Clinical trial NCT00707785: Effect of Vitamin A in the Treatment of Neonatal Sepsis and Necrotizing Enterocolitis
Official title: Effect of Vitamin A in the Treatment of Sepsis and Necrotizing Enterocolitis in Hospitalized Neonates
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sepsis
Necrotizing Enterocolitis
Meningitis
Pneumonia
Keywords: vitamin A
Treatment
neonates
newborn
sepsis
necrotizing enterocolitis
meningitis
pneumonia
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: United States Agency for International Development (USAID)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2008-07-01
Enrollment: 424
Sex: ALL
Minimum age (years): 1
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease Mortality
timeFrame: prospective
Secondary outcomes:
measure: Inflammatory cytokine concentration
timeFrame: prospective
measure: Duration of inflammation
timeFrame: prospective
measure: Disease progression in NEC patients
timeFrame: prospective
Other outcomes:
measure: Treatment failure
timeFrame: prospective
measure: Time to recovery from severe illness
timeFrame: prospective
Locations:
city: Dhaka
country: Bangladesh
facility: Dhaka Shishu Hospital
Study officials:
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Christian L Coles, PhD
role: PRINCIPAL_INVESTIGATOR
References: