National Collaborative Centre for Hepatic Regenerative Medicine(NC-CHRM): To Study the Efficacy of Single vs Repeated Cycle of GCSF+ Darbepoetin in Long Term Transplant Free Management of Patient With Early Decompensated Cirrhosis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Transplant-free survival of GCSF + darbepoetin in patients with early decompensated cirrhosis in both groups.
研究概览
简要总结
Chronic liver disease is a growing health concern, with limited access to liver transplants. This study addresses the urgent need for alternatives by exploring regenerative therapies, like G-CSF, to boost the liver's natural repair. The goal is to develop safe, effective, and accessible treatments for patients who cannot undergo transplant.
详细描述
The incidence of deaths from chronic liver diseases (CLD) and cirrhosis are rapidly increasing globally, including India. Liver transplant is the only curative option. Unfortunately, transplant is often not feasible. There is a need for nearly 100,000 liver transplants every year in India, though, only about 2,500 transplants are being done at present across the country. There is therefore, a huge unmet need of developing non-transplant options for chronic liver disease patients. In this regard emerging science of regenerative therapy holds great promises but therapeutic benefit of these therapies is limited due to lack of clinical validation.
Novelty: Cirrhosis as a result of hepatitis B and C can regress with effective antiviral therapy. Therapeutic options for patients with cryptogenic or alcoholic cirrhosis are, however, limited. With limited options for transplant. Liver failure is failure of regeneration hence, potentiating native liver repair and regeneration can serve as potential non-transplant approaches. Growth factors {like GCSF, darbepoetin (EPO) have shown survival benefits with improve liver repair and regeneration in clinical trials by us (Gastroenterology 2012, 2015, Liver Int. 2019; Hepatology 2021) and others, however the effect is transient. In the proposed National Collaborative Centre for Hepatic Regenerative Medicine (NC-CHRM) we will use this novel regenerative medicine approaches GCSF therapy (for management of chronic liver failure) to develop safe and effective regenerative therapy clinical protocol for transplant free management of liver failure in cirrhosis. Using integrated cellular, molecular and functional analysis we will also establish their mechanism of action and identify biomarker to access therapeutic response.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Early decompensated cirrhosis patients with MELD <16
排除标准
- •Patients with age less than 18 years or more than 65 years
- •Patients with Grade III ascites
- •CHILD C cirrhosis
- •Patients with a known focus of sepsis; spontaneous Bacterial Peritonitis (SBP)
- •variceal bleeding in past 3months
- •Hepatocellular Carcinoma (HCC) or other malignancy
- •Acute Kidney Injury (AKI) with serum Creatinine >1.5 mg/ dl, multi-organ failure, grade 3 or 4 Hepatic Encephalopathy (HE),
- •HIV seropositivity
- •Medically uncontrolled essential hypertension
- •Pregnancy
- •Viral etiology of liver disease
- •Co-existent Hepatitis B, Hepatitis C, HIV
- •Chronic kidney disease
- •Lack of informed consent
研究组 & 干预措施
Three cycles of GCSF+ darbepoetin and standard medical treatment
Patient randomize for Three cycle of GCSF+ darbepoetin together with standard medical treatment, G-CSF will be given at a dose of 5 μg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30 based on hematological response and darbepoetin will be given s/c at dose of 40mcg once a week (total 4 doses) for 1 month. Second cycle of GCSF+ darbepoetin will be given after 1 month of completion of first cycle that is at month 3 and third cycle will be given 1 month after completion of 2nd cycle that is at 5th month. All patients will receive the standard medical treatment.
干预措施: Gcsf (Drug)
Three cycles of GCSF+ darbepoetin and standard medical treatment
Patient randomize for Three cycle of GCSF+ darbepoetin together with standard medical treatment, G-CSF will be given at a dose of 5 μg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30 based on hematological response and darbepoetin will be given s/c at dose of 40mcg once a week (total 4 doses) for 1 month. Second cycle of GCSF+ darbepoetin will be given after 1 month of completion of first cycle that is at month 3 and third cycle will be given 1 month after completion of 2nd cycle that is at 5th month. All patients will receive the standard medical treatment.
干预措施: Darbepoetin (Drug)
Three cycles of GCSF+ darbepoetin and standard medical treatment
Patient randomize for Three cycle of GCSF+ darbepoetin together with standard medical treatment, G-CSF will be given at a dose of 5 μg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30 based on hematological response and darbepoetin will be given s/c at dose of 40mcg once a week (total 4 doses) for 1 month. Second cycle of GCSF+ darbepoetin will be given after 1 month of completion of first cycle that is at month 3 and third cycle will be given 1 month after completion of 2nd cycle that is at 5th month. All patients will receive the standard medical treatment.
干预措施: Standard Medical Treatment (Other)
Single cycle of GCSF+ darbepoetin and standard medical treatment
Patient randomize for Single cycle of GCSF+ darbepoetin together with standard medical treatment, G-CSF will be given at a dose of 5 μg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30 based on hematological response and darbepoetin will be given s/c at dose of 40mcg once a week (total 4 doses) for 1 month. All patients will receive the standard medical treatment.
干预措施: Gcsf (Drug)
Single cycle of GCSF+ darbepoetin and standard medical treatment
Patient randomize for Single cycle of GCSF+ darbepoetin together with standard medical treatment, G-CSF will be given at a dose of 5 μg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30 based on hematological response and darbepoetin will be given s/c at dose of 40mcg once a week (total 4 doses) for 1 month. All patients will receive the standard medical treatment.
干预措施: Darbepoetin (Drug)
Single cycle of GCSF+ darbepoetin and standard medical treatment
Patient randomize for Single cycle of GCSF+ darbepoetin together with standard medical treatment, G-CSF will be given at a dose of 5 μg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30 based on hematological response and darbepoetin will be given s/c at dose of 40mcg once a week (total 4 doses) for 1 month. All patients will receive the standard medical treatment.
干预措施: Standard Medical Treatment (Other)
结局指标
主要结局
Transplant-free survival of GCSF + darbepoetin in patients with early decompensated cirrhosis in both groups.
时间窗: 3 year
次要结局
- Transplant-free survival(6-month, one year, 2 year and 3 year)
- Improvement in liver disease severity indices, including the Child-Turcotte-Pugh (CTP) score (ΔCTP).(6-month, one year, 2 year and 3 year)
- Impact on liver injury (assessed by AST and ALT levels in blood).(6-month, one year, 2 year and 3 year)
- Impact on fibrosis (evaluated using Masson's Trichome stain and the Enhanced Liver Fibrosis [ELF] score).(6-month, one year, 2 year and 3 year)
- Proportion of patient developed new-onset of Liver Related Event (such as ascites, hepatic encephalopathy , acute kidney injury, bleed and sepsis) or show mortality in both the groups(6-month, one year, 2 year and 3 year)
- Cumulative incidence of sepsis, acute kidney injury or secondary organ dysfunction in both groups(6-month, one year, 2 year and 3 year)
- Cumulative incidence of second decompensation(6-month, one year, 2 year and 3 year)
- Improvement in liver disease severity indice like Model for End-Stage Liver Disease (MELD) score (ΔMELD).(6-month, one year, 2 year and 3 year)
- Proportion of patients completing treatment without major adverse effects(6-month, one year, 2 year and 3 year)
- Impact on regeneration (measured by plasma Alpha-Fetoprotein levels).(6-month, one year, 2 year and 3 year)
- Impact on bone marrow stem cell reserve (CD34⁺ cell count in peripheral blood)(One year, 2 year and 3 year)