Drug-induced liver injury (DILI) can lead to potentially fatal complications, such as acute liver failure and even death. In clinical practice, glucocorticoids have been considered in some cases of DILI, especially patients with hyperbilirubinemia. However, the available evidence remains controversial and its quality is also very limited. Herein, a multicenter randomized controlled trial (RCT) has been designed to explore the efficacy and safety of glucocorticoids in patients with acute DILI and hyperbilirubinemia.
Overall, 232 patients with acute DILI with hyperbilirubinemia will be enrolled. They will be randomly assigned at a ratio of 1:1 to the conventional treatment alone or combined with glucocorticoids groups. The primary endpoint is the improvement of DILI after treatment on second week. Secondary endpoints include the improvement of DILI on fourth week, rates of progressive liver injury, liver failure, liver transplantation, survival, and adverse events. Exploratory endpoints will assess the beneficial population and changes of inflammatory factors following glucocorticoid treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
232
Initially, an intravenous dose of 1 mg/kg/day of methylprednisolone will be administered for one week, with the possibility of extending treatment to two weeks if necessary. Following this, participants will receive oral methylprednisolone tablets, starting at a dose of 40 mg/day. The oral dosage will be gradually tapered based on the participants' condition over a period of 1 to 3 months.
It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 0.15g to 0.2g
It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 1.2g to 1.8g
It is suitable for patients with hepatocellular or mixed DILI. The dosage is 140 mg, taken 2 to 3 times per day.
It is suitable for patients with hepatocellular or mixed DILI. The dosage is 228mg-456mg, taken 3 times per day.
It is suitable for patients with cholestatic or mixed DILI. A daily dose of 10mg-15mg/kg/day.
It is suitable for patients with cholestatic or mixed DILI. A daily dose of 0.5g to 1g.
It is suitable for patients whose condition continues to worsen or even develop to liver failure.
It is suitable for patients whose condition continues to worsen or even develop to liver failure.
Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area)
Shenyang, Liaoning, China
RECRUITINGImprovement of DILI on the second week
TBIL level decreases by 50% as compared to the baseline level.
Time frame: 2 weeks
Improvement of DILI on the fourth week
TBIL level decreases by 50% as compared to the baseline level.
Time frame: 4 weeks
Progressive liver injury on the second week
TBIL level increases as compared to the baseline level.
Time frame: 2 weeks
Progressive liver injury on the fourth week
TBIL level increases as compared to the baseline level.
Time frame: 4 weeks
Improvement of liver enzymes on the second week
Proportion of 50% reduction from baseline in ALT, AST, ALP, and GGT levels.
Time frame: 2 weeks
Improvement of liver enzymes on the fourth week
Proportion of 50% reduction from baseline in ALT, AST, ALP, and GGT levels.
Time frame: 4 weeks
Liver failure
Participants develop overt hepatic encephalopathy with an INR of ≥1.5.
Time frame: 3 months
Liver transplantation
Participants undergo liver transplantation due to liver failure.
Time frame: 3 months
Survival
All participants will be followed by telephone to record survival status, including the major cause and date of death.
Time frame: 3 months
Adverse events
Adverse events related to glucocorticoids mainly include infection, water-sodium retention, Cushing syndrome, poor glycemic, gastrointestinal ulcer, thromboembolic disease, neuropsychiatric symptoms, osteoporosis, increased intraocular pressure, and withdrawal syndrome. They will be closely recorded during the period of glucocorticoids treatment.
Time frame: 3 months
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