Rituximab for Prevention of Rejection After Renal Transplantation

Sponsor

Radboud University Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00565331

Collaborator

Hoffmann-La Roche (Industry), Astellas Pharma GmbH (Industry)

280

Enrollment

Location

Arms

Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation	Drug: Rituximab Drug: Placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

280 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Dec 1, 2007

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Rituximab	Drug: Rituximab single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation Other Names: Mabthera, Rituxan
Placebo Comparator: 2 Placebo	Drug: Placebo saline solution

Arm

Intervention/Treatment

Active Comparator: 1

Rituximab

Drug: Rituximab

single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation

Other Names:

Mabthera, Rituxan

Placebo Comparator: 2

Placebo

Drug: Placebo

saline solution

Outcome Measures

Primary Outcome Measures

Incidence and severity of biopsy-confirmed acute rejection [First six months after transplantation]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radboud University Nijmegen Medical Centre	Nijmegen		Netherlands	6500 HB

Sponsors and Collaborators

Radboud University Medical Center
Hoffmann-La Roche
Astellas Pharma GmbH

Investigators

Principal Investigator: Luuk Hilbrands, MD, Radboud University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Radboud University Nijmegen Medical Centre

Publications

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.

Responsible Party:

Radboud University Medical Center

ClinicalTrials.gov Identifier:

NCT00565331

Other Study ID Numbers:

RRT06
UMC Radboud RI000131

First Posted:

Nov 29, 2007

Last Update Posted:

Nov 10, 2015

Last Verified:

Nov 1, 2015

Additional relevant MeSH terms:

Rituximab

Study Results

No Results Posted as of Nov 10, 2015