Efficacy of Granulocyte Colony-stimulating Factor and Erythropoetin for Patients With Acute-on-chronic Liver Failure
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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) |
- Transplant free survival at 3 months. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- 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 ]
| Estimated Enrollment: | 100 |
| Study Start Date: | July 2011 |
| Estimated Study Completion Date: | January 2013 |
| Estimated 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 |
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| Contact: Ankit Bhardwaj | 011-46300000 | bhardwaj.ankit3@gmail.com |
| India | |
| Institute of liver and Biliary Sciences | Recruiting |
| New Delhi, Delhi, India, 110070 | |
| Contact: Chandan Kumar, MD 011-46300000 <drchandankn@gmail.com>, | |
| Principal Investigator: Chandan Kumar, MD | |
| 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: | July 3, 2012 |
| 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 May 16, 2013