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

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

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)

Study Overview

• Status: Completed
• Conditions: Chronic Liver Disease
• Intervention / Treatment: Drug: Placebo; Drug: G-CSF+EPO

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of liver and Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	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).
Active Comparator: G-CSF+EPO	Drug: G-CSF+EPO; 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).

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Publications and helpful links

General Publications

• Kedarisetty CK, Anand L, Bhardwaj A, Bhadoria AS, Kumar G, Vyas AK, David P, Trehanpati N, Rastogi A, Bihari C, Maiwall R, Garg HK, Vashishtha C, Kumar M, Bhatia V, Sarin SK. Combination of granulocyte colony-stimulating factor and erythropoietin improves outcomes of patients with decompensated cirrhosis. Gastroenterology. 2015 Jun;148(7):1362-70.e7. doi: 10.1053/j.gastro.2015.02.054. Epub 2015 Mar 4.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: June 28, 2011
• First Submitted That Met QC Criteria: June 28, 2011
• First Posted (Estimate): June 29, 2011

Study Record Updates

• Last Update Posted (Estimate): July 31, 2013
• Last Update Submitted That Met QC Criteria: July 30, 2013
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: ILBS DLD 01