
Exclusion criteria
* Previous other organ transplants lost through acute rejection * Patients undergoing antibody incompatible transplantation * Patients with other organ transplants * Patients previously treated with cyclophosphamide, ATG, OKT3 or rituximab * Patients with white cell count below 4.0x10\^9/L. * Patients with platelet count below 100x10\^9/L * Patients who are treated with drugs that are strong inhibitors or inducers of cytochrome P450, or treated with terfenadine, astemizole, cisapride or lovastatin * Patients who have been involved in any other investigational trial or non protocol immunosuppressive regimen in the previous 90 days prior to transplant * Pregnant or breastfeeding women * Patients with a documented history of malignancy and its origins and treatment in the last five years. (Localised basal cell carcinoma of the skin is permitted) * Patients known to be HIV, Hepatitis B surface antigen or Hepatitis C antibody positive * Patients who in the opinion of the Investigator would not be a suitable candidate for study participation * Women of child bearing potential not willing to take adequate contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Estimated GFR (calculated using the Cockcroft-Gault formula) | 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biopsy proven acute rejection (based on Banff classification) | 1, 2, 3, 4, 5 years | — |
| Allograft survival | 1, 2, 3, 4, 5 years | — |
| Patient Survival | 1, 2, 3, 4, 5 years | — |
| Infection rate | 1 year | New episodes, including (but not restricted to) viral (e.g. CMV, EBV), bacterial (e.g. Urinary Tract Infections with details of causative organism) and fungal infections will be recorded at each assessment time-point. |
| Changes in B and T cell repertoire | 1 year | — |
Countries
United Kingdom
Outcome results
None listed