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

NCT00371904 | Unknown Phase 2

• 1 other identifier: RAPTURE
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 3

Brief 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 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.

Conditions

Kidney Transplantation

Keywords

Rituximab; donor; sensitised; antibody; rejection

Outcome Measures

Primary Outcomes (1)

• Biopsy proven antibody mediated rejection

  12 months

Secondary Outcomes (12)

• Elimination of donor specific antibodies (DSA)

  Day - 2 , 7; Months 1, 3, 6, 9 and 12

• C4d in biopsies

  Day 7; Months 3 and 12

• Plasma exchanges

  Month 12

• Death

  Month 12

• Treated rejection

  Month 12

Study Arms (2)

1

EXPERIMENTAL

Drug: Rituximab

2

ACTIVE COMPARATOR

Drug: Standard Care

Interventions

Rituximab DRUG

Single dose (375 mg/m2) of rituximab to be given intravenously (IV) 14 days prior to transplantation

Also known as: Mabthera

1

Standard Care DRUG

Standard care

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Primary renal transplant lost from acute rejection less than six months prior to randomisation
• 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
• Positive T- and/or B-cell CDC crossmatch at Day -2

Sponsors & Collaborators

• Hunter and New England Health: lead
• Melbourne Health: collaborator
• Princess Alexandra Hospital, Brisbane, Australia: collaborator
• Royal Prince Alfred Hospital, Sydney, Australia: collaborator
• Auckland City Hospital: collaborator
• Monash Medical Centre: collaborator
• Royal Perth Hospital: collaborator
• Westmead Hospital: collaborator
• Royal Adelaide Hospital: collaborator

Study Sites (3)

Newcastle Transplant Unit, John Hunter Hospital

Newcastle, New South Wales, 2305, Australia

RECRUITING

Monash Medical Centre

Clayton, Victoria, 3168, Australia

NOT YET RECRUITING

Royal Melbourne Hospital

Parkville, Victoria, 3052, Australia

NOT YET RECRUITING

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Rituximab; Standard of Care

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Paul R Trevillian, MBBS, FRACP

  Newcastle Transplant Unit, John Hunter Hospital

  STUDY CHAIR

• Solomon Cohney, MBBS, FRACP, PhD

  Melbourne Health

  STUDY CHAIR

Central Study Contacts

Paul R Trevillian, MBBS, FRACP

CONTACT

+61414417311; Paul.Trevillian@hnehealth.nsw.gov.au

Solomon Cohney, MBBS, FRACP, PhD

CONTACT

+61393427159; Solomon.Cohney@wh.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 1, 2006
• First Posted: September 4, 2006
• Study Start: April 1, 2006
• Study Completion: January 1, 2009
• Last Updated: May 21, 2008

Record last verified: 2008-05

Locations

AU (3)