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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01383460
First Posted: June 28, 2011
Last Update Posted: December 6, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Institute of Liver and Biliary Sciences, India
  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
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
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 ]

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 ]

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

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 Kumar Sarin, MD, DM Institute of Liver and Biliary Sciences
  More Information

Responsible Party: Institute of Liver and Biliary Sciences, India
ClinicalTrials.gov Identifier: NCT01383460     History of Changes
Other Study ID Numbers: ILBS ACLF 01
First Submitted: June 26, 2011
First Posted: June 28, 2011
Last Update Posted: December 6, 2016
Last Verified: July 2012

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
End Stage Liver Disease
Acute-On-Chronic Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Liver Failure, Acute
Lenograstim
Epoetin Alfa
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Hematinics