Antibody-mediated kidney transplant rejection Injury, Occupational Diseases, Poisoning
Conditions
Interventions
Patients will be stratified by age and kidney transplant function and randomised at a 1:1 ratio to receive standard of care treatment alone or standard of care plus rituximab. All patients will receiv
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent provided by patient or by a parent or legal guardian for patients aged <16 years 2. Aged 5 years or older 3. Diagnosis of acute antibody-mediated rejection (AMR) as defined by: 3.1. The presence of =1 donor-specific antibodies (DSA) 3.2. An adequate transplant biopsy (=7 glomeruli and =1 artery) with histological features consistent with active AMR with no evidence of chronicity as defined by the Banff histological classification of allograft pathology: 3.2.1. If C4d positive (2 or 3): v score (for arteritis) =1 and/or thrombotic microangiopathy and/or g score (for glomerulitis) =1 and/or ptc score (for peritubular capillaritis) =1, or if co-existing cellular rejection, a g score =1 3.2.2. If C4d negative (0 or 1): microcirculation inflammatory score (g + ptc) =2, or if co-existing cellular rejection, a g score =1 and (g + ptc) =2 plus chronic glomerulopathy (cg) score 0 or 1a, or tubulo-interstitial fibrosis <50% and glomerular obsolescence <50%
Exclusion criteria
Exclusion criteria: 1. ABO-incompatible transplant 2. Received rituximab as part of induction or post-transplant for any other indications within the preceding 12 months (eg. recurrent focal and segmental glomerular sclerosis) 3. Received complete plasma exchange (PEX) treatment prior to the index biopsy on the suspicion of acute AMR in the absence of histology 4. Active infection including bacterial, viral (including CMV and EBV) or fungal infection or tuberculosis, which in the investigator’s opinion could affect the conduct of the study 5. Co-existing BK nephropathy 6. Active hepatitis B or hepatitis C (patients with prior exposure to hepatitis B may be enrolled at the discretion of the PI; patients may be included if a negative hepatitis C recombinant immunoblot assay is confirmed or have a negative hepatitis C virus RNA [qualitative] test), or subjects with suspected human immunodeficiency virus (HIV) infection 7. Active malignancy 8. Known allergy, intolerance or contraindication to the treatments in the standard of care arm or rituximab as outlined in the Summaries of Product Characteristics (SmPCs) 9. Clinically significant comorbidity 10. Females must be either post-menopausal for at least 1 year, surgically sterile or, if of child-bearing potential, must not be pregnant or lactating. If sexually active, must agree to use an acceptable method of birth control for the first year post-randomisation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Allograft survival, defined as the duration from the date of randomisation to the date of starting dialysis dependency or date of eGFR <15 mL/min/1.73 m2, with follow-up of 48 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Serum creatinine ) at 1, 3, 6, and 12 months post-randomisation and then annually until 4 years 2. Estimated GFR (CKD-EPI) ) at 1, 3, 6, and 12 months post-randomisation and then annually until 4 years 3. Proteinuria (urinary protein:creatinine ratio) ) at 1, 3, 6, and 12 months post-randomisation and then annually until 4 years 4. Donor-specific antibody (DSA) positivity at 3 and 12 months 5. Number of different DSA at at 3 and 12 months 6. Level of the immunodominant DSA assessed using mean fluorescence index at 3 and 12 months 7. Adverse event rate assessed by reviewing patient medical records 8. Patient-reported health-related quality of life , assessed using EQ-5D-5L/EQ-5D-Y questionnaires at baseline, 3 months, and 1, 2, 3 and 4 years following transplantation 9. Economic analysis of cost per quality-adjusted life year (QALY) gained from the perspective of the NHS | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Contacts
Public ContactGraham Armstrong
Outcome results
None listed