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

Johns Hopkins University

Status and phase: Completed; Phase 3

Conditions: Meningitis; Necrotizing Enterocolitis; Pneumonia; Sepsis

Treatments: Dietary Supplement: Vitamin A

Study type: Interventional

Funder types: Other; Other U.S. Federal agency; NIH

Identifiers

NCT00707785

1K01DK075478-01 (U.S. NIH Grant/Contract)

H.22.05.12.20.A2

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 424 patients

Sex: All

Ages: 1 to 28 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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424 participants in 4 patient groups, including a placebo group

1

Experimental group

Description:

Sepsis - vitamin A

Treatment:

Dietary Supplement: Vitamin A

2

Placebo Comparator group

Description:

Sepsis - placebo

Treatment:

Dietary Supplement: Vitamin A

3

Experimental group

Description:

NEC - vitamin A

Treatment:

Dietary Supplement: Vitamin A

4

Placebo Comparator group

Description:

NEC - Placebo

Treatment:

Dietary Supplement: Vitamin A