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

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

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

Study Overview

• Status: Recruiting
• Conditions: Immunosuppression; Kidney Transplant Failure; Allosensitization
• Intervention / Treatment: Drug: Envarsus Oral Product

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Imperial College Healthcare NHS Trust
    • Contact: Michelle Willicombe; Phone Number: 02083836641; Email: imperial.evitra.study@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 list.
5. Has no indication for graft nephrectomy at the time of transplant failure.
6. Is receiving an immediate release tacrolimus maintenance immunotherapy regimen at the time of allograft failure.

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 transplant.
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 is 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: September 20, 2018
• First Submitted That Met QC Criteria: September 24, 2018
• First Posted (Actual): September 28, 2018

Study Record Updates

• Last Update Posted (Actual): February 28, 2019
• Last Update Submitted That Met QC Criteria: February 27, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 18IC4423

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No