Clinical Trial: Efficacy and Safety of G-CSF in Patients With Severe Alcoholic Hepatitis With Null or Partial Response to Steroid

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Efficacy and Safety of Granulocyte-colony Stimulating Factor in Patients With Severe Alcoholic Hepatitis With Null or Partial Response to Steroid: A Randomized, Double-bli

Brief Summary: Steroid is the treatment of choice in patients with severe alcoholic hepatitis. However, null- or partial responder of steroid treatment is recommended to consider liver transplantation. The yearly demand for liver transplants far exceeds the supply of available organs and alcoholic liver disease has been a controversial indication for transplantation. Granulocyte-Colony Stimulating Factor (G-CSF) has been reported to have effect of proliferation of hepatic progenitors in alcoholic steatohepatitis. The aim of this study is to investigate the efficacy of G-CSF in patients with severe alcoholic hepatitis with null or partial response to steroid.

Detailed Summary: Severe alcoholic hepatitis is defined as alcoholic hepatitis patients having discriminant function (DF) score over 32 or accompanying hepatic encephalopathy. These patients have shown poor prognosis of 28 day mortality as 30 to 50% without treatment. Steroid (prednisolone 40mg/day for 28 days) is the treatment of choice in patients with severe alcoholic hepatitis. Alcoholic hepatitis with modified DF score greater than or equal to 32 or model for end-stage liver disease (MELD) score over 21 or with hepatic encephalopathy are indications. However, null- or partial responder of steroid treatment is recommended to consider liver transplantation. The yearly demand for liver transplants far exceeds the supply of available organs and alcoholic liver disease has been a controversial indication for transplantation. Even in the responders of steroid treatment, the mortality is still 20% (from 40% without treatment to 20% with steroid treatment). There is a need for development of new treatment for this catastrophic disease. Granulocyte-Colony Stimulating Factor (G-CSF) has been reported to have effect of proliferation of hepatic progenitors in alcoholic steatohepatitis. The aim of this study is to investigate the efficacy of G-CSF in patients with severe alcoholic hepatitis with null or partial response to steroid.
Sponsor: Chuncheon Sacred Heart Hospital

Current Primary Outcome: 2 months survival rate of null responder to steroid treatment and 6 months survival rate of partial responder to steroid treatment [ Time Frame: After 2 months of G-CSF or placebo treatment in patients with null responder to steroid treatment and after 6 months of G-CSF+steroid or only steroid treatment in patients with partial responder to steroid treatment ]

Original Primary Outcome:

  • 2 months survival rate of null responder to steroid treatment [ Time Frame: After 2 months of G-CSF or placebo treatment in patients with null responder to steroid treatment ]
  • 6 months survival rate of partial responder to steroid treatment [ Time Frame: After 6 months of G-CSF+steroid or only steroid treatment in patients with partial responder to steroid treatment ]


Current Secondary Outcome:

  • Hepatic function improvement as assessed by the Child-Pugh score [ Time Frame: day 0,1,3,7,9,11,14,17,20,23,26,29,32,35,60,90,120,150,180 ]
  • Hepatic function improvement as assessed by the MELD score [ Time Frame: day 0,1,3,7,9,11,14,17,20,23,26,29,32,35,60,90,120,150,180 ]
  • Hepatic function improvement as assessed by the Chronic Liver Failure (CLIF)-Sequential Organ Failure Assessment (SOFA) score [ Time Frame: day 0,1,3,7,9,11,14,17,20,23,26,29,32,35,60,90,120,150,180 ]
  • Hepatic function improvement as assessed by the Fraction of Cluster of differentiation (CD34)+ cell in peripheral blood [ Time Frame: day0,7,35 ]
  • Hepatic function improvement as assessed by the Alcoholic Hepatitis Histology score [ Time Frame: day0,35 ]
    liver biopsy


Original Secondary Outcome:

  • Hepatic function improvement assessed by the Child-Pugh score [ Time Frame: day 0,1,3,7,9,11,14,17,20,23,26,29,32,35,60,90,120,150,180 ]
  • Hepatic function improvement assessed by the MELD score [ Time Frame: day 0,1,3,7,9,11,14,17,20,23,26,29,32,35,60,90,120,150,180 ]
  • Hepatic function improvement assessed by the CLIP-SOFA score [ Time Frame: day 0,1,3,7,9,11,14,17,20,23,26,29,32,35,60,90,120,150,180 ]
  • Hepatic function improvement assessed by the Fraction of CD34+ cell in peripheral blood [ Time Frame: day0,7,35 ]
  • Hepatic function improvement assessed by the Alcoholic Hepatitis Histology score [ Time Frame: day0,35 ]
    liver biopsy


Information By: Chuncheon Sacred Heart Hospital

Dates:
Date Received: May 2, 2015
Date Started: July 2015
Date Completion: December 2020
Last Updated: May 4, 2016
Last Verified: December 2015