To determine the effect of rituximab, when added to standard immunsuppressive therapy, on the incidence and severity of biopsy-confirmed acute rejection within the first six months after transplantation.
ID
Source
Brief title
Condition
- Immune disorders NEC
- Nephropathies
- Renal and urinary tract therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The incidence and severity of biopsy-confirmed acute rejection within the first
six months after transplantation.
Secondary outcome
- 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
Background 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 objective
To determine the effect of rituximab, when added to standard immunsuppressive
therapy, on the incidence and severity of biopsy-confirmed acute rejection
within the first six months after transplantation.
Study design
Double-blind, placebo controlled intervention study.
Intervention
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.
Study burden and risks
The main risks associated with participation are related to side effects of
rituximab, which can be divided in infusion related effects (fever, cough,
hypotension) and a potentially higher risk of infection. The number of
investigational procedures (including hospital visits and blood drawings) is
not different from standard treatment. At several visits, additional blood will
be drawn during a routine venapuncture (about 150 ml in two years).
Postbus 9101
6500 HB Nijmegen
NL
Postbus 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
1. All renal transplant recipients older than 18 years
2. All female patients at risk for pregnancy must have a negative serum pregnancy test before randomization. Female patients at risk for pregnancy must agree to use a medically acceptable method of contraception for 12 months after administration of study medication.
3. Signed, dated, and witnessed institutional review board (IRB) approved informed consent before screening and before any tests are performed that are specific to the protocol.
Exclusion criteria
1. Recipients of a kidney from a living donor, who is HLA identical.
2. Patients with hemolytic uremic syndrome as original kidney disease.
3. Patients with focal segmental glomerulosclerosis that had recurred in a previous graft
4. Recipients with more than two previously failed grafts and/or PRA > 85%
5. Previous treatment with anti-CD20 antibodies.
6. Diabetes mellitus that is currently not treated with insulin
7. Total white blood cell count <3,000/mm3 or platelet count <75,000/mm3.
8. Active infection with hepatitis B, hepatitis C, or HIV.
9. History of tuberculosis.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-001604-20-NL |
| CCMO | NL17180.091.07 |