Glucocorticoids for Acute Drug Induced Liver Injury With Hyperbilirubinemia

NCT06922669 | Recruiting

• 1 other identifier: XHNKKY-ASDILI-RCT
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Induced Liver Injury

Keywords

Drug induced liver injury; liver failure; glucocorticoids; clinical trial; Hyperbilirubinemia

Outcome Measures

Primary Outcomes (1)

• Improvement of DILI on the second week

  TBIL level decreases by 50% as compared to the baseline level.

  2 weeks

Secondary Outcomes (9)

• Improvement of DILI on the fourth week

  4 weeks

• Progressive liver injury on the second week

  2 weeks

• Progressive liver injury on the fourth week

  4 weeks

• Improvement of liver enzymes on the second week

  2 weeks

• Improvement of liver enzymes on the fourth week

  4 weeks

Other Outcomes (2)

• Population who will be more suitable for glucocorticoids treatment

  3 months

• Changes of inflammatory factors

  4 weeks

Study Arms (2)

Glucocorticoids group

EXPERIMENTAL

Glucocorticoids step-down therapy combined with conventional treatment.

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

Conventional treatment

ACTIVE COMPARATOR

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

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

Interventions

Methylprednisolone DRUG

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.

Also known as: Medrol

Glucocorticoids group

Magnesium isoglycyrrhizinate DRUG

It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 0.15g to 0.2g

Conventional treatment; Glucocorticoids group

Glutathione DRUG

It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 1.2g to 1.8g

Conventional treatment; Glucocorticoids group

Silymarin DRUG

It is suitable for patients with hepatocellular or mixed DILI. The dosage is 140 mg, taken 2 to 3 times per day.

Also known as: Legalon

Conventional treatment; Glucocorticoids group

Polyene Phosphatidylcholine DRUG

It is suitable for patients with hepatocellular or mixed DILI. The dosage is 228mg-456mg, taken 3 times per day.

Also known as: Essentiale

Conventional treatment; Glucocorticoids group

Ursodeoxycholic acid capsules DRUG

It is suitable for patients with cholestatic or mixed DILI. A daily dose of 10mg-15mg/kg/day.

Also known as: Ursofalk

Conventional treatment; Glucocorticoids group

Plaslna exchange PROCEDURE

It is suitable for patients whose condition continues to worsen or even develop to liver failure.

Also known as: Artificial liver support

Conventional treatment; Glucocorticoids group

Liver transplantation PROCEDURE

It is suitable for patients whose condition continues to worsen or even develop to liver failure.

Conventional treatment; Glucocorticoids group

Ademetionine 1,4-Butanedisulfonate DRUG

It is suitable for patients with cholestatic or mixed DILI. A daily dose of 0.5g to 1g.

Also known as: Transmeti

Conventional treatment; Glucocorticoids group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A definite diagnosis of acute DILI;
• ×ULN ≤ TBIL level at baseline ≤ 20×ULN;
• Age 18-80 years old;
• Sign the informed consent form.

You may not qualify if:

• 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;

Sponsors & Collaborators

• General Hospital of Shenyang Military Region: lead

Study Sites (1)

Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area)

Shenyang, Liaoning, 110840, China

RECRUITING

Related Publications (4)

• Hou FQ, Zeng Z, Wang GQ. Hospital admissions for drug-induced liver injury: clinical features, therapy, and outcomes. Cell Biochem Biophys. 2012 Nov;64(2):77-83. doi: 10.1007/s12013-012-9373-y.

  PMID: 22806342 RESULT

• Hu PF, Wang PQ, Chen H, Hu XF, Xie QP, Shi J, Lin L, Xie WF. Beneficial effect of corticosteroids for patients with severe drug-induced liver injury. J Dig Dis. 2016 Sep;17(9):618-627. doi: 10.1111/1751-2980.12383.

  PMID: 27426618 RESULT

• Chai L, Wang R, Teschke R, Jin S, Deng J, Qi X. Successful corticosteroid therapy for severe liver injury secondary to herbal traditional Chinese medicine, Mega Defends X, assessed for causality by the updated RUCAM: A case report. Medicine (Baltimore). 2024 Aug 23;103(34):e39439. doi: 10.1097/MD.0000000000039439.

  PMID: 39183394 RESULT

• Mao Y, Ma S, Liu C, Liu X, Su M, Li D, Li Y, Chen G, Chen J, Chen J, Zhao J, Guo X, Tang J, Zhuge Y, Xie Q, Xie W, Lai R, Cai D, Cai Q, Zhi Y, Li X; Technology Committee on DILI Prevention, Management, Chinese Medical Biotechnology Association; Study Group on Drug-Induced Liver Disease, Chinese Society of Hepatology, Chinese Medical Association. Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update. Hepatol Int. 2024 Apr;18(2):384-419. doi: 10.1007/s12072-023-10633-7. Epub 2024 Feb 24.

  PMID: 38402364 RESULT

MeSH Terms

Conditions

Chemical and Drug Induced Liver Injury; Liver Failure; Hyperbilirubinemia

Interventions

Methylprednisolone; 18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate; Glutathione; Silymarin; polyene phosphatidylcholine; essential 303 forte; Ursodeoxycholic Acid; Liver Transplantation

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning; Hepatic Insufficiency; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Cholanes; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation

Study Officials

• Xingshun Qi

  Department of Gastroenterology, General Hospital of Northern Theater Command

  PRINCIPAL INVESTIGATOR

• Weifen Xie

  Shanghai changzheng hospital, Naval Medical University

  PRINCIPAL INVESTIGATOR

• Xin Zeng

  Shanghai East Hospital,Tongji University School of Medicine

  PRINCIPAL INVESTIGATOR

• Lu Zhou

  General Hospital, Tianjin Medical University

  PRINCIPAL INVESTIGATOR

• Fengmei Wang

  Tianjin First Central Hospital

  PRINCIPAL INVESTIGATOR

• Qing Ye

  Tianjin Third Central Hospital

  PRINCIPAL INVESTIGATOR

• Yanjing Gao

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingshun Qi

CONTACT

18909881019; xingshunqi@126.com

Qianqian Li

CONTACT

13940307473; 1208594776@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Gastroenterology

Study Record Dates

• First Submitted: April 3, 2025
• First Posted: April 10, 2025
• Study Start: June 24, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)