To Assess the Efficacy of High-Volume Plasma Exchange and GCSF Versus GCSF Alone in Patients of Acute on Chronic Liver Failure (ACLF).

Study Overview
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Brief Summary
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Study design-Open label randomized controlled trial Study period-2 years Study population-All patients of ACLF admitted to ILBS for a period of two years from Feb 2017 to Dec 2018 All the patients of ACLF will receive standard medical therapy and will be randomized within 48 hours of admission into three groups after screening for exclusion and inclusion criteria.(1:2:2) Group A-Standard Medical Therapy only Group B-Standard Medical therapy + Plasma exchange + GCSF Group C-Standard Medical Therapy + GCSF

Official Title
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To Assess the Efficacy of High-Volume Plasma Exchange and GCSF Versus GCSF Alone in Patients of Acute on Chronic Liver Failure (ACLF)-A Randomized Controlled Trial.

Conditions
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Acute-On-Chronic Liver Failure

Intervention / Treatment
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* Drug: Standard Medical Therapy
* Biological: Plasma Exchange
* Biological: GCSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - All consecutive patients in age group of 18-70 years with acute on chronic liver failure as defined by APASL criteria shall be included in the study.Only those patients who wish to be enrolled in the trial shall be included in the study. Exclusion Criteria: Steroid eligible patients with severe alcoholic hepatitis Cirrhosis of liver with previous history of decompensation Patients with severe cardiopulmonary disease Pregnancy Human Immmunodeficiency Virus infection Hepatocellular carcinoma or extrahepatic malignancy Chronic renal insufficiency on treatment with haemodialysis Uncontrolled bleed or patients in disseminated intravascular coagulopathy Patient with expected survival of less than 48 hours Patients with moderate-severe acute respiratory distress syndrome Hemodynamic instability with noradrenaline requirement of more than >0.5ug/kg/min or requirement of dual vasopressors Patients with leukemoid reaction or total leucocyte count > 40,000/mm3 Patients diagnosed with Hemophagocytic Lymphohistiocytosis Patients with known hypersensitivity to Granulocyte colony stimulating factor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Medical Therapy<br>The patients in group A will be given standard medical therapy only as per requirement. Lactulose, bowel wash, albumin, terlipressin, antibiotics and anti-virals in hepatitis B reactivation will be continued and recorded. | Drug: Standard Medical Therapy<br>* The patients in group A will be given standard medical therapy only as per requirement. Lactulose, bowel wash, albumin, terlipressin, antibiotics and anti-virals in hepatitis B reactivation will be continued and recorded.<br>|
| Experimental: Standard Medical Therapy + Plasma exchange + GCSF<br>The patients in group B shall be given GCSF in a dose of 5 ug/kg/day on day 1,2,3,4,5 followed by every 3rd day till day 28 along with alternate day high volume plasma exchange sessions till a maximum of ten sessions. | Drug: Standard Medical Therapy<br>* The patients in group A will be given standard medical therapy only as per requirement. Lactulose, bowel wash, albumin, terlipressin, antibiotics and anti-virals in hepatitis B reactivation will be continued and recorded.<br>Biological: Plasma Exchange<br>* High volume plasma exchange sessions till a maximum of ten sessions.<br>Biological: GCSF<br>* The GCSF in a dose of 5 ug/kg/day on day 1,2,3,4,5 followed by every 3rd day till day 28<br>|
| Experimental: Standard Medical Therapy + GCSF<br>The patients in this will be given standard medical therapy only as per requirement. Lactulose, bowel wash, albumin, terlipressin, antibiotics and anti-virals in hepatitis B reactivation will be continued and recorded. The GCSF in a dose of 5 ug/kg/day on day 1,2,3,4,5 followed by every 3rd day till day 28 | Drug: Standard Medical Therapy<br>* The patients in group A will be given standard medical therapy only as per requirement. Lactulose, bowel wash, albumin, terlipressin, antibiotics and anti-virals in hepatitis B reactivation will be continued and recorded.<br>Biological: GCSF<br>* The GCSF in a dose of 5 ug/kg/day on day 1,2,3,4,5 followed by every 3rd day till day 28<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant free survival |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in biochemical parameter which is defined as > 20% reduction from baseline in both groups |  | Day 14 | 
| Improvement in biochemical parameter which is defined as > 20% reduction from baseline in both groups |  | Day 28 | 
| Improvement in clinical parameters which is defined as > 20% reduction from baseline in both groups |  | Day 14 | 
| Improvement in clinical parameters which is defined as > 20% reduction from baseline in both groups |  | Day 28 | 
| Improvement in APACHEII (by 2 points ) |  | 2 years | 
| Improvement in MELD (by 2 points ) |  | 2 years | 
| Improvement in SIRS by 2 points |  | 2 years | 
| Improvement in SOFA (by 2 points ) |  | 2 years | 
| Incidence of new onset sepsis and SIRS in both groups. |  | Day 28 | 
| Side effects of therapy in both groups |  | 2 years |