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

Phase 3

Completed

• Conditions: PELD; Severe Malnutrition; Liver Cirrhosis; Undernutrition
• Interventions: Drug: G-CSF (Filgrastim)

• Registration Number: NCT04113317
• Lead Sponsor: Fakultas Kedokteran Universitas Indonesia

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-09-22
• Study First Submitted QC: 2019-10-01
• Study First Posted: 2019-10-02
• Study Start: 2020-01-01
• Primary Completion: 2022-02-28
• Study Completion: 2022-02-28
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-26
• Last Update Posted: 2022-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group	G-CSF (Filgrastim)	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

Primary Outcome Measures

Name	Time	Method
PELD Score	90 days	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).
Anthropometric Changes	90 days	Measurement of mid-arm circumference (MAC) will be obtained in centimeters and be plotted on the curve to observe changes in nutritional status

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Fakultas Kedokteran Universitas Indonesia; 🇮🇩 Jakarta, Java, Indonesia