Enteral Granulocyte Colony Stimulating Factor and Erythropoietin Early in Life Increases Feeding Tolerance in Preterm Infants: A Randomized Controlled Trial

Study Overview
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Brief Summary
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With preterm birth, the ingestion of amniotic fluid containing enterocyte trophic factors ceases abruptly. This likely predisposes them to villous atrophy feeding intolerance and necrotizing enterocolitis(NEC) once feedings are instituted.Granulocyte Colony-Stimulating Factor (G-CSF) and Erythropoietin (EPO) have important non-hematopoietic roles in human developmental biology. Among these roles, they have trophic actions on villous height and bowel length of the developing intestine.The aim of this study is to evaluate the efficacy of enteral recombinant human G-CSF and recombinant human EPO in prevention of feeding intolerance and /or NEC in preterm infants.

Conditions
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Feeding Intolerance, Necrotizing Enterocolitis

Intervention / Treatment
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* Drug: recombinant human G-CSF, and rhEPO
* Drug: rh G-CSF
* Drug: rh EPO
* Drug: rh G-GSF and rh EPO together
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: premature neonates < 33 weeks gestational age Exclusion Criteria: major congenital anomalies prior use of cytokines

Ages Eligible for Study
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Maximum Age: 1 Month

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-CSF<br> | Drug: rh G-CSF<br>* Dosage: 4.5 µg/ kg (diluted into 1 ml distilled water) administered once daily by an orogastric tube till the enteral intake reached 100 mL/kg of milk, or after a maximum of seven days.<br>|
| Experimental: EPO<br> | Drug: rh EPO<br>* Dosage: 88 IU/ kg once daily (diluted into 1 ml distilled water) administered by an orogastric tube till the enteral intake reached 100 mL/kg of milk, or after a maximum of seven days.<br>|
| Experimental: G-CSF and EPO<br> | Drug: recombinant human G-CSF, and rhEPO<br>* G-CSF 4.5 microgram /kg/day enteral EPO 88 mIU/kg/day enteral<br>Drug: rh G-GSF and rh EPO together<br>* EPO dosage: 88 IU/ kg once daily i.e 88000 mU/kg/day (diluted into 1 ml distilled water) administered by an orogastric tube till the enteral intake reached 100 mL/kg of milk, or after a maximum of seven days.G-CSF dosage: 4.5 µg/ kg (diluted into 1 ml distilled water) administered once daily by an orogastric tube till the enteral intake reached 100 mL/kg of milk, or after a maximum of seven days.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* distilled water :1 ml distilled water administered by an orogastric tube till the enteral intake reached 100 mL/kg of milk, or after a maximum of seven days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The times taken to establish quarter, half, three quarters, and full enteral feeding after the drug treatment (at least 150ml/kg/day). |  | one month | 
| Time to stop parentral nutrition |  | one month | 
| Day of onset of weight gain |  | one month | 
| Duration of hospitalization |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Necrotizing enterocolitis (NEC)stage (if any) | Bell and colleagues proposed a clinical staging system for NEC: infants with suspected NEC (stage I), definite NEC (stage II), or advanced NEC (stage III) (Bell et al., 1978). | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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feeding intolerance, recombinant growth factors, G-CSF, EPO, necrotizing enterocolitis