Does rituximab added to usual treatment reduce kidney transplant failure following rejection?

Phase 3

• Conditions: Antibody-mediated kidney transplant rejection; Injury, Occupational Diseases, Poisoning

• Registration Number: ISRCTN18179652
• Lead Sponsor: Imperial College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-11
• Last Update Posted: 26 September 2023
• Study Completion: 2026-02-01

Recruitment & Eligibility

• Status: Stopped
• Sex: All
• Target Recruitment: 170

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

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.