Rituximab for Prevention of Rejection After Renal Transplantation

November 9, 2015 updated by: Radboud University Medical Center

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

280

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Nijmegen, Netherlands, 6500 HB
        • Radboud University Nijmegen Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence and severity of biopsy-confirmed acute rejection
Time Frame: First six months after transplantation
First six months after transplantation

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

Hoffmann-La Roche
Astellas Pharma GmbH

Investigators

  • Principal Investigator: Luuk Hilbrands, MD, Radboud university medical center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (ACTUAL)

December 1, 2013

Study Completion (ACTUAL)

June 1, 2015

Study Registration Dates

First Submitted

November 28, 2007

First Submitted That Met QC Criteria

November 28, 2007

First Posted (ESTIMATE)

November 29, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

November 10, 2015

Last Update Submitted That Met QC Criteria

November 9, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RRT06
  • UMC Radboud RI000131

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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