G-CSF and Erythropoetin in Survival of Patients With Decompensated Liver Disease

Study Overview
=================
Brief Summary
-----------------
Study Design 50 patients will be enrolled and randomized into patients (Group IA) and controls (Group I B) Investigations: Hematology CBC, Prothrombin time and INR Peripheral smear, Retics Biochemistry Liver function testing, AFP Kidney function testing Etiology of chronic liver disease Infectious etiology: total antiHBc, anti HCV, HCV RNA, HBV DNA Non infectious etiology: Autoimmune markers, copper studies, iron studies, HOMA IR, FBS Etiology of decompensation Variceal bleed Infection ( blood culture, urine culture, sputum culture, chest xray) Surgery Drugs Alcohol intake Ascitic fluid analysis UGI endoscopy Imaging USG abdomen with Doppler for spleno-portal axis CECT- Triple phase upper abdomen Liver regenerative potential efficacy testing Histology ( by transjugular liver biopsy) Liver Dendritic cells ( CD11c, CD40, CD 54, CD 123, BDCA 2 staining) by flow cytometry CD 34+ cells, CD 45+ cells and CD 133+ cells measurement in hepatic venous blood, peripheral blood and liver biopsy by flow cytometry Markers of proliferation like Ki- 67, proliferating cell nuclear antigen (PCNA) in liver biopsy Markers of angiogenesis like VEGF, v WF in hepatic venous blood Measurement of Hepatic venous pressure gradient ( HVPG)

Official Title
-----------------
A Prospective Randomized Double Blind Trial to Study the Efficacy of G-CSF and Erythropoetin in Survival of Patients With Decompensated Liver Disease

Conditions
-----------------
Chronic Liver Disease

Intervention / Treatment
-----------------
* Drug: G-CSF+EPO
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients who were known to have cirrhosis of liver with portal hypertension, now decompensated with ascites/ jaundice/ bleed/ HE/ HRS Exclusion Criteria: Age <12 or > 75 years Autoimmune disorders HCC Sepsis ( Any culture positive: blood, urine, any other obvious source of infection: UTI, SBP) Multi organ failure Grade 4 HE HIV seropositivity / pregnancy Essential Hypertension Patients being taken up for transplant Refusal to participate in the study

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: G-CSF+EPO<br> | Drug: G-CSF+EPO<br>* Drug: Granulocyte Colony-stimulating Factor (G-CSF) and Erythropoetin (EPO) G-CSF (in prefilled syringe) at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every 3rd day till day 28 (total 12 doses), along with Darbopoetin alpha 100 mcg/ week (in prefilled syringe) for 4 weeks (total 4 doses). Arms: G-CSF+EPO Drug: Placebo Placebo 1 (in prefilled syringe) s/c at days 1, 2, 3, 4, 5 and then every 3rd day till day 28 (total 12 doses), along with Placebo 2 every week (in prefilled syringe) for 4 weeks (total 4 doses).<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo 1 (in prefilled syringe) s/c at days 1, 2, 3, 4, 5 and then every 3rd day till day 28 (total 12 doses), along with Placebo 2 every week (in prefilled syringe) for 4 weeks (total 4 doses).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| transplant free survival at 1 year |  | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| transplant free survival at 6 months, histo-pathological evidence of hepatic regeneration and mobilization of CD34/stem cells, improvement in severity assessment indices |  | 6 Months |