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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Institute of Liver and Biliary Sciences, India
ClinicalTrials.gov Identifier:
NCT01383460
First received: June 26, 2011
Last updated: April 2, 2014
Last verified: July 2012
  Purpose

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


Condition Intervention Phase
Acute on Chronic Hepatic Failure
Drug: Granulocyte Colony-stimulating Factor (G-CSF) and Erythropoetin (EPO)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Institute of Liver and Biliary Sciences, India:

Primary Outcome Measures:
  • Transplant free survival at 3 months. [ Time Frame: 3 months ] [ Designated as safety issue: No ]

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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 55
Study Start Date: July 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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).
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).

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

  Eligibility

Ages Eligible for Study:   12 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01383460

Locations
India
Institute of liver and Biliary Sciences
New Delhi, Delhi, India, 110070
Sponsors and Collaborators
Institute of Liver and Biliary Sciences, India
Investigators
Study Director: Shiv K Sarin, MD, DM Institute of Liver & Biliary Sciences (ILBS)
  More Information

No publications provided

Responsible Party: Institute of Liver and Biliary Sciences, India
ClinicalTrials.gov Identifier: NCT01383460     History of Changes
Other Study ID Numbers: ILBS ACLF 01
Study First Received: June 26, 2011
Last Updated: April 2, 2014
Health Authority: India: Ministry of Health

Keywords provided by Institute of Liver and Biliary Sciences, India:
Acute-on-chronic liver failure
ACLF
cirrhosis
acute hepatitis

Additional relevant MeSH terms:
Liver Failure
Liver Failure, Acute
End Stage Liver Disease
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Epoetin Alfa
Lenograstim
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2014