Drug Induced Liver Injury
Conditions
Keywords
Drug induced liver injury, liver failure, glucocorticoids, clinical trial, Hyperbilirubinemia
Brief summary
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.
Detailed description
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.
Interventions
DRUGMethylprednisolone
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
DRUGGlutathione
It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 1.2g to 1.8g
DRUGSilymarin
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.
PROCEDUREPlaslna exchange
It is suitable for patients whose condition continues to worsen or even develop to liver failure.
PROCEDURELiver transplantation
It is suitable for patients whose condition continues to worsen or even develop to liver failure.
Sponsors
General Hospital of Shenyang Military Region
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* A definite diagnosis of acute DILI; * 5×ULN ≤ TBIL level at baseline ≤ 20×ULN; * Age 18-80 years old; * Sign the informed consent form.
Exclusion criteria
* Other causes of liver injury, including viral hepatitis, cytomegalovirus infection, Epstein-Barr virus infection, Herpes virus infection, autoimmune liver disease, alcoholic liver disease, hypoxic/ischemic liver disease, Budd-Chiari syndrome, biliary tract disease, Wilson's disease, hemochromatosis, and α1-antitrypsin deficiency; * Immune checkpoint inhibitors or gynura segetum induced DILI; * Absolute contraindications to glucocorticoids, such as systemic mold infections or allergies; * A history of glucocorticoid therapy within 3 months before enrollment; * A history of diseases requiring glucocorticoid maintenance therapy, such as rheumatoid arthritis, systemic lupus erythematosus, systemic dermatomyositis, etc; * A history of liver transplantation; * Received artificial liver therapy before enrollment; * Malignant tumor of the liver, bile duct, pancreas or liver metastasis * Acute liver failure; * Renal dysfunction, creatinine Cr≥133μmol/L; * Neutrophil count \<1,000,000,000/L; * Active tuberculosis; * Severe cardiopulmonary diseases; * Recent surgery or trauma; * Mental illness; * Pregnancy or lactation; * Participated in other clinical studies within 3 months before enrollment; * Other conditions judged by the clinician to be inappropriate for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of DILI on the second week | 2 weeks | TBIL level decreases by 50% as compared to the baseline level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of DILI on the fourth week | 4 weeks | TBIL level decreases by 50% as compared to the baseline level. |
| Progressive liver injury on the second week | 2 weeks | TBIL level increases as compared to the baseline level. |
| Progressive liver injury on the fourth week | 4 weeks | TBIL level increases as compared to the baseline level. |
| Improvement of liver enzymes on the second week | 2 weeks | Proportion of 50% reduction from baseline in ALT, AST, ALP, and GGT levels. |
| Improvement of liver enzymes on the fourth week | 4 weeks | Proportion of 50% reduction from baseline in ALT, AST, ALP, and GGT levels. |
| Survival | 3 months | All participants will be followed by telephone to record survival status, including the major cause and date of death. |
| Adverse events | 3 months | 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. |
| Liver failure | 3 months | Participants develop overt hepatic encephalopathy with an INR of ≥1.5. |
| Liver transplantation | 3 months | Participants undergo liver transplantation due to liver failure. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Population who will be more suitable for glucocorticoids treatment | 3 months | Characteristics of patients with DILI in whom glucocorticoids treatment is more beneficial. |
| Changes of inflammatory factors | 4 weeks | Changes of IL-6 and TNF-α levels. |
Countries
China
Contacts
Primary ContactXingshun Qi
Backup ContactQianqian Li
Outcome results
None listed