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

Liver Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04113317
• Other study ID #: FakultasKUI
• Status: Completed
• Phase: Phase 3
• Start date: January 1, 2020
• Est. completion date: February 28, 2022

Study information

• Verified date: July 2022
• Source: Fakultas Kedokteran Universitas Indonesia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: February 28, 2022
• Est. primary completion date: February 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis
• Malnutrition
• PELD
• Severe Malnutrition
• Undernutrition

Intervention

Drug:
• G-CSF (Filgrastim)
Contains 0,59 mg of acetate, 0,04 mg of polysorbate 80, 0,035 mg of sodium, 50 mg of sorbitol

Locations

Country	Name	City	State
Indonesia	Fakultas Kedokteran Universitas Indonesia	Jakarta	Java

Sponsors (2)

Lead Sponsor	Collaborator
Fakultas Kedokteran Universitas Indonesia	Dr Cipto Mangunkusumo General Hospital

Country where clinical trial is conducted

Indonesia, 

References & Publications (5)

Chavez-Tapia NC, Mendiola-Pastrana I, Ornelas-Arroyo VJ, Noreña-Herrera C, Vidaña-Perez D, Delgado-Sanchez G, Uribe M, Barrientos-Gutierrez T. Granulocyte-colony stimulating factor for acute-on-chronic liver failure: systematic review and meta-analysis. Ann Hepatol. 2015 Sep-Oct;14(5):631-41. Review. — View Citation

Dale DC, Crawford J, Klippel Z, Reiner M, Osslund T, Fan E, Morrow PK, Allcott K, Lyman GH. A systematic literature review of the efficacy, effectiveness, and safety of filgrastim. Support Care Cancer. 2018 Jan;26(1):7-20. doi: 10.1007/s00520-017-3854-x. Epub 2017 Sep 22. Review. — View Citation

Fioredda F, Lanza T, Gallicola F, Riccardi F, Lanciotti M, Mastrodicasa E, Signa S, Zanardi S, Calvillo M, Dufour C. Long-term use of pegfilgrastim in children with severe congenital neutropenia: clinical and pharmacokinetic data. Blood. 2016 Oct 27;128(17):2178-2181. Epub 2016 Sep 12. — View Citation

Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma BC, Sakhuja P, Sarin SK. Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology. 2012 Mar;142(3):505-512.e1. doi: 10.1053/j.gastro.2011.11.027. Epub 2011 Nov 23. — View Citation

Yang Q, Yang Y, Shi Y, Lv F, He J, Chen Z. Effects of Granulocyte Colony-Stimulating Factor on Patients with Liver Failure: a Meta-Analysis. J Clin Transl Hepatol. 2016 Jun 28;4(2):90-6. doi: 10.14218/JCTH.2016.00012. Epub 2016 Jun 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Pro-inflammatory Marker	Tumor necrosis factor alpha (TNF-a) cytokine level in the blood will be the parameter for pro-inflammatory marker	30 days
Secondary	Anti-inflammatory Marker	Interleukin-10 (IL-10) cytokine level in the blood will be the parameter for anti-inflammatory marker	30 days
Secondary	Liver Regeneration Marker	hepatocyte growth factor (HGF) serum level will be the biochemical parameter for liver regeneration	30 days