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

Phase 2

• Conditions: Kidney Transplantation
• Interventions: Drug: Rituximab; Drug: Standard Care

• Registration Number: NCT00371904
• Lead Sponsor: Hunter and New England Health

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.

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 Timeline

• Study Start: 2006-04
• Study First Submitted: 2006-09-01
• Study First Submitted QC: 2006-09-01
• Study First Posted: 2006-09-04
• Status Verified: 2008-05
• Last Update Submitted: 2008-05-20
• Last Update Posted: 2008-05-21
• Study Completion: 2009-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 192

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Rituximab	-
2	Standard Care	-

Primary Outcome Measures

Name	Time	Method
Biopsy proven antibody mediated rejection	12 months

Secondary Outcome Measures

Name	Time	Method
Death	Month 12
Treated rejection	Month 12
Graft loss	Months 3, 6 and 12
Treatment failure	Months 6 and 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
Calculation of glomerular filtration rate (GFR)	Months 1 - 12
Slope of 1/serum creatinine (Ser. Cr)	Months 6 and 12
24-hour U protein	Months 3 and 12
Safety	Month 12
Cancer and infections	Month 12

Trial Locations

Locations (3)

Monash Medical Centre; 🇦🇺 Clayton, Victoria, Australia

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

Newcastle Transplant Unit, John Hunter Hospital; 🇦🇺 Newcastle, New South Wales, Australia