Clinical trial NCT00565331: Rituximab for Prevention of Rejection After Renal Transplantation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Kidney Transplantation
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
name: Astellas Pharma GmbH
First posted: 2007-11-29
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Incidence and severity of biopsy-confirmed acute rejection
timeFrame: First six months after transplantation
Secondary outcomes:
measure: Renal function as estimated by the endogenous creatinine clearance
timeFrame: 6 months after transplantation
measure: Occurrence of chronic allograft nephropathy
timeFrame: First 6 months after transplantation
measure: Cumulative incidence of infections and malignancies
timeFrame: First 6 months after transplantation
measure: Patient and graft survival
timeFrame: First six months after transplantation
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
Study officials:
affiliation: Radboud University Medical Center
name: Luuk Hilbrands, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. Am J Transplant. 2006 May;6(5 Pt 1):859-66. doi: 10.1111/j.1600-6143.2006.01288.x.
citation: Kamburova EG, Koenen HJ, van den Hoogen MW, Baas MC, Joosten I, Hilbrands LB. Longitudinal analysis of T and B cell phenotype and function in renal transplant recipients with or without rituximab induction therapy. PLoS One. 2014 Nov 13;9(11):e112658. doi: 10.1371/journal.pone.0112658. eCollection 2014.
citation: Smeekens SP, van den Hoogen MW, Kamburova EG, van de Veerdonk FL, Joosten I, Koenen HJ, Netea MG, Hilbrands LB, Joosten LA. The effects of in vivo B-cell depleting therapy on ex-vivo cytokine production. Transpl Immunol. 2013 Jun;28(4):183-8. doi: 10.1016/j.trim.2013.04.008. Epub 2013 May 4.