36 Weeks Short-Term Optimization Treatment of Glucocorticosteroid in the Patients With Chronic Recurrent DILI

February 13, 2023 updated by: Beijing 302 Hospital

The Efficacy and Safety of 36 Weeks Short-Term Optimization Treatment of Glucocorticosteroid in the Patients With Chronic Recurrent Drug-Induced Liver Injury

This study is to observe the efficacy and safety of 36 weeks short-term optimization treatment of glucocorticosteroid in the patients with chronic recurrent drug-induced liver injury (DILI).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 1100 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. About 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. In our pre-clinical trials (NCT02651350), we found that the rate of recurrence of the glucocorticoid treatment group was significant lower (<10%) than the control group (about 50%) (P <0.001) and there was significant difference of liver histological change during baseline and treatment end between the glucocorticoid treatment group and the control group. Meanwhile, we did not find obvious glucocorticoid's side effect in the glucocorticoid treatment group. At the same time, we found that there was good effect in 36 weeks glucocorticoid treatment in several patients. Therefore, we shall design two groups on the basis of the ratio of 1:1, namely, 36 weeks of glucocorticoid treatment group and 48 weeks of glucocorticoid treatment group in order to evaluate the efficacy and safety of 36 weeks short-term optimization treatment of glucocorticosteroid in the patients with chronic recurrent DILI.

Participants in 36 weeks of 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 20 weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal. Participants in 36 weeks of glucocorticoid treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA).Participants will then be followed for 24 weeks. Participants in 48 weeks of 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 48 weeks of treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA).Participants will then be followed for 24 weeks.

The efficacy and safety of 36 weeks short-term optimization treatment of glucocorticosteroid in the patients with chronic recurrent DILI will be observed and compared with 48 weeks glucocorticosteroid treatment during the treatment and follow-up period.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100039
        • Beijing 302 Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Meet with ACG clinic guidelines for diagnostic criteria of chronic DILI;

  2. The time of recurrence is 1 or more than 1;

    The definition of recurrence, meet any of the following conditions:

    • the level of serum AST or ALT is elevated more than 5 fold ULN;
    • the level of serum AST or ALT is two times higher than before;

  3. 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;
  4. 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;

  5. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 36 Weeks Methylprednisolone
Participants in 36 weeks of 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 20 weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal. Participants in 36 weeks of glucocorticoid treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA). Participants will then be followed for 24 weeks.
Drug: 36 Weeks Methylprednisolone
Participants in 36 weeks of 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 20 weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal. Participants in 36 weeks of glucocorticoid treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA).The total treatment duration will be 36 weeks. Follow-up duration is 24 weeks.
Other Names:
  • MEDROL,NDC0009-0056-02
Experimental: 48 Weeks Methylprednisolone
Participants in 48 weeks of 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 48 weeks of treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA). Participants will then be followed for 24 weeks.
Drug: 48 weeks Methylprednisolone
Participants in 48 weeks of 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 36 weeks of glucocorticoid treatment group also will receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA).The total treatment duration will be 48 weeks. Follow-up duration is 24 weeks.
Other Names:
  • MEDROL,NDC0009-0056-02

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence rate of illness, namely, appearance of obviously abnormal liver function again during treatment and follow-up period. The definition of recurrence: The level of AST or ALT is elevated more than 5 fold ULN or is two times higher than before.
Time Frame: From week 1 to week 60 or 72
To analyze the clinical efficacy of glucocorticosteroid treatment
From week 1 to week 60 or 72

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The liver histological changes between two liver biopsies (baseline and treatment end)
Time Frame: At week 0 and at week 36 week or 48 week
To analyze the clinical efficacy of glucocorticosteroid treatment
At week 0 and at week 36 week or 48 week
Days of normalization or falling by half compared to admission of liver functions including serum levels of ALT, AST, TBIL,GGT and ALP.
Time Frame: From week 1 to week 36 or 48
To analyze the clinical efficacy of glucocorticosteroid treatment
From week 1 to week 36 or 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing 302 Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 2, 2017

Primary Completion (Actual)

January 31, 2023

Study Completion (Actual)

January 31, 2023

Study Registration Dates

First Submitted

August 26, 2017

First Submitted That Met QC Criteria

August 26, 2017

First Posted (Actual)

August 29, 2017

Study Record Updates

Last Update Posted (Actual)

February 15, 2023

Last Update Submitted That Met QC Criteria

February 13, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BJ302-FGRXGB-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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