Kidney TransplantationPhase 2RAPTURENCT00371904
Trial of Rituximab Given Pre-Transplant to Sensitised Live Donor Kidney Recipients
A Phase 2 study testing Rituximab in people with Kidney Transplantation, run by Hunter and New England Health at 3 sites in Australia.
Trial summary
About one third of prospective kidney transplant recipients have antibodies in their blood directed against the tissues of their only available kidney donor. Recently, "desensitisation" treatments when administered pre-transplant have allowed successful transplantation of these patients despite high rates of acute… 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?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 3 sitesAustralia
- Study dates
- Apr 2006to Jan 2009
- Phase
- Phase 2
- 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
- Subjects, age > 18 years
- Subjects receiving a single organ renal transplant from a living donor
- Positive T-cell and/or B-cell crossmatch by complement dependent cytotoxicity (CDC) and/or positive flow cytometry crossmatch with confirmed donor-specific antibodies on solid-phase assay at screening. Positive CDC T-cell and/or B-cell crossmatch titre must be less than or equal to 1:64.
- Subjects capable of understanding the purposes and risks of the study and who can give written informed consent
- Exclusion Criteria at Study Entry (4 weeks prior to transplant):
- Primary renal transplant lost from acute rejection less than six months prior to randomisation
Show all 18Show fewer
- Women of childbearing potential with a positive serum or urine pregnancy test or nursing mothers
- Subjects with history of malignancy (other than non melanoma skin cancer that has been totally excised with no recurrence for two years)
- Subjects with known contraindications to treatment with rituximab
- Subjects with haemoglobin < 8.5 g/dL, WBC value of < 3000/mm3 or a platelet count of < 50,000/mm3 that is unlikely to resolve prior to randomisation
- Subjects with a positive ABO crossmatch with donor
- Subjects with severe diarrhoea or other gastrointestinal disorders that might interfere with the ability to absorb oral medication and is unlikely to resolve prior to randomisation
- Subjects participating in another interventional clinical trial or requiring treatment with un-marketed investigational drugs or who would be expected to require other medications prohibited by the protocol
- Subjects who cannot be followed for the study duration
- Subjects with disorders or conditions that may interfere with the ability to comply with study procedures and/or requirements
- Additional Exclusion Criteria at Day -2 before Transplantation:
- All exclusion criteria as at study entry
- Positive T- and/or B-cell CDC crossmatch at Day -2
Who cannot join
None listed.
Trial locations and contacts
3 sites in 1 country.
Australia3 sites, 3 recruiting
- Not yet recruiting
Monash Medical Centre
Clayton, Victoria, 3168
John Kanellis, MBBS, PhD, FRACP, +61395943070, john.kanellis@med.monash.edu.au
Janet Andrew, +61395943526, j.andrew@southernhealth.org.au
- Recruiting
Newcastle Transplant Unit, John Hunter Hospital
Newcastle, New South Wales, 2305
Paul R Trevillian, MBBS, FRACP, +61249214326, Paul.Trevillian@hnehealth.nsw.gov.au
Ann Stein, RN, +61249214341, Ann.Stein@hnehealth.nsw.gov.au
- Not yet recruiting
Royal Melbourne Hospital
Parkville, Victoria, 3052
Shlomo Cohney, MBBS, +61393427159, Solomon.Cohney@wh.org.au
Maria Farrell, +61393427077, maria.farrell@mh.org.au
About this study
Official title: A Prospective Open Label Randomised Multicentre Study Evaluating the Efficacy & Safety of Rituximab Given Pre-Transplant to Sensitised Renal Allograft Recipients in Addition to a "Standard" Desensitisation Regimen Consisting of PE/IVIG & MMF
About one third of prospective kidney transplant recipients have antibodies in their blood directed against the tissues of their only available kidney donor. Recently, "desensitisation" treatments when administered pre-transplant have allowed successful transplantation of these patients despite high rates of acute antibody mediated rejection (AAMR). The investigators propose to test in a randomised controlled trial whether rituximab, a monoclonal antibody that depletes B-lymphocytes, will safely lower antibody mediated rejection (AMR) rates when added to "standard" therapy. The investigators will also test whether rituximab enables more patients to achieve a negative crossmatch against their donor and thereby allow more transplants to proceed.
