Renal Transplant recipients with HLA antibodies, who are at increased risk of graft dysfunction and graft failure MedDRA version: 14.1 Level: LLT Classification code 10050436 Term: Prophylaxis against renal transplant rejection System Organ Class: 100000004865
Conditions
Interventions
Product Name: Prednisolone
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisolone
CAS Number: 50-24-8
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 1-5
Pr
Sponsors
Kings College London
Guy's and St Thomas' Foundation NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Written and witnessed informed consent to participate. • Renal transplant recipients >1 year post-transplantation, male or female • Aged 18-70 years • Estimated glomerular filtration rate (eGFR by 4 variable MDRD) of =30. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3000 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3000
Exclusion criteria
Exclusion criteria: • Recipient requiring HLA desensitisation to remove antibody for a positive XM transplant • Recipient known already to have HLA antibody WHO HAS RECEIVED specific intervention for that antibody or for CAMR / chronic rejection • Recipient of additional solid organ transplants (e.g. pancreas, heart, etc). • History of malignancy in previous 5 years (excluding non-melanomatous tumours limited to skin) • HBsAg+,HBcAb+, HepC+ or HIV+ recipient (on test performed within previous 5 years) • History of acute rejection requiring escalation of immunosuppression in the 6 months prior to screening. • Patient enrolled in any other studies involving administration of another IMP at time of recruitment The following exclusion criteria are based on information contained within the SMPcs of the IMPs • History of an ongoing or previous infection (no time limit) that would prevent optimization of immunosuppression, including ocular Herpes simplex. • Known hypersensitivity to any of the IMPs • Known hereditary disorders of carbohydrate metabolism • Pregnancy or breastfeeding females (based on verbal history of recipient) • Pre-menopausal females who refuse to consent to using suitable methods of contraception throughout the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the 3-year graft failure rate in patients testing positive for HLA Ab at baseline or within 3 years of randomization who receive an optimized anti-rejection medication intervention with prednisone, Tac and MMF (‘treatment’), compared to a control group who test positive for HLA Ab at baseline or within 3 years post-randomization who remain on their established immunotherapy and whose clinicians are not aware of their Ab status. ;Secondary Objective: Determine the 3-year graft failure rate in patients randomized to unblinded HLA Ab screening, compared to a control group randomized to blinded LA Ab screening. Determine whether ‘treatment’ influences patient survival Determine whether ‘treatment’ influences the development of graft dysfunction (assessed by presence of /change in eGFR) Determine whether ‘treatment’ influences the rates of acute rejection in these groups Determine the adverse effect profiles of ‘treatment’ in this group, Determine the cost effectiveness of routine screening for HLA Ab and prolonging transplant survival using this protocol. Determine the impact of biomarker screening and “treatment” on the patients’ adherence to drug therapy and their perceptions of risk to thetransplant health Collect regular samples from patients enrolled to HLA Ab+ groups to develop more sophisticated biomarkers of progression and/or responsiveness to therapy ;Primary end point(s): 3-year graft failure rates in HLA Ab positive patients randomized to biomarker-led treatment groups vs. 3-year graft failure rates in HLA Ab positive patients randomized to the control (standard care) group. Graft failure will be defined as re-starting dialysis or requiring a new transplant.;Timepoint(s) of evaluation of this end point: 3 years post-recruitment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical: • 3 year graft failure rates in patients randomized to unblinded HLA Ab screening vs. blinded screening • patient survival. • rate of progression of graft dysfunction, as assessed by presence of proteinuria (Protein Creatinine Ratio >50) or change in estimated Glomerular Filtration Rates over 3 years. • rates of biopsy-proven T cell-mediated or antibody-mediated rejection over 3 years. • rates of culture-positive infection, biopsy-proven malignancy and diabetes mellitus. • health economic analysis of outcomes in intervention vs. control groups. • analysis of adherence and perceptions of risk in biomarker led care vs standard care groups Scientific: • changes in HLA Ab levels or specificity. • changes in laboratory parameters of T & B cell phenotype and responsiveness. • change in numbers and phenotype of circulating CD34+ cells. ;Timepoint(s) of evaluation of this end point: All evaluated at 3 years post-recruitment | — |
Countries
United Kingdom
Contacts
Public ContactAnthony Dorling
Kings College London & Guy’s and St Thomas’ NHS Foundation Trust
Outcome results
None listed