Glucocorticoids for Acute Drug Induced Liver Injury With Hyperbilirubinemia

Not Applicable

Not yet recruiting

• Conditions: Drug Induced Liver Injury
• Interventions: Drug: Methylprednisolone; Drug: Magnesium isoglycyrrhizinate; Drug: Glutathione; Drug: Silymarin; Drug: Polyene Phosphatidylcholine; Drug: Ursodeoxycholic acid capsules; Drug: Ademetionine 1,4-Butanedisulfonate; Procedure: Plaslna exchange; Procedure: Liver transplantation

• Registration Number: NCT06922669
• Lead Sponsor: General Hospital of Shenyang Military Region

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.

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2025-04-03
• Study First Submitted QC: 2025-04-03
• Last Update Submitted: 2025-04-03
• Study First Posted: 2025-04-10
• Last Update Posted: 2025-04-10
• Study Start: 2025-06-01
• Primary Completion: 2027-03-31
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 232

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Glucocorticoids group	Methylprednisolone	Glucocorticoids step-down therapy combined with conventional treatment.
Glucocorticoids group	Magnesium isoglycyrrhizinate	Glucocorticoids step-down therapy combined with conventional treatment.
Glucocorticoids group	Glutathione	Glucocorticoids step-down therapy combined with conventional treatment.
Glucocorticoids group	Silymarin	Glucocorticoids step-down therapy combined with conventional treatment.
Glucocorticoids group	Polyene Phosphatidylcholine	Glucocorticoids step-down therapy combined with conventional treatment.
Glucocorticoids group	Ursodeoxycholic acid capsules	Glucocorticoids step-down therapy combined with conventional treatment.
Glucocorticoids group	Ademetionine 1,4-Butanedisulfonate	Glucocorticoids step-down therapy combined with conventional treatment.
Glucocorticoids group	Plaslna exchange	Glucocorticoids step-down therapy combined with conventional treatment.
Glucocorticoids group	Liver transplantation	Glucocorticoids step-down therapy combined with conventional treatment.
Conventional treatment	Magnesium isoglycyrrhizinate	Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI.
Conventional treatment	Glutathione	Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI.
Conventional treatment	Silymarin	Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI.
Conventional treatment	Polyene Phosphatidylcholine	Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI.
Conventional treatment	Ursodeoxycholic acid capsules	Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI.
Conventional treatment	Ademetionine 1,4-Butanedisulfonate	Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI.
Conventional treatment	Plaslna exchange	Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI.
Conventional treatment	Liver transplantation	Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI.

Primary Outcome Measures

Name	Time	Method
Improvement of DILI on the second week	2 weeks	TBIL level decreases by 50% as compared to the baseline level.

Secondary Outcome Measures

Name	Time	Method
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.
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.
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.

Trial Locations

Locations (1)

Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area); 🇨🇳 Shenyang, Liaoning, China