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Efficacy of Granulocyte Colony-stimulating Factor and Erythropoetin for Patients With Acute-on-chronic Liver Failure

Primary Purpose

Acute on Chronic Hepatic Failure

Status
Completed
Phase
Phase 3
Locations
India
Study Type
Interventional
Intervention
Granulocyte Colony-stimulating Factor (G-CSF) and Erythropoetin (EPO)
Placebo
Sponsored by
Institute of Liver and Biliary Sciences, India
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute on Chronic Hepatic Failure focused on measuring Acute-on-chronic liver failure, ACLF, cirrhosis, acute hepatitis

Eligibility Criteria

12 Years - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

All consecutive patients with acute hepatic insult manifesting as jaundice (Sr. Bil. ≥ 5 mg/dL) and coagulopathy (INR≥1.5), complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease

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

Sites / Locations

  • Institute of liver and Biliary Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

G-CSF+EPO

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Transplant free survival at 3 months.

Secondary Outcome Measures

Transplant free survival at 6 months, histo-pathological evidence of hepatic regeneration and mobilization of CD34/stem cells, improvement in severity assessment indices

Full Information

First Posted
June 26, 2011
Last Updated
December 4, 2016
Sponsor
Institute of Liver and Biliary Sciences, India
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1. Study Identification

Unique Protocol Identification Number
NCT01383460
Brief Title
Efficacy of Granulocyte Colony-stimulating Factor and Erythropoetin for Patients With Acute-on-chronic Liver Failure
Official Title
Randomized Placebo-controlled Trial to Assess the Efficacy of Granulocyte Colony-stimulating Factor (G-CSF) and Erythropoetin (EPO) in the Survival of Patients With Acute-on-chronic Liver Failure (ACLF)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Liver and Biliary Sciences, India

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
50 patients of Acute-on-chronic liver failure (ACLF) will be enrolled and randomized into G-CSF+EPO or Placebo arms Treatment protocol To administer 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). Standard medical therapy included as per requirement lactulose, bowel wash, albumin, terlipressin, antibiotics (if indicated) will be continued and recorded. Pentoxiphylline in alcoholic hepatitis and Tenofovir in Hep B reactivation Controls: Standard medical therapy will be given along with placebo in similar prefilled syringes. Follow up Physical examination will be done daily, after 1 week and at 4 weeks, at 2 months, at 3 months and at 6 months CBC on alternate day for 1 week, at end of 1 week and then at end of 4 weeks , at 2 months, at 3 months and at 6 months KFT on alternate day for 1 week, at end of 1 week and then at end of 4 weeks, at 2 months, at 3 months and at 6 months LFT along with PT/INR on alternate day for 1 week, at end of 1 week and then at end of 4 weeks, at 2 months, at 3 months and at 6 months AFP at baseline, after 4 weeks, at 3 months and at 6 months Liver regenerative potential efficacy testing at baseline and after 4 weeks
Detailed Description
50 patients of ACLF will be enrolled and randomized into G-CSF+EPO or Placebo arms Baseline investigations: Hematology CBC, Prothrombin time and INR Peripheral smear, Retics Biochemistry Liver function testing, AFP Kidney function test Etiology of acute event: Infectious etiology: IgM anti HAV, IgM anti HEV, IgM anti HBc ( If HBsAg +ve), IgM anti HDV ( If HBsAg +ve), HEV RNA Non Infectious etiology: Alcohol binging in last 4 weeks, hepatotoxic drugs, ANA (>1: 80), IgG , surgeries in past 4 weeks, acute variceal bleed within 4 weeks Etiology of underlying 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 Ascitic fluid analysis ( wherever its possible) UGI endoscopy Imaging USG abdomen with Doppler for spleno-portal axis CECT- Triple phase upper abdomen Liver regenerative potential efficacy testing (wherever it is possible) Histology ( by transjugular liver biopsy) Liver Dendritic cells ( CD11c, CD40, CD 54, CD 123, BDCA 2 staining) by flow cytometry CD 34+ 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 hepatic venous blood and liver biopsy Markers of angiogenesis like VEGF, v WF in hepatic venous blood Measurement of Hepatic venous pressure gradient ( HVPG) Treatment protocol To administer 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). Standard medical therapy included as per requirement lactulose, bowel wash, albumin, terlipressin, antibiotics (if indicated) will be continued and recorded. Pentoxiphylline in alcoholic hepatitis and Tenofovir in Hep B reactivation Controls: Standard medical therapy will be given along with placebo in similar prefilled syringes. Follow up Physical examination will be done daily, after 1 week and at 4 weeks, at 2 months, at 3 months and at 6 months CBC on alternate day for 1 week, at end of 1 week and then at end of 4 weeks , at 2 months, at 3 months and at 6 months KFT on alternate day for 1 week, at end of 1 week and then at end of 4 weeks, at 2 months, at 3 months and at 6 months LFT along with PT/INR on alternate day for 1 week, at end of 1 week and then at end of 4 weeks, at 2 months, at 3 months and at 6 months AFP at baseline, after 4 weeks, at 3 months and at 6 months Liver regenerative potential efficacy testing at baseline and after 4 weeks

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute on Chronic Hepatic Failure
Keywords
Acute-on-chronic liver failure, ACLF, cirrhosis, acute hepatitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
G-CSF+EPO
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Granulocyte Colony-stimulating Factor (G-CSF) and Erythropoetin (EPO)
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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).
Primary Outcome Measure Information:
Title
Transplant free survival at 3 months.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Transplant free survival at 6 months, histo-pathological evidence of hepatic regeneration and mobilization of CD34/stem cells, improvement in severity assessment indices
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All consecutive patients with acute hepatic insult manifesting as jaundice (Sr. Bil. ≥ 5 mg/dL) and coagulopathy (INR≥1.5), complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shiv Kumar Sarin, MD, DM
Organizational Affiliation
Institute of Liver and Biliary Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Institute of liver and Biliary Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110070
Country
India

12. IPD Sharing Statement

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Efficacy of Granulocyte Colony-stimulating Factor and Erythropoetin for Patients With Acute-on-chronic Liver Failure

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