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

Primary Purpose

Drug-induced Liver Injury,Chronic

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
36 Weeks Methylprednisolone
48 weeks Methylprednisolone
Sponsored by
Beijing 302 Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Drug-induced Liver Injury,Chronic focused on measuring Drug-induced Liver Injury, Recurrence, Methylprednisolone, Short-term

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Beijing 302 hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

36 Weeks Methylprednisolone

48 Weeks Methylprednisolone

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
To analyze the clinical efficacy of glucocorticosteroid treatment

Secondary Outcome Measures

The liver histological changes between two liver biopsies (baseline and treatment end)
To analyze the clinical efficacy of glucocorticosteroid treatment
Days of normalization or falling by half compared to admission of liver functions including serum levels of ALT, AST, TBIL,GGT and ALP.
To analyze the clinical efficacy of glucocorticosteroid treatment

Full Information

First Posted
August 26, 2017
Last Updated
February 13, 2023
Sponsor
Beijing 302 Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03266146
Brief Title
36 Weeks Short-Term Optimization Treatment of Glucocorticosteroid in the Patients With Chronic Recurrent DILI
Official Title
The Efficacy and Safety of 36 Weeks Short-Term Optimization Treatment of Glucocorticosteroid in the Patients With Chronic Recurrent Drug-Induced Liver Injury
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
September 2, 2017 (Actual)
Primary Completion Date
January 31, 2023 (Actual)
Study Completion Date
January 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing 302 Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Drug-induced Liver Injury,Chronic
Keywords
Drug-induced Liver Injury, Recurrence, Methylprednisolone, Short-term

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
36 Weeks Methylprednisolone
Arm Type
Experimental
Arm Description
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.
Arm Title
48 Weeks Methylprednisolone
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
36 Weeks Methylprednisolone
Other Intervention Name(s)
MEDROL,NDC0009-0056-02
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
48 weeks Methylprednisolone
Other Intervention Name(s)
MEDROL,NDC0009-0056-02
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
To analyze the clinical efficacy of glucocorticosteroid treatment
Time Frame
From week 1 to week 60 or 72
Secondary Outcome Measure Information:
Title
The liver histological changes between two liver biopsies (baseline and treatment end)
Description
To analyze the clinical efficacy of glucocorticosteroid treatment
Time Frame
At week 0 and at week 36 week or 48 week
Title
Days of normalization or falling by half compared to admission of liver functions including serum levels of ALT, AST, TBIL,GGT and ALP.
Description
To analyze the clinical efficacy of glucocorticosteroid treatment
Time Frame
From week 1 to week 36 or 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Meet with ACG clinic guidelines for diagnostic criteria of chronic DILI; 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; 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; 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; Voluntary participation, understanding and signing of informed consent, comply with the requirements of the research. - Exclusion Criteria: Patients with serious pre-existent comorbid conditions (vertebral compression fractures,psychosis,active peptic ulcer, brittle diabetes,uncontrolled hypertension; Patients with intolerances to prednisone; Patients with severe infection receiving antibiotics, anti-fungal,anti-viral therapy; Viral hepatitis,alcoholic or non-alcoholic liver disease,Wilson's disease or other inherited metabolic liver diseases. Pregnancy or desire of pregnancy; Breast-feeding; Liver cancer or other malignant tumor.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhengsheng Zou, Dr.
Organizational Affiliation
Beijing 302 Hospital,China.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing 302 hospital
City
Beijing
ZIP/Postal Code
100039
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
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36 Weeks Short-Term Optimization Treatment of Glucocorticosteroid in the Patients With Chronic Recurrent DILI

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