Feasibility, Efficacy And Safety Of De Novo Extended-Release Tacrolimus Following Liver Transplantation
Trial Snapshot
- Phase
- Phase 4
- Status
- Recruiting
- Sponsor
- University of Alberta
- Enrollment
- 94
- Locations
- 2
- Primary Endpoint
- Safety of Envarsus as indicated by adverse events
Study Overview
Brief Summary
Medications used after transplant to prevent rejection are associated with many side effects. Tacrolimus side effects include kidney dysfunction; tremor, headaches, difficulty sleeping, change in sensation (legs), seizure, or confusion; high blood pressure; anemia, or low blood cell counts; diabetes; abnormal cholesterol and weight gain. The investigators want to use a new, approved, formulation of the standard medication (Envarsus) as they believe it may be associated with reduced side effects. The investigators would like to assess how safe it is to use this medication and how well it works in comparison to currently used formulations. The investigators will study if there are less side effects and will study clinical outcomes (including how well the liver does and if there is need for hospitalizations after transplant).
The investigators hope that this information will improve the care provided to and outcomes in patients following liver transplant.
Detailed Description
PURPOSE
To assess the impact of Envarsus on toxicity and clinical outcomes in participants following liver transplant. Tacrolimus-based immunosuppression is the standard of care following liver transplantation (LT). This medication is associated with significant toxicity including renal dysfunction, increased risk of diabetes and neurotoxicity. Of note, both nephrotoxicity and neurotoxicity occur at elevated peak serum tacrolimus blood concentrations and improve when the dose is reduced or discontinued. Envarsus does not have the high peak seen with initial dosing in the other formulations. This may be one of the reasons Envarsus use improves tremor associated with tacrolimus use.
HYPOTHESES
Use of extended-release tacrolimus following LT will be: 1. Effective and safe. 2. Without any difference in rejection. 3. Less nephrotoxic with reduced incidence of renal impairment. 4. Better with regard to features of metabolic syndrome including myosteatosis. 5. Less neurotoxic. 6. Better with regard to both graft and patient survival when compared to immediate-release tacrolimus (Prograf®).
JUSTIFICATION
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •- Adult individuals transplanted at the University of Alberta
Exclusion Criteria
- •Individuals with congenital long QT syndrome
- •Patients with elevated bilirubin > 100 umol/L post-LT (at day 3)
- •Patients with chronic kidney disease (eGFR < 45 ml per minute per 1.73 m2)
- •Patients with acute kidney injury requiring discontinuation of calcineurin inhibitors.
- •Patients who have hepatocellular carcinoma, require a re-transplant, or receive multi-visceral transplant
Arms & Interventions
Prograf (SOC)
Prograf tablet Dose 0.10 - 0.15mg/Kg daily Frequency: 2 doses per day (dose above split in half for each dose)
Intervention: Prograf (SOC) (Drug)
Envarsus
Envarsus tablet Dose 0.11 - 0.13 mg/Kg/day Frequency: once per day
Intervention: Envarsus Oral Product (Drug)
Outcomes
Primary Outcomes
Safety of Envarsus as indicated by adverse events
Time Frame: 1 year
Adverse events include frequency of transplant rejection, and changes from baseline in clinical laboratory parameters
Secondary Outcomes
- Number of patients with metabolic syndromes [diabetes](1-10 years)
- Patient Survival(1-10 years)
- Graft Survival(1-10 years)
- Muscularity assessment(1 year)
- Impact on quality of life (QOL) - EuroQuol Visual Analogue Scale (VAS)(1 year)
- Incidence of renal impairment(1-10 years)
- Incidence of neurotoxicity(1 years)
- Length of stay in hospitalized patients(1-10 years)
- Incidence of Intensive Care Unit (ICU) admission(1-10 years)
- Length of Intensive Care Unit admission(1-10 years)
- Incidence of hospitalizations(1-10 years)
- Impact on quality of life (QOL) - Chronic Liver Disease Questionnaire(1 year)
- Impact on quality of life (QOL) - EuroQuol-5Dimensions-5 Levels Questionnaire(1 year)