A Trial to Study the Influence of Growth Factors on Bone Marrow and Hepatic Regeneration in Patients With Decompensated Cirrhosis.

Study Overview
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Brief Summary
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This will be a randomized double blind study which will be conducted on patients admitted to Department of Hepatology from June 2013 to may 2014 at ILBS, New Delhi. Patients not having any exclusion criteria will undergo bone marrow examination and liver biopsy at the baseline. 60 patients of decompensated cirrhosis will be randomised into two limbs- limb A (30 patients) will receive G-CSF and erythropoietin while those on limb B (30 patients) will receive G-CSF alone. The drugs will be given for 2 months and patient will be followed for 1 year. G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every 3rd day till day 60 (total 22 doses). Erythropoietin will be given s/c at dose of 500 IU/Kg twice a week for 2 months. Follow up will be done on days 0,3,7,14,28, day 42 (6 weeks), day 60 (2 months), day 90 (3 months), day 180 (6 months), day 270 (9 months); and day 360 (1 year).

Conditions
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Decompensated Cirrhosis

Intervention / Treatment
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* Drug: G-CSF+Erythropoetin
* Drug: G-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 18-65 years All patients who are known to have cirrhosis of liver with portal hypertension and are compensated on presentation with no features of ascites/ jaundice/ bleed/ HE/ HRS. Only patients with alcoholic cirrhosis and cryptogenic cirrhosis (etiology work up negative) will be enrolled in the study. Exclusion Criteria: Sepsis ( Any culture positive: blood, urine, any other obvious source of infection: UTI, LRTI) Variceal bleed in the past 3 months Autoimmune disorders HCC (Hepatocellular Carcinoma) Multi organ failure Any features of decompensation in form of ascites/Jaundice/ HE (grade 3 or 4) / HRS HIV seropositivity Essential hypertension Pregnancy Refusal to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-CSF + Erythropoietin<br> | Drug: G-CSF<br> <br> |
| Active Comparator: G-CSF<br> | Drug: G-CSF+Erythropoetin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end point will be transplant free survival rate at 1 year in patients with decompensated cirrhosis. |  | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histopathological evidence of hepatic regeneration and mobilization of CD34/stem cells |  | 1 Year | 
| Histopathological evidence of contribution of bone marrow precursor cells in hepatic regeneration and the markers predicting positive response to growth factors |  | 1 Year | 
| Development of new complications such as appearance or worsening of hepatic encephalopathy, hepatorenal syndrome and sepsis. |  | 1 Year | 
| Improvement in severity assessment scores and safety profile of G-CSF (Growth-Colony Stimulating Factor) + EPO (Erythropoetin)dual therapy vs. G-CSF alone. |  | 1 Year | 
| Transplant free survival at 6 months in both groups |  | 6 months |