Granulocyte Colony Stimulating Factor in Alcoholic Hepatitis
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Survival at 3 months
研究概览
简要总结
Alcoholic hepatitis is related to very high mortality rate. About 40% of the patients are died within first 6 months after the detection of the clinical syndrome. Therefore, it is very essential for proper diagnosis and early treatment. In response to acute or chronic liver damage, bone marrow derived stem cells can spontaneously populate liver and differentiate into hepatic cells. Animal and human studies suggested that injured hepatocyte may be replaced by pluripotent bone marrow cells. However, this hepatocyte repopulation is highly dependent on varieties of liver injury and therapeutic conditions. The studies has suggested Granulocyte-colony stimulating factors (G-CSF) can regenerate hepatocyte by fusing with hematopoietic cells, thereby enhancing the liver histology and survival rate.
G-CSF is a cytokine capable to regulate a number of functions in neutrophils. In three recent studies mobilization of bone marrow stem cells induced by G-CSF was observed in patients with alcoholic hepatitis. In two of this studies there was a survival benefit with the use of G-CSF.
Therefore we plan to study the safety and efficacy of G-CSF in the patients with alcoholic hepatitis.
详细描述
Detailed Description:
Patients with severe alcoholic hepatitis, admitted to Department of Hepatology PGIMER, Chandigarh will be included in the study.
METHODS
This will be an open label trial. A randomization code is generated by random number table. The patients will be randomized to receive standard medical therapy (SMT) only as control and therapy of G-CSF as case. There will be one control and one case as below:
- SMT (control) 2) G-CSF (case): G-CSF 5 mcg/kg every 12 hourly for consecutive 5 days This will be a single time therapy. Patients will be admitted in the department of hepatology and will be assessed everyday clinically as well as by laboratory tests during therapy to assess safety and effects of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Alcoholic hepatitis patients:
- •More than 10 years of heavy alcohol consumption (mean intake ≈ 100 g/day).
- •Elevated aspartate aminotransferase level (but <500 IU per millilitre) and Ratio ofAST/ALT≥2 times
- •Elevated serum total bilirubin level ≥ 5 mgdL (86 μmol/L)
- •Elevated INR(≥1.5) and
- •Neutrophilia. Patient with Maddrey's DF of ≥ 32 will be included in the study, with or without biopsy.
排除标准
- •Age < 18 and > 75 years
- •Hepatocellular carcinoma or portal vein thrombosis
- •Refusal to participate in the study
- •Serum creatinine>1.0 mg%
- •Hepatic encephalopathy- grade 3 or 4
- •Upper gastrointestinal bleed in last ten days
- •Uncontrolled bacterial infection
- •Human immunodeficiency virus, Hepatitis B virus, Hepatitis C virus seropositivity, Autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency
- •Glucocorticoid treatment
- •Significant co-morbidity
- •Previous known hypersensitivity to G-CSF
研究组 & 干预措施
Standard Medical Therapy
Drug: standard medical therapy Standard medical therapy involves primary treatment and normal hospital nutrition (1800 to 2000 kcal per day). Diuretics, sodium restriction and albumin for treatment of ascites or fresh frozen plasma for coagulopathy or antibiotics for any focus of infection as spontaneous bacterial peritonitis (SBP), pneumonia, cellulitis, and urinary tract infection as indicated.
干预措施: GCSF (Drug)
G-CSF + Standard Medical Therapy
Drug: standard medical therapy Standard medical therapy involves primary treatment and normal hospital nutrition (1800 to 2000 kcal per day). Diuretics, sodium restriction and albumin for treatment of ascites or fresh frozen plasma for coagulopathy or antibiotics for any focus of infection as spontaneous bacterial peritonitis (SBP), pneumonia, cellulitis, and urinary tract infection as indicated.
Drug: G-CSF G-CSF- 5 μg/Kg s.c every 12 hours for 5 consecutive days
干预措施: GCSF (Drug)
结局指标
主要结局
Survival at 3 months
时间窗: 90 DAYS
次要结局
- Mobilisation of CD34 positive cells in peripheral blood.(6 DAYS)
- Improvement in MELD score(90 DAYS)
- Improvement in Maddrey's Discriminant Function.(90 Days)
- Improvement in Child Turcotte Pugh score.(90 Days)
- Number of participants with treatment-related adverse events in the different groups.(90 Days)
研究者
Dr.Virendra Singh
Professor of Hepatology
Post Graduate Institute of Medical Education and Research, Chandigarh