Granulocyte-Colony Stimulating Factor (G-CSF) as Optimizing Therapy for Pediatric Liver Transplantation

Study Overview
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Brief Summary
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This study compares the effect of human recombinant Granulocyte-Colony Stimulating Factor (G-CSF) in pediatric patients with liver cirrhosis with a control group. The study aims to observe improvement of (Pediatric End-stage Liver Disease) PELD score and nutritional status prior to liver transplantation procedure. In addition to the intervention, standard treatments for liver cirrhosis are also given for both groups. G-CSF is administered for 12 times. Condition of disease: Pediatric patient aged 3 months to 12 years old Liver cirrhosis Undernourished / Severe malnutrition PELD score 10-25 Intervention: Drug: Recombinant Human G-CSF Phase: Phase 3

Detailed Description
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This open-label randomized control trial conducted in Cipto Mangunkusumo Hospital, Jakarta, Indonesia, aimed to determine the effect of G-CSF to improve PELD score and nutritional status of pediatric patients with liver cirrhosis prior to liver transplantation. A total of 52 pediatric patients with liver cirrhosis, malnutrition and PELD score between 10-25 will be collected and divided into intervention group and control group. The intervention group will be given a subcutaneous injection of G-CSF 5μg/kg/day for 5 days consecutively, followed by a single dose every 3 days up to 12 times throughout the trial. Additionally, both the intervention and control group receive standard liver cirrhosis treatment. Randomization is done using block randomization. The patients will be clinically monitored and evaluated for anthropometric changes (body weight, mid-arm circumference, mid-arm muscle circumference, and triceps skinfold thickness), complete blood count, absolute neutrophil count, liver function tests, cytokines (IL-10, TNF-α), Procalcitonin, hepatocyte growth factor (HGF), CD34+ cell count and PELD score (albumin, bilirubin, prothrombin and international normalized ratio values). Data analysis will be performed using IBM SPSS Statistics version 20.0.0.

Official Title
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The Role of Granulocyte-Colony Stimulating Factor (G-CSF) for Improving PELD Score and Nutritional Status in Pediatric Liver Cirrhosis Prior to Liver Transplantation Through Immunomodulation of Neutrophil, CD34+ Cell, TNF-α and IL-10

Conditions
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Liver Cirrhosis, Severe Malnutrition, PELD, Undernutrition

Intervention / Treatment
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* Drug: G-CSF (Filgrastim)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 3 months to 12 years old Conscious state Without the presence of fever (temperature: <37,5°C) Decompensated liver cirrhosis Liver cirrhosis due to various etiology Undernourished or severe malnutrition PELD score between 10-25 Exclusion Criteria: Malignancy (liver origin or other types) History of undergoing any organ transplantation procedure Acute liver failure Failure of any organ other than the liver Encephalopathy Severe infection such as bacterial peritonitis and pneumonia

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 12 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Subcutaneous injection of G-CSF with dose of 5μg/kg/day for 5 days consecutively, in addition to a single dose every 3 days up to 12 times, as well as liver cirrhosis standard regimen | Drug: G-CSF (Filgrastim)<br>* Contains 0,59 mg of acetate, 0,04 mg of polysorbate 80, 0,035 mg of sodium, 50 mg of sorbitol<br>* Other names: Neupogen;|
| No Intervention: Control Group<br>Liver cirrhosis standard treatment only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PELD Score | The scoring determines the individual's need for liver transplant. Calculation is based on an equation that incorporates the values of bilirubin serum, international normalized ratio, albumin and body growth measurement. Score ranges between 6 (low illness level) to 40 (severely ill). | 90 days | 
| Anthropometric Changes | Measurement of mid-arm circumference (MAC) will be obtained in centimeters and be plotted on the curve to observe changes in nutritional status | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pro-inflammatory Marker | Tumor necrosis factor alpha (TNF-α) cytokine level in the blood will be the parameter for pro-inflammatory marker | 30 days | 
| Anti-inflammatory Marker | Interleukin-10 (IL-10) cytokine level in the blood will be the parameter for anti-inflammatory marker | 30 days | 
| Liver Regeneration Marker | hepatocyte growth factor (HGF) serum level will be the biochemical parameter for liver regeneration | 30 days |