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

NCT01383460 | Completed Phase 3

• 1 other identifier: ILBS ACLF 01
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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

Conditions

Acute on Chronic Hepatic Failure

Keywords

Acute-on-chronic liver failure; ACLF; cirrhosis; acute hepatitis

Outcome Measures

Primary Outcomes (1)

• Transplant free survival at 3 months.

  3 months

Secondary Outcomes (1)

• 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

Study Arms (2)

G-CSF+EPO

ACTIVE COMPARATOR

Drug: Granulocyte Colony-stimulating Factor (G-CSF) and Erythropoetin (EPO)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Granulocyte Colony-stimulating Factor (G-CSF) and Erythropoetin (EPO) DRUG

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).

G-CSF+EPO

Placebo DRUG

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).

Placebo

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of liver and Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure; Fibrosis

Interventions

Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Shiv Kumar Sarin, MD, DM

  Institute of Liver and Biliary Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2011
• First Posted: June 28, 2011
• Study Start: July 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: December 6, 2016

Record last verified: 2012-07

Locations

IN (1)