Clinical trial NCT06922669: Glucocorticoids for Acute Drug Induced Liver Injury With Hyperbilirubinemia
Official title: Efficacy and Safety of Glucocorticoids for Acute Drug Induced Liver Injury With Hyperbilirubinemia: A Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Drug Induced Liver Injury
Keywords: Drug induced liver injury
liver failure
glucocorticoids
clinical trial
Hyperbilirubinemia
Lead sponsor: General Hospital of Shenyang Military Region
Sponsor class: OTHER
First posted: 2025-04-10
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Improvement of DILI on the second week
timeFrame: 2 weeks
Secondary outcomes:
measure: Improvement of DILI on the fourth week
timeFrame: 4 weeks
measure: Progressive liver injury on the second week
timeFrame: 2 weeks
measure: Progressive liver injury on the fourth week
timeFrame: 4 weeks
measure: Improvement of liver enzymes on the second week
timeFrame: 2 weeks
measure: Improvement of liver enzymes on the fourth week
timeFrame: 4 weeks
measure: Liver failure
timeFrame: 3 months
measure: Liver transplantation
timeFrame: 3 months
measure: Survival
timeFrame: 3 months
measure: Adverse events
timeFrame: 3 months
Other outcomes:
measure: Population who will be more suitable for glucocorticoids treatment
timeFrame: 3 months
measure: Changes of inflammatory factors
timeFrame: 4 weeks
Locations:
city: Shenyang
country: China
facility: Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area)
state: Liaoning
Study officials:
affiliation: Department of Gastroenterology, General Hospital of Northern Theater Command
name: Xingshun Qi
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Changzheng Hospital, Naval Medical University
name: Weifen Xie
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai East Hospital,Tongji University School of Medicine
name: Xin Zeng
role: PRINCIPAL_INVESTIGATOR
affiliation: General Hospital, Tianjin Medical University
name: Lu Zhou
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin First Central Hospital
name: Fengmei Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Third Central Hospital
name: Qing Ye
role: PRINCIPAL_INVESTIGATOR
affiliation: Qilu Hospital of Shandong University
name: Yanjing Gao
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.