Renal transplant immunosuppression Urological and Genital Diseases Renal transplant immunosuppression
Conditions
Interventions
Comparing two immunosuppression regimes:
1. Control (standard regime) - intra-operative Basiliximab and steroids followed by maintenance with Tacrolimus and MMF
2. Steroids intra-operative followed by
Sponsors
Leeds Teaching Hospitals NHS Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients who must be over age 18 years 2. Patients must be recipients of heart-beating cadaveric, non-heart beating or living donors 3. Patients receiving a 2nd or subsequent grafts must have maintained their primary graft for a minimum of 6 months, except if graft failure was due to technical reasons 4. Written informed consent 5. Women at risk of pregnancy must have a negative pregnancy test before commencing the trial and agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuing the trial. The manufacturer of Alemtuzumab advises effective contraception for 6 months after administration to men or women. Advice will be given to patients to discuss with the transplant medical staff if a pregnancy is planned.
Exclusion criteria
Exclusion criteria: 1. Regional patients from Hull Royal Infirmary (due to the logistical difficulties in following these patients up from Leeds) 2. High Risk Recipients - defined as recipients who have one or more of the following: 2 human leukocyte antigen, type DR (HLA-DR) mismatch, previous immunologically mediated graft loss in less than 6 months, preoperative donor specific antibodies 3. Known hypersensitivity to the investigational medicinal product (IMP) including the standard drugs 4. Prohibited prior or concomitant medications 5. Pregnant women or nursing mothers 6. White blood cell count (WBC) count <3000/mm^3 or platelets <75,000/mm^3 at time of study entry 7. Any other concurrent cardiovascular, gastrointestinal, pulmonary or haematological conditions that would restrict the administration of study drugs in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Diethylene triamine pentaacetate (DTPA) isotopic glomerular filtration rate (GFR) at 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Patient and graft survival 2. Incidence and duration of delayed graft function 3. Incidence and severity of steroid-treated presumptive and biopsy-confirmed acute rejection 4. Comparison of blood pressure control between groups by clinic readings, number of agents used and 24 hour monitoring at 6 and 12 months 5. Comparison of groups by pulse wave analysis, a powerful surrogate marker for cardiovascular outcome, at baseline, 6 and 12 months 6. Incidence of impaired glucose tolerance, weight gain and diabetes at 6 weeks, 6 and 12 months 7. Assessment of quality of life by questionnaires at 6 and 12 months 8. Assessment of adherence, looking at trough tacrolimus level variations between two groups 9. Economic analysis of the cost-effectiveness of both regimes 10. Comprehensive assessment of clinically indicated, implantation and one year protocol biopsies by: 10.1. Morphological scoring by Banff/chronic allograft damage index (CADI) system 10.2. Assessment of fibrosis by specific stains 10.3. Genomic analysis for products associated with ischaemia reperfusion, immune activation, inflammation and fibrosis 11. Analysis of urine and blood by proteomics at baseline, 3 months, 6 months, 12 months and other clinically indicated time points 12. Analysis of T cells for development of regulatory T cells 13. Analysis of anti-donor antibody responses 14. Monitoring of B and T cell subsets by flow cytometry 15. Monitoring of infectious complications/pathogens - including cytomegalovirus (CMV) infection and infections with polyomaviruses 16. Incidence of post transplant malignancies including post-transplant lymphoproliferative disease (PTLD) 17. Biochemical and haematological monitoring | — |
Countries
United Kingdom
Outcome results
None listed