- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02442180
Efficacy and Safety of G-CSF in Patients With Severe Alcoholic Hepatitis With Null or Partial Response to Steroid (GraCiAH)
August 4, 2022 updated by: Dong Joon Kim, Chuncheon Sacred Heart Hospital
Efficacy and Safety of Granulocyte-colony Stimulating Factor in Patients With Severe Alcoholic Hepatitis With Null or Partial Response to Steroid: A Randomized, Double-blind, Placebo-controlled, Nationwide Multi-center Study
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
64
Phase
- Phase 3
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
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Chuncheon, Korea, Republic of
- Chuncheon Sacred Heart Hospital
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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
19 years to 77 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria: Patients with
- Clinical significant alcohol intake history (men over 50g within 3 months, women over 40g within 3 months)
- modified DF score greater than or equal to 32
- Transjugular liver biopsy shows typical feature of alcoholic hepatitis or meet the clinical diagnosis (total serum bilirubin level over 5 mg/dL, aspartate aminotransferase/alanine aminotransferase ratio >2, aspartate aminotransferase < 300 IU/L)
- Included patients should meet the all above criteria and Lille score > 0.16 at the day 7 of prednisolone 40mg (or 32 mg of methylprednisolone) daily treatment.
Exclusion Criteria: Patients with
- hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), or anti-human immunodeficiency virus (HIV) (+)
- Malignancy including hepatocellular carcinoma
- Portal vein thrombosis, hemochromatosis, autoimmune hepatitis, Wilson's disease, alpha-1-antitrypsin deficiency
- Pregnancy, breast feeding, or who refuses contraception, or who cannot do contraception
- History of adverse event including allergic response, hypersensitivity to G-CSF
- Hypovolemic shock due to gastrointestinal hemorrhage or who need packed red blood cell (RBC) transfusion more than 3 units or increased modified discriminant factor (DF) score greater or equal to 32 from below 32 due to gastrointestinal hemorrhage
- Sepsis or uncontrolled acute infection
- Hepatic encephalopathy grade 3-4
- History of steroid or pentoxifylline treatment within 3 months
- Myeloblast on peripheral blood smear test
- Critical comorbidities (type I hepatorenal syndrome, serum creatinine >2.5mg/dL, heart failure, pulmonary disease, psychiatric disease, acute pancreatitis etc.)
- Who refuses to participate in clinical trial
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: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: G-CSF + steroid in partial responder
Patients who are randomized to prednisolone plus G-CSF treatment group in patients with partial responder to prednisolone therapy.
|
G-CSF (Filgrastim injection) 5ug/kg subcutaneous injection daily for 5 days and every 3 days (total 12 doses)
Other Names:
oral prednisolone 40mg qd or iv methylprednisolone 32 mg if oral medication is not tolerable
Other Names:
|
Placebo Comparator: Placebo + steroid in partial responder
Patients who are randomized to prednisolone plus placebo treatment group in patients with partial responder to prednisolone therapy.
|
oral prednisolone 40mg qd or iv methylprednisolone 32 mg if oral medication is not tolerable
Other Names:
equivalent to G-CSF doses
Other Names:
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Experimental: G-CSF in null responder to steroid
Patients who are randomized to G-CSF treatment group in patients with null responder to prednisolone therapy.
|
G-CSF (Filgrastim injection) 5ug/kg subcutaneous injection daily for 5 days and every 3 days (total 12 doses)
Other Names:
|
Placebo Comparator: Placebo in null responder to steroid
Patients who are randomized to placebo treatment group in patients with null responder to prednisolone therapy.
|
equivalent to G-CSF doses
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
2-month survival rate of null responder to steroid treatment and 6-month 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
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Survival status can be determined by the occurrence of mortality regardless of any cause of death.
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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
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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Hepatic function is defined as the Child-Pugh score.
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day 0,1,3,7,9,11,14,17,20,23,26,29,32,35,60,90,120,150,180
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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
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Hepatic function is defined as the MELD score.
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day 0,1,3,7,9,11,14,17,20,23,26,29,32,35,60,90,120,150,180
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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 is defined as the CLIF-SOFA score.
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day 0,1,3,7,9,11,14,17,20,23,26,29,32,35,60,90,120,150,180
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Hepatic function improvement as assessed by the Fraction of Cluster of differentiation (CD34)+ cell in peripheral blood
Time Frame: day0,7,35
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Hepatic function is defined as the CD34+ cell count percentage in circulating blood.
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day0,7,35
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Hepatic function improvement as assessed by the Alcoholic Hepatitis Histology score
Time Frame: day0,35
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Hepatic function is defined as histological scoring system of alcoholic hepatitis (AHHS).
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day0,35
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Dong Joon Kim, M.D., Ph.D., Hallym Universitiy College of Medicine, Chuncheon Sacred Heart hospital, Chuncheon, South Korea
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.
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)
July 1, 2015
Primary Completion (Actual)
July 1, 2022
Study Completion (Actual)
July 1, 2022
Study Registration Dates
First Submitted
May 2, 2015
First Submitted That Met QC Criteria
May 8, 2015
First Posted (Estimate)
May 13, 2015
Study Record Updates
Last Update Posted (Actual)
August 8, 2022
Last Update Submitted That Met QC Criteria
August 4, 2022
Last Verified
August 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Chemically-Induced Disorders
- Digestive System Diseases
- Alcohol-Related Disorders
- Substance-Related Disorders
- RNA Virus Infections
- Virus Diseases
- Infections
- Liver Diseases
- Hepatitis, Viral, Human
- Enterovirus Infections
- Picornaviridae Infections
- Liver Diseases, Alcoholic
- Alcohol-Induced Disorders
- Hepatitis
- Hepatitis A
- Hepatitis, Alcoholic
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Adjuvants, Immunologic
- Prednisolone
- Methylprednisolone
- Lenograstim
Other Study ID Numbers
- 2014-6
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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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