Rituximab for Prevention of Rejection After Renal Transplantation

Radboud University Medical Center

Status and phase: Completed; Phase 3; Phase 2

Conditions: Kidney Transplantation

Treatments: Drug: Rituximab; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00565331

RRT06

UMC Radboud RI000131

Details and patient eligibility

About

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

Enrollment: 280 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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280 participants in 2 patient groups, including a placebo group

1

Active Comparator group

Description:

Rituximab

Treatment:

Drug: Rituximab

2

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo