Transplant rejection following transplant failure and return to dialysis (transplant rejection defined as the development of new HLA antibodies against the transplant) MedDRA version: 20.0 Level: LLT Classification code 10050436 Term: Prophylaxis against renal transplant rejection System Organ Class: 100000004865
Conditions
Interventions
Trade Name: Envarsus
Product Name: Envarsus
Pharmaceutical Form: Tablet
INN or Proposed INN: tacrolimus
CAS Number: 109581-93-3
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to give informed consent. 2. Male or female, at least 18 years of age. 3. Has renal allograft failure and is due to start haemodialysis therapy, or within 28 days following starting dialysis. 4. Has been already activated on the transplant wait list or is undergoing work up to be reactivated on the transplant live. 5. Has no indication at the time of transplant failure for graft nephrectomy. 6. Is receiving an immediate release tacrolimus maintenance immunotherapy regimen at the time of allograft failure. 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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: 1. Has another functioning organ transplanted (eg. pancreas, liver, cardiac) at the time of kidney allograft failure. 2. Allograft failure within a month of transplantation. 3. Patients who are due to receive or receiving peritoneal dialysis following graft failure. 4. Patients with detectable DSA at the time of allograft failure 5. Receiving an extended release preparation of tacrolimus as immunotherapy at the time of graft failure. 6. Requires continuation of maintenance immunosuppression other than prednisolone or tacrolimus (eg. Mycophenolate mofetil or sirolimus). 7. Patients who on IR-FK conversion would require less than 0.75mg of Envarsus. 8. HLA type of donor unknown. 9. Has a history of, or active co-morbidity that in the Investigator’s opinion, could affect the conduct of the study. 10. Has any condition at the time of recruitment which would prohibit or pose a relative contraindication for the continued use of tacrolimus to a target trough level of between 3-5ng/ml 11. Active bacterial, viral (including CMV and EBV) or parasitic infections, including tuberculosis that, in the Investigator’s opinion, could affect the conduct of the study. 12. Has active malignancy. 13. Female patients of child bearing age, who wish to consider pregnancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Does taking a preparation of a once-daily, slow release anti-rejection tablet (tacrolimus), compared with a twice-daily, immediate release anti-rejection tablet (tacrolimus) effect the incidence of new HLA antibodies (antibodies against another person's tissue/cells) in patients with failed kidney transplants who are on dialysis and are awaiting a further transplant. ; Secondary Objective: The hypothesis is that once-daily slow release tacrolimus may improve adherence and a higher proportion of 'target' drug (tacrolimus) blood levels than patients receiving immediate release tacrolimus. This in turn will be reflecting in the degree of new HLA antibodies detected in the participants. Adherence will be monitored using questionnaires in combination with drug (tacrolimus) levels. Quality of life measurements will also be assessed, to better assess the impact of return to dialysis in this population. The chances of re-transplantation will also be assessed using the data on new HLA antibody development in each group. This can be determined by using a calculator developed by NHS Blood and Transplant, who are responsible for transplant allocation. ;Primary end point(s): The rate of de novo HLA antibodies (or donor specific antibodies) developed at 24 months post recruitment.; Timepoint(s) of evaluation of this end point: The primary end point will be measured at 24 months post transplant failure. Routinely patients have their HLA antibodies measured every 3 months whilst on the transplant wait list. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The questionnaires will be performed at 3 months, 6 months and then 6 monthly intervals until the end of the trial at 2 years Tacrolimus levels will be monitored every 3 months Clinical assessments will be made every 3 months as part of routine care (de novo malignancies etc) The end of retransplantability will only be performed with the results of the final HLA antibody screen ; Secondary end point(s): 1. Adherence measurement (measured by a modified BAASIS questionnaire) 2. QOL measurement (measured by the EQ-5D Health-Related Quality of Life Questionnaire) 3. Coefficient of variation of tacrolimus levels at 24 months post allograft failure. 4. Proportion of trough tacrolimus levels <3.0ng/ml. 5. Incidence of infection episodes. 6. Incidence of de novo malignancies. 7. Rates of diabetes development (defined as the requirement of hypoglycaemic agents). 8. Incidence of erythropoietin resistance (defined as failure to achieve or maintain haemoglobin levels within the desired target range despite appropriate ESA doses per kg of body weight). 9. Requirement for clinically indicated allograft nephrectomy. 10. Chances of re-transplantation as determined by the transplant matchability calculator available from NHSBT. 11. Proportion of patients retransplanted during the study period. | — |
Countries
United Kingdom
Contacts
Public ContactPereira Barreto
Imperial College London
Outcome results
None listed