RituxiMab INDuction in Renal Transplantation

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Trial of Rituximab in Induction Therapy for Living Donor Renal Transplantation

Conditions
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Function of Renal Transplant

Intervention / Treatment
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* Drug: Rituximab
* Drug: Tacrolimus
* Drug: Mycophenylate mofetil
* Drug: Hydrocortisone
* Drug: Prednisolone
* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>Rituximab 375mg/m2 Low dose tacrolimus with mycophenylate mofetil, hydrocortisone and 1 week prednisolone | Drug: Rituximab<br>* 375mg/m^2, single dose given 2-4 weeks prior to transplantation<br>* Other names: Mabthera;Drug: Tacrolimus<br>* dose calculated to give levels of 3-7ng/ml<br>* Other names: Advagraf, Adoport, Prograf;Drug: Mycophenylate mofetil<br>* Mycophenylate mofetil 2g/day in divided doses<br>* Other names: MMF, Cellcept;Drug: Hydrocortisone<br>* 100mg hydrocortisone on the evening of the day of surgery and 2 further doses of hydrocortisone on day 1 post transplant.<br>Drug: Prednisolone<br>* 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.<br>|
| Active Comparator: Control group<br>Low dose tacrolimus with mycophenylate mofetil and continued prednisolone | Drug: Tacrolimus<br>* dose calculated to give levels of 3-7ng/ml<br>* Other names: Advagraf, Adoport, Prograf;Drug: Mycophenylate mofetil<br>* Mycophenylate mofetil 2g/day in divided doses<br>* Other names: MMF, Cellcept;Drug: Hydrocortisone<br>* 100mg hydrocortisone on the evening of the day of surgery and 2 further doses of hydrocortisone on day 1 post transplant.<br>Drug: Prednisolone<br>* Reducing dose of prednisolone over at least 6 months. Subsequent steroid maintenance or withdrawal will be at the discretion of the patient's clinician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated GFR (calculated using the Cockcroft-Gault formula) |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 1 year | 
| Changes in B and T cell repertoire |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunosuppression, Rituximab, B cell