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Trial record 78 of 581 for:    reduced glutathione

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

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ClinicalTrials.gov Identifier: NCT02651350
Recruitment Status : Active, not recruiting
First Posted : January 11, 2016
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
Beijing 302 Hospital

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).

Condition or disease Intervention/treatment Phase
Drug-induced Liver Injury,Chronic Drug: Methylprednisolone Drug: Standard Treatment Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : December 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: 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.
Drug: 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.
Other Name: MEDROL,NDC0009-0056-02

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.
Other Name: Routine liver protection drugs

Active Comparator: 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.
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.
Other Name: Routine liver protection drugs




Primary Outcome Measures :
  1. The relapse or recurrent rate of illness, namely, appearance of obviously abnormal liver function again during treatment and follow-up period [ Time Frame: At week 24 ]
  2. The relapse or recurrent rate of illness, namely, appearance of obviously abnormal liver function again during treatment and follow-up period [ Time Frame: At week 72 ]

Secondary Outcome Measures :
  1. Days of normalization of liver functions including serum levels of ALT, AST, TBIL,GGT and ALP. [ Time Frame: From week 1 to week 12 ]
  2. The liver histological changes between two liver biopsies [ Time Frame: At week 0 and at week 48 week ]
  3. The number of participants with methylprednisolone treatment-related adverse events, such as severe osteopenia, uncontrolled hypertension [ Time Frame: At week 24 and at week 72 ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02651350


Locations
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China, Beijing
Beijing 302 hospital,China
Beijing, Beijing, China, 100039
Sponsors and Collaborators
Beijing 302 Hospital
Investigators
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Principal Investigator: Zhengsheng Zou, Dr. Beijing 302 Hospital,China.

Publications:

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Responsible Party: Beijing 302 Hospital
ClinicalTrials.gov Identifier: NCT02651350     History of Changes
Other Study ID Numbers: BJ302-FGRXGB-001
First Posted: January 11, 2016    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Beijing 302 Hospital:
Drug-induced Liver Injury
Recurrence
Methylprednisolone

Additional relevant MeSH terms:
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Chemical and Drug Induced Liver Injury
Chemical and Drug Induced Liver Injury, Chronic
Liver Diseases
Digestive System Diseases
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Poisoning
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Glycyrrhizic Acid
Prednisolone hemisuccinate
Prednisolone phosphate
Ursodeoxycholic Acid
Alprostadil
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents