Clinical trial NCT02651350: Efficacy and Safety of Glucocorticosteroid Treatment in the Patients With Chronic Recurrent DILI
Official title: A Randomized Controlled Clinical Trial on the Efficacy and Safety of Glucocorticosteroid in the Patients With Chronic Recurrent Drug-induced Liver Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Drug-induced Liver Injury,Chronic
Keywords: Drug-induced Liver Injury
Recurrence
Methylprednisolone
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
First posted: 2016-01-11
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to observe the efficacy and safety of glucocorticosteroid treatment in the patients with chronic recurrent drug-induced liver injury (DILI).

Detailed description: Drug-induced liver injury (DILI) refers to liver diseases caused by drugs and toxic substances. DILI is a clinical event that can be associated with severe outcomes such as acute liver failure. Up to now, approximately 1000 drugs, herbal products, vitamins and illicit compounds are associated with liver injury. Recently, the incidence of DILI is rising. In our hospital, hospitalized patients with DILI was increased from 1.39% in 2002 to 2.31% in 2006, and further up to 3.17% in 2011, which indicated 2.3-folds increase over last ten years.15% to 20% patients with acute DILI are prone to chronic liver disease. For patients with chronic recurrent DILI, routine liver protective treatment was difficult to rescue abnormal liver functions. Moreover, increasing health care costs seriously affect the patient's quality of life. Glucocorticosteroids can inhibit the non-specific inflammation and permeability of the capillary bile duct, limit the activation of T lymphocytes, and selectively inhibit B lymphocytes to produce antibodies, thus preventing or delaying the immune-induced liver injury. Glucocorticoid treatment of severe DILI has accepted some recognition, but the effect of repeated episodes of chronic DILI, due to a lack of randomized controlled studies, is still unclear. Therefore, we shall design two groups on the basis of the ratio of 1:1, namely, glucocorticoid treatment group and standard treatment alone group. Participants in glucocorticoid treatment group will receive methylprednisolone,48mg/d for the 1st week, 32mg/d for the 2nd week, 24mg/d for the next two weeks, followed by 16mg/d for 32 weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal. Participants in glucocorticoid treatment group also receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) in the first 12 weeks. Participants in standard treatment group will only receive treatment by routine liver protection drugs including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA) in the first 12 weeks.The efficacy and safety of glucocorticoid treatment in the patients with chronic recurrent DILI will be observed during the treatment and follow-up period.

Eligibility criteria: Inclusion Criteria:

1. Meet with ACG clinic guidelines for diagnostic criteria of chronic DILI;
2. Meet any of the following conditions:

   * serum AST or ALT ≥ 10 fold ULN;
   * serum AST or ALT ≥ 5 fold ULN and TBIL ≥ 2 fold ULN;
   * liver histology indicates bridging necrosis or multiacinar necrosis or moderate or more inflammation or inflammation G3 or more;
3. Women of childbearing age had a negative urine pregnancy test, and the subjects are willing to have no family planning during the study and to take effective measures;
4. Voluntary participation, understanding and signing of informed consent, comply with the requirements of the research;

Exclusion Criteria:

1. Patients with serious pre-existent comorbid conditions (vertebral compression fractures,psychosis,active peptic ulcer, brittle diabetes,uncontrolled hypertension;
2. Patients with intolerances to prednisone;
3. Patients with severe infection receiving antibiotics, anti-fungal,anti-viral therapy;
4. Viral hepatitis,alcoholic or non-alcoholic liver disease,Wilson's disease or other inherited metabolic liver diseases.
5. Pregnancy or desire of pregnancy;
6. Breast-feeding;
7. Liver cancer or other malignant tumor;

Primary outcomes:
measure: The relapse or recurrent rate of illness, namely, appearance of obviously abnormal liver function again during treatment and follow-up period
timeFrame: At week 24
measure: The relapse or recurrent rate of illness, namely, appearance of obviously abnormal liver function again during treatment and follow-up period
timeFrame: At week 72
Secondary outcomes:
measure: Days of normalization of liver functions including serum levels of ALT, AST, TBIL,GGT and ALP.
timeFrame: From week 1 to week 12
measure: The liver histological changes between two liver biopsies
timeFrame: At week 0 and at week 48 week
measure: The number of participants with methylprednisolone treatment-related adverse events, such as severe osteopenia, uncontrolled hypertension
timeFrame: At week 24 and at week 72
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing 302 hospital,China
state: Beijing
Study officials:
affiliation: Beijing 302 Hospital,China.
name: Zhengsheng Zou, Dr.
role: PRINCIPAL_INVESTIGATOR
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