Extended Release Versus Immediate Release Tacrolimus Following Renal Allograft Failure to Reduce Allosensitisation

Study Overview
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Brief Summary
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Study to compare once-daily extended release tacrolimus versus twice-daily immediate release tacrolimus following renal allograft failure to reduce the risk of allosensitisation

Official Title
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Study to Compare Once-daily Extended Release Tacrolimus Versus Twice-daily Immediate Release Tacrolimus Following Renal Allograft Failure to Reduce the Risk of Allosensitisation

Conditions
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Kidney Transplant Failure, Allosensitization, Immunosuppression

Intervention / Treatment
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* Drug: Envarsus Oral Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to give informed consent. Male or female, at least 18 years of age. Has renal allograft failure and is due to start haemodialysis therapy or within 28 days following starting dialysis. Has been already activated on the transplant wait list or is undergoing work up to be reactivated on the transplant list. Has no indication for graft nephrectomy at the time of transplant failure. Is receiving an immediate release tacrolimus maintenance immunotherapy regimen at the time of allograft failure. Exclusion Criteria: Has another functioning organ transplanted (eg. pancreas, liver, cardiac) at the time of kidney allograft failure. Allograft failure within a month of transplant. Patients who are due to receive or receiving peritoneal dialysis following graft failure. Patients with detectable DSA at the time of allograft failure Receiving an extended release preparation of tacrolimus as immunotherapy at the time of graft failure. Requires continuation of maintenance immunosuppression other than prednisolone or tacrolimus (eg. Mycophenolate mofetil or sirolimus). Patients who on IR-FK conversion would require less than 0.75mg of Envarsus. HLA type of donor is unknown. Has a history of, or active co-morbidity that in the Investigator's opinion, could affect the conduct of the study. 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 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. Has active malignancy. Female patients of child bearing age, who wish to consider pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Immediate release tacrolimus<br>Patients will continue on immediate release tacrolimus | |
| Active Comparator: Extended release tacrolimus<br> | Drug: Envarsus Oral Product<br>* Patients will be randomised to receive either envarsus or to continue on an immediate release tacrolimus formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of de novo allosensitisation (donor specific antibodies) at 24 months post allograft failure. | Number of patients who develop new DSA in each group | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication adherence measurement | Will be measured by BAASIS questionnaire (comparison of scores) | 24 months | 
| Health-Related Quality of Life measurement | Will be measured by the EQ-5D-5L Questionnaire (comparison of scores) - 5D - 5L Questionnaire | 24 months | 
| Coefficient of variation of tacrolimus levels at 24 months post allograft failure. | Incorporating all study visit trough tacrolimus levels (standard deviation/mean) | 24 months | 
| Adverse events | Incidence of infective episodes, malignancy, diabetes, erythropoietin resistance, graft nephrectomy | 24 months | 
| Chances of re-transplantation as determined by the transplant matchability calculator available from NHSBT | Will be calculated by using the NHSBT calculator | 24 months | 
| Proportion of patients retransplanted during the study period | Proportion of patients in each arm receiving a transplant | 24 months |