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.
None
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.
Parallel
Envarsus Oral Product
Drugas described in arm/group description
Prograf (SOC)
DrugPrograf (SOC)
Safety of Envarsus as indicated by adverse events
Adverse events include frequency of transplant rejection, and changes from baseline in clinical laboratory parameters
Incidence of renal impairment
We will consider participants with \>10% decline in GFR to represent a group with renal impairment. We will define acute kidney injury (AKI) as at least a 50% and/or a 26.5 µmol/L (0.3 mg/dL) increase in serum creatinine level relative to the baseline reference value as per Kidney Disease: Improving Global Outcomes (KDIGO) criteria (11) in participants without pre-existing CKD. CKD will be defined as eGFR \<60 ml/min for more than 3 months, according to the KDIGO criteria (13), evidence of intrinsic renal disease or requiring renal replacement therapy. Acute on CKD will be defined as at least a 50% and/or a 26.5 µmol/L (0.3 mg/dL) increase in serum creatinine level relative to the baseline reference value as per KDIGO criteria (11) in participants with pre-existing CKD. The baseline creatinine will be defined as the minimum of all values available within 3 months of LT.
Number of patients with metabolic syndromes [diabetes]
Diabetes will be diagnosed based on an elevated fasting plasma glucose (≥7.0 mmol/l) or an elevated 2-hour plasma glucose (≥11.1 mmol/l) during an oral glucose tolerance test or an elevated random plasma glucose (≥11.1 mmol/l). Glycemic control will be measured by fasting blood glucose and hemoglobin A1C (at 3-, 6-, 12, 60-months following LT and at end of follow up). Change in hemoglobin A1C at 1 year post LT from baseline will be used as a measure of glycemic control. Hemoglobin A1C value within 3 months of LT will be used as the baseline value.
Incidence of neurotoxicity
adverse events including tremor, headache, insomnia, dysesthesia, or mood disturbance will be recorded. Severe events including akinetic mutism, seizures, cortical blindness, focal neurological deficits, encephalopathy, decreased cognitive ability and psychosis will be monitored and recorded
Length of stay in hospitalized patients
From time of admission for surgery to time of discharge.
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