Glucocorticoids for Acute Drug Induced Liver Injury With Hyperbilirubinemia

General Hospital of Northern Theater Command of Chinese People's Liberation Army

Status: Enrolling

Conditions: Drug Induced Liver Injury

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06922669

XHNKKY-ASDILI-RCT

Details and patient eligibility

About

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.

Full 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.

Enrollment: 232 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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232 participants in 2 patient groups

Glucocorticoids group

Experimental group

Description:

Glucocorticoids step-down therapy combined with conventional treatment.

Treatment:

Drug: Magnesium isoglycyrrhizinate

Drug: Ursodeoxycholic acid capsules

Procedure: Liver transplantation

Drug: Glutathione

Drug: Silymarin

Drug: Methylprednisolone

Procedure: Plaslna exchange

Drug: Polyene Phosphatidylcholine

Drug: Ademetionine 1,4-Butanedisulfonate

Conventional treatment

Active Comparator group

Description:

Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI.

Treatment:

Drug: Magnesium isoglycyrrhizinate

Drug: Ursodeoxycholic acid capsules

Procedure: Liver transplantation

Drug: Glutathione

Drug: Silymarin

Procedure: Plaslna exchange

Drug: Polyene Phosphatidylcholine

Drug: Ademetionine 1,4-Butanedisulfonate