Effect of Vitamin A in the Treatment of Neonatal Sepsis and Necrotizing Enterocolitis

Study Overview
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Brief Summary
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The purpose of the study is to determine whether vitamin A can improve survival and facilitate recovery from sepsis and necrotizing enterocolitis in hospitalized neonates.

Detailed Description
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Sepsis and necrotizing enterocolitis (NEC) are leading causes of morbidity and mortality in neonates. Studies have shown that early reversal of the signs associated with severe disease is an important prognostic factor during acute illness. Vitamin A deficiency is widespread among children, including neonates, in developing countries. Vitamin A plays an important role in mediating immune responses and in maintaining epithelial integrity. For this reason vitamin A supplementation during the acute phase of neonatal infection could work synergistically with present antibiotic regimens in promoting early reversal of signs associated with adverse outcome and shorten the total duration of clinical illness. The purpose of the proposed hospital-based clinical trial is to evaluate the efficacy of vitamin A supplementation on reducing the morbidity and mortality among neonates hospitalized with sepsis (n=366) and NEC(n=150). Enrolled subjects will be randomized at the time of hospitalization to receive one dose of either 50,000 IU of vitamin A or placebo at enrollment, in addition to standard antibiotic therapy. We will compare the proportion of treatment failures in sepsis patients, the frequency of disease progression and mortality in NEC patients, and the time to clinical recovery and discharge between treatment groups. In addition, the study will determine whether vitamin A reduces pro-inflammatory cytokine levels; elevated host inflammatory cytokines are thought to contribute to the severity of both conditions. If vitamin A is found to be efficacious in the treatment of sepsis and NEC it could present a needed cost-effective approach to decreasing the global morbidity, mortality and the economic cost associated with neonatal sepsis and NEC in the developing world.

Official Title
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Effect of Vitamin A in the Treatment of Sepsis and Necrotizing Enterocolitis in Hospitalized Neonates

Conditions
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Sepsis, Necrotizing Enterocolitis, Meningitis, Pneumonia

Intervention / Treatment
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* Dietary Supplement: Vitamin A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newborns less than 29 days with clinical sepsis Exclusion Criteria: healthy infants major congenital abnormalities known inborn error(s) of metabolism chronic disorders of other organs (e.g. cholestasis) definite or severe NEC (> stage 2) congenital heart disease Infants receiving VA supplements Infants requiring mechanical ventilation Infant is unconscious

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 28 Days

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Sepsis - vitamin A | Dietary Supplement: Vitamin A<br>* 50,000 IU of Vitamin A 50,000 IU of vegetable oil<br>* Other names: Retinol;|
| Placebo Comparator: 2<br>Sepsis - placebo | Dietary Supplement: Vitamin A<br>* 50,000 IU of Vitamin A 50,000 IU of vegetable oil<br>* Other names: Retinol;|
| Experimental: 3<br>NEC - vitamin A | Dietary Supplement: Vitamin A<br>* 50,000 IU of Vitamin A 50,000 IU of vegetable oil<br>* Other names: Retinol;|
| Placebo Comparator: 4<br>NEC - Placebo | Dietary Supplement: Vitamin A<br>* 50,000 IU of Vitamin A 50,000 IU of vegetable oil<br>* Other names: Retinol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Mortality |  | prospective | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory cytokine concentration |  | prospective | 
| Duration of inflammation |  | prospective | 
| Disease progression in NEC patients |  | prospective | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumonia, vitamin A, Treatment, neonates, newborn, sepsis, necrotizing enterocolitis, meningitis