Alcoholic HepatitisPhase 3GraCiAHNCT02442180
Efficacy and Safety of G-CSF in Patients With Severe Alcoholic Hepatitis With Null or Partial Response to Steroid
A Phase 3 study testing G-CSF (Filgrastim injection) and steroid in people with Alcoholic Hepatitis, run by Chuncheon Sacred Heart Hospital at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 79 years
- Conditions the study is for
- Alcoholic Hepatitis
- What is being tested?
- G-CSF (Filgrastim injection) and steroid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jul 2015to Jul 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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-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.
Read the 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.
- Conditions
- Alcoholic Hepatitis
- Being tested
- G-CSF (Filgrastim injection), steroid, placebo
- Medical subject headings
- Hepatitis, Alcoholic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
G-CSF (Filgrastim injection)Drug
Also called Filgrastim (brand name), Recombinant Filgrastim
G-CSF (Filgrastim injection) 5ug/kg subcutaneous injection daily for 5 days and every 3 days (total 12 doses)
steroidDrug
Also called prednisolone or methylprednisolone
oral prednisolone 40mg qd or iv methylprednisolone 32 mg if oral medication is not tolerable
placeboDrug
Also called normal saline
equivalent to G-CSF doses
| Study group | Role | What they receive |
|---|---|---|
| G-CSF + steroid in partial responder | Experimental | Patients who are randomized to prednisolone plus G-CSF treatment group in patients with partial responder to prednisolone therapy. Receives: Drug: G-CSF (Filgrastim injection); Drug: steroid |
| Placebo + steroid in partial responder | Placebo comparator | Patients who are randomized to prednisolone plus placebo treatment group in patients with partial responder to prednisolone therapy. Receives: Drug: steroid; Drug: placebo |
| G-CSF in null responder to steroid | Experimental | Patients who are randomized to G-CSF treatment group in patients with null responder to prednisolone therapy. Receives: Drug: G-CSF (Filgrastim injection) |
| Placebo in null responder to steroid | Placebo comparator | Patients who are randomized to placebo treatment group in patients with null responder to prednisolone therapy. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-month survival rate of null responder to steroid treatment and 6-month survival rate of partial responder to steroid treatment
Survival status can be determined by the occurrence of mortality regardless of any cause of death.
Measured: 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
Secondary outcomes (5)
Hepatic function improvement as assessed by the Child-Pugh score
Hepatic function is defined as the Child-Pugh score.
Measured: 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
Hepatic function is defined as the MELD score.
Measured: 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
Hepatic function is defined as the CLIF-SOFA score.
Measured: 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
Hepatic function is defined as the CD34+ cell count percentage in circulating blood.
Measured: day0,7,35
Hepatic function improvement as assessed by the Alcoholic Hepatitis Histology score
Hepatic function is defined as histological scoring system of alcoholic hepatitis (AHHS).
Measured: day0,35
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2015 (estimated)
- Study startJul 2015
- Primary completionJul 2022
- Study completionJul 2022
Why it stopped: failure to recruit eligible patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alcoholic HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chuncheon Sacred Heart Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dong Joon Kim, Chuncheon Sacred Heart Hospital
- Investigators
- Dong Joon Kim, M.D., Ph.D., Principal investigator, Hallym Universitiy College of Medicine, Chuncheon Sacred Heart hospital, Chuncheon, South Korea
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02442180
- Sponsor's protocol ID
- 2014-6
- Acronym
- GraCiAH
- Status last verified
- Aug 2022
- First submitted
- 2 May 2015
- Last updated
- 8 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Cho Y, Park YS, Kim HY, Kim W, Lee HJ, Kim DJ. Efficacy of granulocyte colony stimulating factor in patients with severe alcoholic hepatitis with partial or null response to steroid (GRACIAH trial): study protocol for a randomized controlled trial. Trials. 2018 Dec 22;19(1):696. doi: 10.1186/s13063-018-3092-7.
PubMed 30577864
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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-blind, Placebo-controlled, Nationwide Multi-center Study
- ClinicalTrials.gov ID
- NCT02442180
- Acronym / sponsor ID
- GraCiAH / 2014-6
- Conditions
- Alcoholic Hepatitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: failure to recruit eligible patients
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Chuncheon Sacred Heart HospitalUniversity, hospital or other
- Study start
- Jul 2015 (actual)
- Primary completion
- Jul 2022 (actual)
- Study completion
- Jul 2022 (actual)
- First posted
- 13 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| G-CSF + steroid in partial responder | Experimental | Drug: G-CSF (Filgrastim injection), Drug: steroidPatients who are randomized to prednisolone plus G-CSF treatment group in patients with partial responder to prednisolone therapy. |
| Placebo + steroid in partial responder | Placebo comparator | Drug: steroid, Drug: placeboPatients who are randomized to prednisolone plus placebo treatment group in patients with partial responder to prednisolone therapy. |
| G-CSF in null responder to steroid | Experimental | Drug: G-CSF (Filgrastim injection)Patients who are randomized to G-CSF treatment group in patients with null responder to prednisolone therapy. |
| Placebo in null responder to steroid | Placebo comparator | Drug: placeboPatients who are randomized to placebo treatment group in patients with null responder to prednisolone therapy. |
Who may qualify
- Ages
- 21 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| G-CSF (Filgrastim injection)Also: Filgrastim (brand name), Recombinant FilgrastimG-CSF (Filgrastim injection) 5ug/kg subcutaneous injection daily for 5 days and every 3 days (total 12 doses) | Drug | G-CSF + steroid in partial responder, G-CSF in null responder to steroid |
| steroidAlso: prednisolone or methylprednisoloneoral prednisolone 40mg qd or iv methylprednisolone 32 mg if oral medication is not tolerable | Drug | G-CSF + steroid in partial responder, Placebo + steroid in partial responder |
| placeboAlso: normal salineequivalent to G-CSF doses | Drug | Placebo + steroid in partial responder, Placebo in null responder to steroid |
Primary outcome
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
Survival status can be determined by the occurrence of mortality regardless of any cause of death.
5 secondary outcomes
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
Results and safety
The study was stopped early (reason given: failure to recruit eligible patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2022.
- Derived from this study: PubMed 30577864Cho Y, Park YS, Kim HY, Kim W, Lee HJ, Kim DJ. Efficacy of granulocyte colony stimulating factor in patients with severe alcoholic hepatitis with partial or null response to steroid (GRACIAH trial): study protocol for a randomized controlled trial. Trials. 2018 Dec 22;19(1):696. doi: 10.1186/s13063-018-3092-7.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dong Joon Kim, M.D., Ph.D. principal investigator
Hallym Universitiy College of Medicine, Chuncheon Sacred Heart hospital, Chuncheon, South Korea
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing G-CSF (Filgrastim injection) and steroid in people with Alcoholic Hepatitis, run by Chuncheon Sacred Heart Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: failure to recruit eligible patients). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02442180, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2022.