Efficacy and Safety of Glucocorticosteroid Treatment in the Patients With Chronic Recurrent DILI

NCT ID: NCT02651350

Last Updated: 2020-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2019-07-31

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.

Conditions

Drug-induced Liver Injury,Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Methylprednisolone

Participants will receive methylprednisolone from week 0 through week 48 study visit in combination with standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) in the first 12 weeks. Participants will then be followed until week 72 study visit.

Group Type: EXPERIMENTAL

Methylprednisolone

Intervention Type: DRUG

Participants 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 will also receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA) in the first 12 weeks.The total treatment duration will be 48 weeks. Follow-up duration is 24 weeks.

Standard Treatment

Intervention Type: DRUG

Participants will only receive standard treatment,namely,routine liver protection drugs including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) from week 0 through week 12 study visit. Participants will then be followed until week 72.

Standard Treatment

Participants will only receive standard treatment (namely,routine liver protection drugs) including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) from week 0 through week 12 study visit. Participants will then be followed until week 72 study visit.

Group Type: ACTIVE_COMPARATOR

Standard Treatment

Intervention Type: DRUG

Participants will only receive standard treatment,namely,routine liver protection drugs including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) from week 0 through week 12 study visit. Participants will then be followed until week 72.

Interventions

Methylprednisolone

Participants 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 will also receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA) in the first 12 weeks.The total treatment duration will be 48 weeks. Follow-up duration is 24 weeks.

Intervention Type: DRUG

Standard Treatment

Participants will only receive standard treatment,namely,routine liver protection drugs including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) from week 0 through week 12 study visit. Participants will then be followed until week 72.

Intervention Type: DRUG

Other Intervention Names

MEDROL,NDC0009-0056-02; Routine liver protection drugs

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing 302 Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhengsheng Zou, Dr.

Role: PRINCIPAL_INVESTIGATOR

Beijing 302 Hospital,China.

Locations

Beijing 302 hospital,China

Beijing, Beijing Municipality, China

Countries

China

References

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Other Identifiers

BJ302-FGRXGB-001

Identifier Type: -

Identifier Source: org_study_id