Budesonide versus prednisolone after liver transplantation: a phase 3, open label, non-inferiority randomised controlled trial
Austin Health
100 participants
Aug 14, 2023
Interventional
Conditions
Summary
This study will investigate whether a drug called budesonide is tolerable and as effective as the standard drug prednisolone in reducing the immune system to prevent organ rejection following liver transplantation. Enrolled participants will be randomly placed into two groups. In the control group, participants will be given standard immunosuppression with prednisolone following their liver transplant. In the intervention group, participants will be given budesonide instead of prednisolone. We will compare rates of organ rejection and differences in infectious, metabolic, musculoskeletal, endocrine and psychological complications between the two groups. We predict budesonide will be comparable to prednisolone in preventing organ rejection following liver transplantation, whilst resulting in fewer side effects.
Eligibility
Inclusion Criteria1
- All adult (age 18 years or over) patients accepted for liver transplantation at Austin Health.
Exclusion Criteria9
- Strong medical rationale for a corticosteroid-free protocol (e.g. severe psychiatric comorbidities, high risk of infection) as determined by the Liver Transplant Multidisciplinary Team
- Patient with autoimmune hepatitis
- Corticosteroid dependency prior to trial enrolment
- Patients receiving multi-visceral organ transplantation
- Previous liver transplant recipient requiring redo liver transplant
- Portosystemic shunt >15mm in diameter on imaging which will reduce budesonide first pass metabolism
- Concurrent use of medications that are significant cytochrome P450 3A4 inhibitors (e.g. erythromycin, clarithromycin, verapamil, diltiazem) which will reduce budesonide first pass metabolism
- Unable to take medications enterally (either orally or through tube feeding) by day 3 post liver transplant
- Patients unable to understand written English sufficiently to read PICF or have no carer to assist them with adequate understanding of PICF
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Interventions
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.
Locations(1)
View Full Details on ANZCTR
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ACTRN12623000340639