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
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
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
NCT ID
NCT01383460
First Posted
June 26, 2011
Last Updated
December 4, 2016
Sponsor
Institute of Liver and Biliary Sciences, India
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
Learn more about this trial
Efficacy of Granulocyte Colony-stimulating Factor and Erythropoetin for Patients With Acute-on-chronic Liver Failure
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