Rituximab for Prevention of Rejection After Renal Transplantation

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00565331
• Other study ID #: RRT06
• Secondary ID: UMC Radboud RI00
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: November 28, 2007
• Last updated: November 9, 2015
• Start date: December 2007
• Est. completion date: June 2015

Study information

• Verified date: November 2015
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 280
• Est. completion date: June 2015
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• Rituximab
single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation
• Placebo
saline solution

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University	Astellas Pharma GmbH, Hoffmann-La Roche

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. Am J Transplant. 2006 May;6(5 Pt 1):859-66. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of biopsy-confirmed acute rejection		First six months after transplantation	No
Secondary	Renal function as estimated by the endogenous creatinine clearance		6 months after transplantation	No
Secondary	Occurrence of chronic allograft nephropathy		First 6 months after transplantation	No
Secondary	Cumulative incidence of infections and malignancies		First 6 months after transplantation	Yes
Secondary	Patient and graft survival		First six months after transplantation	Yes

External Links

•   Radboud University Nijmegen Medical Centre