Rituximab for Prevention of Rejection After Renal Transplantation

Phase 2

Completed

• Conditions: Kidney Transplantation
• Interventions: Drug: Rituximab; Drug: Placebo

• Registration Number: NCT00565331
• Lead Sponsor: Radboud University Medical Center

Brief 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2007-11-28
• Study First Submitted QC: 2007-11-28
• Study First Posted: 2007-11-29
• Study Start: 2007-12
• Primary Completion: 2013-12
• Study Completion: 2015-06
• Status Verified: 2015-11
• Last Update Submitted: 2015-11-09
• Last Update Posted: 2015-11-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 280

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Rituximab	Rituximab
2	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
Incidence and severity of biopsy-confirmed acute rejection	First six months after transplantation

Secondary Outcome Measures

Name	Time	Method
Occurrence of chronic allograft nephropathy	First 6 months after transplantation
Patient and graft survival	First six months after transplantation
Renal function as estimated by the endogenous creatinine clearance	6 months after transplantation
Cumulative incidence of infections and malignancies	First 6 months after transplantation

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Centre; 🇳🇱 Nijmegen, Netherlands