Glutamine Supplementation to Prevent Death or Infection in Extremely Premature Infants

Study Overview
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Brief Summary
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This large multicenter double-masked clinical trial tested whether supplementation of standard neonatal parenteral nutrition with glutamine would reduce the risk of death or late-onset sepsis in extremely-low-birth-weight (ELBW, less than or equal to 1000 gm) infants. Neonates with birth weights of 401-1000gm were randomized to standard TrophAmine or TrophAmine supplemented with glutamine before 72 hours and continued until the infants are tolerating full enteral feedings.

Detailed Description
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Meeting the protein and energy requirements of extremely premature infants in early postnatal life requires early hyperalimentation and the gradual introduction of enteral feedings. Glutamine, which is the most abundant amino acid in the human body and taken up in greatest quantity by the fetus from the placenta, is not routinely provided in neonatal parenteral nutrition preparations. This large multicenter double-masked clinical trial tested whether supplementation of standard neonatal parenteral nutrition with glutamine would reduce the risk of death or late-onset sepsis in extremely-low-birth-weight (ELBW, less than or equal to 1000 gm) infants. Neonates with birth weights of 401-1000gm were randomized to standard TrophAmine or TrophAmine supplemented with glutamine before 72 hours and continued until the infants are tolerating full enteral feedings. Infants received a neurodevelopmental assessment by masked, certified examiners at 18-22 months postmenstrual age.

Official Title
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Randomized Controlled Trial of Parenteral Glutamine Supplementation for Extremely-Low-Birth-Weight (ELBW) Infants

Conditions
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Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Sepsis

Intervention / Treatment
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* Drug: Glutamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 401-1000 gm More than 12 hrs and less than 72 hrs after birth; intravenous access Parental consent Exclusion Criteria: One or more major congenital anomalies Infants meeting criteria for terminal illness Congenital nonbacterial infection with overt signs at birth

Ages Eligible for Study
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Maximum Age: 72 Hours

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glutamine<br>TrophAmine (B. Braun/McGaw) with cysteine hydrochloride (40mg/gm amino acids) with L-glutamine added (20% of the total amount of amino acids) | Drug: Glutamine<br>* Infants randomized to glutamine supplementation will receive glutamine any time that parenteral nutrition is required during the first 120 days of hospitalization.<br>* Other names: TrophAmine;|
| Placebo Comparator: Placebo<br>Standard TrophAmine (B. Braun/McGaw) with cysteine hydrochloride (40mg/gm amino acids) | Drug: Placebo<br>* TrophAmine given any time that parenteral nutrition is required during the first 120 days of hospitalization.<br>* Other names: TrophAmine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or late-onset sepsis |  | At hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance of enteral feeding (number of days to reach full enteral feeds) and decrease number of episodes of feeding intolerance |  | At hospital discharge | 
| Necrotizing Enterocolitis |  | At hospital discharge | 
| Episodes of late-onset sepsis |  | At hospital discharge | 
| Growth (days to reach 1500 grams) |  | At hospital discharge | 
| Number of days on parenteral nutrition |  | At hospital discharge | 
| Length of stay in NICU |  | At hospital discharge | 
| Neurodevelopmental outcome |  | 18-22 months corrrected age | 
| Levels of pro-inflammatory cytokines |  | In the perinatal period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW) infants, Prematurity, Glutamine, Total parenteral nutrition, Nutrition, Very low birth weight (VLBW) infants