Budesonide versus prednisolone after liver transplantation: a phase 3, open label, non-inferiority randomised controlled trial

Intervention ('Budesonide Arm'): oral tablet budesonide 9mg daily between day 3 to day 14 post liver transplantation, weaned to oral tablet budesonide 6mg daily at week 3 post liver transplantation, then oral budesonide 3mg daily at week 5 post liver transplantation and then ceased at end of week 6 post liver transplantation. After the 6 week course of budesonide, patients will return any leftover medication to the Clinical Trials Pharmacy for counting and assessment of adherence. Patients in both the Control Arm and the Budesonide Arm will receive a single dose of intravenous methylprednisolone intra-operatively followed by intravenous methylprednisolone 16mg daily on days 1 and 2 following liver transplantation. Other concomitant immunosuppression will be continued in both the Control and Budesonide Arms based on stratification by renal function, as per standard of care. Patients with impaired renal function (e.g. creatinine >120mg/dL or hepatorenal syndrome requiring terlipressin) will receive intravenous basiliximab 20mg on days 1 and 4 following liver transplant, and then receive oral tablet tacrolimus twice daily with dose titrated to drug trough levels. Patients with normal renal function will receive oral tablet tacrolimus twice daily with dose titrated to drug trough levels. All patients will receive mycophenolate mofetil 1g twice daily, except for patients with primary sclerosing cholangitis as the underlying aetiology of liver disease, who received weight-based azathioprine (typically azathioprine 100mg daily). Medications will be administered intravenously until the patient is able to tolerate oral intake.