Rituximab for Prevention of Rejection After Renal Transplantation

Study Overview
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Brief Summary
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Our standard immunosuppressive treatment after renal transplantation is a combination of tacrolimus, mycophenolate mofetil, and prednisolone. With this regimen the incidence of acute rejection within the first six months after transplantation has dropped to about 20%. The main challenge at present remains to improve long-term outcome by preventing chronic allograft nephropathy (CAN). Since acute rejection is a strong predictor of CAN, a further decrease in the incidence of acute rejection can improve the long-term graft survival. Current strategies to prevent rejection are mainly directed at alloreactive T cells. Recently, the attention for the role of antibodies in the pathogenesis of acute rejection has increased. In addition, anti-B cell therapy was shown to be effective in diseases that were considered to be mainly T cell driven, like rheumatoid arthritis. In the latter case it has been suggested that anti-B cell antibodies may impair the antigen presenting function of B cells. We therefore decided to investigate the effectiveness and safety of the anti-B cell monoclonal antibody rituximab for prophylaxis of acute rejection after renal transplantation. Study design: Double-blind, placebo controlled intervention study. One group receives a single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation, and the other group receives a placebo infusion. Primary Objective: To determine the incidence and severity of biopsy-confirmed acute rejection within the first six months after transplantation. Secondary Outcomes: Renal function as estimated by the endogenous creatinine clearance at 6 months Occurrence of chronic allograft nephropathy at 6 months Cumulative incidence of infections and malignancies at 6 months Medical costs during the first 6 months after transplantation Patient and graft survival

Official Title
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A Prospective Randomized Study on the Efficacy and Safety of the Prophylactic Use of Rituximab, Added to Standard Immunosuppressive Treatment in Comparison With Standard Immunosuppressive Treatment Alone in Renal Transplantation

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Rituximab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplant recipients Signed, dated, and witnessed IRB approved informed consent Exclusion Criteria: Pregnancy Living donor, who is HLA identical. Hemolytic uremic syndrome as original kidney disease. Focal segmental glomerulosclerosis that had recurred in a previous graft. More than two previously failed grafts and/or PRA > 85%. Previous treatment with anti-CD20 antibodies. Diabetes mellitus that is currently not treated with insulin. Total white blood cell count <3,000/mm3 or platelet count <75,000/mm3. Active infection with hepatitis B, hepatitis C, or HIV. History of tuberculosis

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Rituximab | Drug: Rituximab<br>* single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation<br>* Other names: Mabthera, Rituxan;|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of biopsy-confirmed acute rejection |  | First six months after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal function as estimated by the endogenous creatinine clearance |  | 6 months after transplantation | 
| Occurrence of chronic allograft nephropathy |  | First 6 months after transplantation | 
| Cumulative incidence of infections and malignancies |  | First 6 months after transplantation | 
| Patient and graft survival |  | First six months after transplantation |