Trial of Rituximab Given Pre-Transplant to Sensitised Live Donor Kidney Recipients (RAPTURE)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2008 by Hunter and New England Health.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Melbourne Health
Princess Alexandra Hospital, Brisbane, Australia
Royal Prince Alfred Hospital, Sydney, Australia
Auckland City Hospital, New Zealand
Monash Medical Centre
Royal Perth Hospital
Westmead Hospital
Royal Adelaide Hospital
Information provided by:
Hunter and New England Health
ClinicalTrials.gov Identifier:
NCT00371904
First received: September 1, 2006
Last updated: May 20, 2008
Last verified: May 2008

September 1, 2006
May 20, 2008
April 2006
Not Provided
Biopsy proven antibody mediated rejection [ Time Frame: 12 months ]
The incidence of biopsy proven, antibody mediated rejection (both clinical and subclinical) at 12 months
Complete list of historical versions of study NCT00371904 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Elimination of DSA - Day -2 , 7, Mos 1, 3, 6, 9 & 12.
  • C4d in biopsies - Day 7, Mo 3 & 12.
  • Plasma exchanges - Mo 12.
  • Death - Mo 12.
  • Treated rejection - Mo 12.
  • Graft loss - Mo 3, 6 & 12.
  • Treatment failure - Mo 6 & 12
  • Calc. GFR - Mos 1-12.
  • Slope of 1/Ser. Cr - Mo 6 & 12.
  • 24-hr U protein - Mo 3 & 12.
  • Safety at Mo 12 - cancer & infections.
Not Provided
Not Provided
 
Trial of Rituximab Given Pre-Transplant to Sensitised Live Donor Kidney Recipients
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Kidney Transplantation
  • Drug: Rituximab
    Single dose (375 mg/m2) of rituximab to be given intravenously (IV) 14 days prior to transplantation
    Other Name: Mabthera
  • Drug: Standard Care
    Standard care
  • Experimental: 1
    Intervention: Drug: Rituximab
  • Active Comparator: 2
    Intervention: Drug: Standard Care
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
192
January 2009
Not Provided

Inclusion criteria:

  1. Subjects, age > 18 years
  2. Subjects receiving a single organ renal transplant from a living donor
  3. 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.
  4. 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):

  1. Primary renal transplant lost from acute rejection less than six months prior to randomisation
  2. Women of childbearing potential with a positive serum or urine pregnancy test or nursing mothers
  3. Subjects with history of malignancy (other than non melanoma skin cancer that has been totally excised with no recurrence for two years)
  4. Subjects with known contraindications to treatment with rituximab
  5. 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
  6. Subjects with a positive ABO crossmatch with donor
  7. 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
  8. 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
  9. Subjects who cannot be followed for the study duration
  10. 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:

  1. All exclusion criteria as at study entry
  2. Positive T- and/or B-cell CDC crossmatch at Day -2
Both
18 Years and older
No
Contact: Paul R Trevillian, MBBS, FRACP +61414417311 Paul.Trevillian@hnehealth.nsw.gov.au
Contact: Solomon Cohney, MBBS, FRACP, PhD +61393427159 Solomon.Cohney@wh.org.au
Australia
 
NCT00371904
RAPTURE
Not Provided
Not Provided
Hunter and New England Health
  • Melbourne Health
  • Princess Alexandra Hospital, Brisbane, Australia
  • Royal Prince Alfred Hospital, Sydney, Australia
  • Auckland City Hospital, New Zealand
  • Monash Medical Centre
  • Royal Perth Hospital
  • Westmead Hospital
  • Royal Adelaide Hospital
Study Chair: Paul R Trevillian, MBBS, FRACP Newcastle Transplant Unit, John Hunter Hospital
Study Chair: Solomon Cohney, MBBS, FRACP, PhD Melbourne Health
Hunter and New England Health
May 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP