Kidney TransplantationPhase 2/3NCT00565331
Rituximab for Prevention of Rejection After Renal Transplantation
A Phase 2/3 study testing Rituximab in people with Kidney Transplantation, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 280 participants
- Where
- 1 siteNetherlands
- Study dates
- Dec 2007to Jun 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Renal transplant recipients
- Signed, dated, and witnessed IRB approved informed consent
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, 6500 HB
About this study
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
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.
Read more
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
- Conditions
- Kidney Transplantation
- Being tested
- Rituximab, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Mabthera, Rituxan
single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation
PlaceboDrug
saline solution
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Rituximab Receives: Drug: Rituximab |
| 2 | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of biopsy-confirmed acute rejection
Measured: First six months after transplantation
Secondary outcomes (4)
Renal function as estimated by the endogenous creatinine clearance
Measured: 6 months after transplantation
Occurrence of chronic allograft nephropathy
Measured: First 6 months after transplantation
Cumulative incidence of infections and malignancies
Measured: First 6 months after transplantation
Patient and graft survival
Measured: First six months after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2007 (estimated)
- Study startDec 2007
- Primary completionDec 2013
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche, Astellas Pharma GmbH
- Responsible party
- Sponsor
- Investigators
- Luuk Hilbrands, MD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00565331
- Sponsor's protocol ID
- RRT06
- Other IDs
- UMC Radboud RI000131
- Status last verified
- Nov 2015
- First submitted
- 28 Nov 2007
- Last updated
- 10 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.1111/j.1600-6143.2006.01288.x.
PubMed 16611321Kamburova 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.
PubMed 25393622Smeekens 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.
PubMed 23651756
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00565331
- Acronym / sponsor ID
- RRT06
- Conditions
- Kidney Transplantation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 280 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche, Astellas Pharma GmbH
- Study start
- Dec 2007
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 29 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: RituximabRituximab |
| 2 | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Renal transplant recipients
- Signed, dated, and witnessed IRB approved informed consent
Key exclusion criteria (10 listed)
- 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%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: Mabthera, Rituxansingle dose of rituximab of 375 mg/m2 intravenously at the time of transplantation | Drug | 1 |
| Placebosaline solution | Drug | 2 |
Primary outcome
Incidence and severity of biopsy-confirmed acute rejection
Time frame: First six months after transplantation
4 secondary outcomes
Renal function as estimated by the endogenous creatinine clearance
Time frame: 6 months after transplantation
Occurrence of chronic allograft nephropathy
Time frame: First 6 months after transplantation
Cumulative incidence of infections and malignancies
Time frame: First 6 months after transplantation
Patient and graft survival
Time frame: First six months after transplantation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2015.
- Background: PubMed 16611321Pescovitz 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.
- Derived from this study: PubMed 25393622Kamburova 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.
- Derived from this study: PubMed 23651756Smeekens 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.
- Radboud University Nijmegen Medical CentreLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luuk Hilbrands, MD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Rituximab in people with Kidney Transplantation, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of biopsy-confirmed acute rejection (time frame: First six months after transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00565331, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2015.