36 Weeks Short-Term Optimization Treatment of Glucocorticosteroid in the Patients With Chronic Recurrent DILI
Condition: Drug-induced Liver Injury,Chronic
MeSH terms: Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): 36 Weeks Methylprednisolone; 48 weeks Methylprednisolone
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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 intervention name(s): MEDROL,NDC0009-0056-02; MEDROL,NDC0009-0056-02
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug-induced Liver Injury; Recurrence; Methylprednisolone; Short-term