Rituximab for Prevention of Rejection After Renal Transplantation

• Status: Completed
• Trial end date: 2015-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Radboud University
• Collaborators: Astellas Pharma GmbH; Hoffmann-La Roche
• Treatments: Rituximab

Criteria

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