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Rituximab for Prevention of Rejection After Renal Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Hoffmann-La Roche
Astellas Pharma GmbH
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT00565331
First received: November 28, 2007
Last updated: January 4, 2013
Last verified: October 2010
  Purpose

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 Intervention Phase
Kidney Transplantation
Drug: Rituximab
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Incidence and severity of biopsy-confirmed acute rejection [ Time Frame: First six months after transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Renal function as estimated by the endogenous creatinine clearance [ Time Frame: 6 months after transplantation ] [ Designated as safety issue: No ]
  • Occurrence of chronic allograft nephropathy [ Time Frame: First 6 months after transplantation ] [ Designated as safety issue: No ]
  • Cumulative incidence of infections and malignancies [ Time Frame: First 6 months after transplantation ] [ Designated as safety issue: Yes ]
  • Patient and graft survival [ Time Frame: First six months after transplantation ] [ Designated as safety issue: Yes ]

Enrollment: 280
Study Start Date: December 2007
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Rituximab
Drug: Rituximab
single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation
Other Name: Mabthera, Rituxan
Placebo Comparator: 2
Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565331

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Hoffmann-La Roche
Astellas Pharma GmbH
Investigators
Principal Investigator: Luuk Hilbrands, MD Radboud University
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT00565331     History of Changes
Other Study ID Numbers: RRT06, UMC Radboud RI000131
Study First Received: November 28, 2007
Last Updated: January 4, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014