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

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

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.

Study Overview

• Status: Completed
• Conditions: Pneumonia; Sepsis; Necrotizing Enterocolitis; Meningitis
• Intervention / Treatment: Dietary supplement: Vitamin A

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.

• Study Type: Interventional
• Enrollment (Actual): 424
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • Dhaka Shishu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 4 weeks (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Sepsis - vitamin A	Dietary supplement: Vitamin A; 50,000 IU of Vitamin A 50,000 IU of vegetable oil; Other Names: Retinol
PLACEBO_COMPARATOR: 2; Sepsis - placebo	Dietary supplement: Vitamin A; 50,000 IU of Vitamin A 50,000 IU of vegetable oil; Other Names: Retinol
EXPERIMENTAL: 3; NEC - vitamin A	Dietary supplement: Vitamin A; 50,000 IU of Vitamin A 50,000 IU of vegetable oil; Other Names: Retinol
PLACEBO_COMPARATOR: 4; NEC - Placebo	Dietary supplement: Vitamin A; 50,000 IU of Vitamin A 50,000 IU of vegetable oil; Other Names: Retinol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease Mortality	prospective

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Time Frame
Treatment failure	prospective
Time to recovery from severe illness	prospective

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); United States Agency for International Development (USAID); Bill and Melinda Gates Foundation
• Investigators: Principal Investigator: Christian L Coles, PhD, Johns Hopkins Bloomberg School of Public Health

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (ACTUAL): April 1, 2011
• Study Completion (ACTUAL): June 1, 2012

Study Registration Dates

• First Submitted: June 27, 2008
• First Submitted That Met QC Criteria: June 27, 2008
• First Posted (ESTIMATE): July 1, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): September 25, 2013
• Last Update Submitted That Met QC Criteria: September 24, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Treatment; pneumonia; sepsis; meningitis; neonates; newborn; necrotizing enterocolitis; vitamin A
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Sepsis; Toxemia; Pneumonia; Enterocolitis; Enterocolitis, Necrotizing; Meningitis; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin A
• Other Study ID Numbers: H.22.05.12.20.A2; 1K01DK075478-01 (NIH)