Read the detailed description
This study is designed to investigate in a prospective, randomised fashion whether a single intravenous dose of rituximab (375 mg/m2) given two weeks prior to transplant, in addition to standard therapy, will allow sensitised renal transplant subjects to achieve a negative CDC crossmatch and thereby proceed to live donor transplantation. We will also evaluate whether rituximab will reduce the number of AAMR episodes in the post-transplant period, compared to controls. All eligible subjects must have a positive T- and/or B-cell CDC or flow cytometry crossmatch and have donor-specific antibodies identified by solid-phase assay at screening. All subjects will receive a standard desensitisation regimen that includes plasma exchange/IVIG + MMF before and immediately after transplantation followed by a standard care immunosuppressive regimen (IL-2R antagonist, tacrolimus, mycophenolate mofetil [MMF] and corticosteroids) after transplantation.
- Conditions
- Kidney Transplantation
- Being tested
- Rituximab, Standard Care
- Keywords
- Rituximab, donor, sensitised, antibody, rejection
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Mabthera
Single dose (375 mg/m2) of rituximab to be given intravenously (IV) 14 days prior to transplantation
Standard CareDrug
Standard care
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Rituximab |
| 2 | Active comparator | Not described Receives: Drug: Standard Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biopsy proven antibody mediated rejection
Measured: 12 months
Secondary outcomes (12)
Elimination of donor specific antibodies (DSA)
Measured: Day - 2 , 7; Months 1, 3, 6, 9 and 12
C4d in biopsies
Measured: Day 7; Months 3 and 12
Plasma exchanges
Measured: Month 12
Death
Measured: Month 12
Treated rejection
Measured: Month 12
Graft loss
Measured: Months 3, 6 and 12
Treatment failure
Measured: Months 6 and 12
Calculation of glomerular filtration rate (GFR)
Measured: Months 1 - 12
Slope of 1/serum creatinine (Ser. Cr)
Measured: Months 6 and 12
24-hour U protein
Measured: Months 3 and 12
Safety
Measured: Month 12
Cancer and infections
Measured: Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2006 (estimated)
- Study startApr 2006
- Study completionJan 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 192 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hunter and New England Health
- Sponsor type
- University, hospital or other
- Collaborators
- Melbourne Health, Princess Alexandra Hospital, Brisbane, Australia, Royal Prince Alfred Hospital, Sydney, Australia, Auckland City Hospital, Monash Medical Centre, Royal Perth Hospital, Westmead Hospital, Royal Adelaide Hospital
- Investigators
- Paul R Trevillian, MBBS, FRACP, Study chair, Newcastle Transplant Unit, John Hunter HospitalSolomon Cohney, MBBS, FRACP, PhD, Study chair, Melbourne Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00371904
- Sponsor's protocol ID
- RAPTURE
- Acronym
- RAPTURE
- Status last verified
- May 2008
- First submitted
- 1 Sep 2006
- Last updated
- 21 May 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Open Label Randomised Multicentre Study Evaluating the Efficacy & Safety of Rituximab Given Pre-Transplant to Sensitised Renal Allograft Recipients in Addition to a "Standard" Desensitisation Regimen Consisting of PE/IVIG & MMF
- ClinicalTrials.gov ID
- NCT00371904
- Acronym / sponsor ID
- RAPTURE / RAPTURE
- Conditions
- Kidney Transplantation
- Keywords
- Rituximab, donor, sensitised, antibody, rejection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 192 participants (estimated)
- Lead sponsor
- Hunter and New England HealthUniversity, hospital or other
- Collaborators
- Melbourne Health, Princess Alexandra Hospital, Brisbane, Australia, Royal Prince Alfred Hospital, Sydney, Australia, Auckland City Hospital, Monash Medical Centre, Royal Perth Hospital, Westmead Hospital, Royal Adelaide Hospital
- Study start
- Apr 2006
- Study completion
- Jan 2009 (estimated)
- First posted
- 4 Sep 2006 (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.
About one third of prospective kidney transplant recipients have antibodies in their blood directed against the tissues of their only available kidney donor. Recently, "desensitisation" treatments when administered pre-transplant have allowed successful transplantation of these patients despite high rates of acute antibody mediated rejection (AAMR). The investigators propose to test in a randomised controlled trial whether rituximab, a monoclonal antibody that depletes B-lymphocytes, will safely lower antibody mediated rejection (AMR) rates when added to "standard" therapy. The investigators will also test whether rituximab enables more patients to achieve a negative crossmatch against their donor and thereby allow more transplants to proceed.
Detailed description
This study is designed to investigate in a prospective, randomised fashion whether a single intravenous dose of rituximab (375 mg/m2) given two weeks prior to transplant, in addition to standard therapy, will allow sensitised renal transplant subjects to achieve a negative CDC crossmatch and thereby proceed to live donor transplantation. We will also evaluate whether rituximab will reduce the number of AAMR episodes in the post-transplant period, compared to controls. All eligible subjects must have a positive T- and/or B-cell CDC or flow cytometry crossmatch and have donor-specific antibodies identified by solid-phase assay at screening. All subjects will receive a standard desensitisation regimen that includes plasma exchange/IVIG + MMF before and immediately after transplantation followed by a standard care immunosuppressive regimen (IL-2R antagonist, tacrolimus, mycophenolate mofetil [MMF] and corticosteroids) after transplantation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Rituximab |
| 2 | Active comparator | Drug: Standard Care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Subjects, age > 18 years
- Subjects receiving a single organ renal transplant from a living donor
- Positive T-cell and/or B-cell crossmatch by complement dependent cytotoxicity (CDC) and/or positive flow cytometry crossmatch with confirmed donor-specific antibodies on solid-phase assay at screening. Positive CDC T-cell and/or B-cell crossmatch titre must be less than or equal to 1:64.
- Subjects capable of understanding the purposes and risks of the study and who can give written informed consent
- Primary renal transplant lost from acute rejection less than six months prior to randomisation
Key exclusion criteria (0 listed)
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: MabtheraSingle dose (375 mg/m2) of rituximab to be given intravenously (IV) 14 days prior to transplantation | Drug | 1 |
| Standard CareStandard care | Drug | 2 |
Primary outcome
Biopsy proven antibody mediated rejection
Time frame: 12 months
12 secondary outcomes
Elimination of donor specific antibodies (DSA)
Time frame: Day - 2 , 7; Months 1, 3, 6, 9 and 12
C4d in biopsies
Time frame: Day 7; Months 3 and 12
Plasma exchanges
Time frame: Month 12
Death
Time frame: Month 12
Treated rejection
Time frame: Month 12
Graft loss
Time frame: Months 3, 6 and 12
Treatment failure
Time frame: Months 6 and 12
Calculation of glomerular filtration rate (GFR)
Time frame: Months 1 - 12
Slope of 1/serum creatinine (Ser. Cr)
Time frame: Months 6 and 12
24-hour U protein
Time frame: Months 3 and 12
Safety
Time frame: Month 12
Cancer and infections
Time frame: Month 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2008.
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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.
Paul R Trevillian, MBBS, FRACP study chair
Newcastle Transplant Unit, John Hunter Hospital
Solomon Cohney, MBBS, FRACP, PhD study chair
Melbourne Health
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Kidney Transplantation, run by Hunter and New England Health at 3 sites in Australia.
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 18 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 21 May 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Paul R Trevillian, MBBS, FRACP (+61414417311, Paul.Trevillian@hnehealth.nsw.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biopsy proven antibody mediated rejection (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 May 2008.