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

This study has been completed.
Sponsor:
Collaborators:
Bill and Melinda Gates Foundation
United States Agency for International Development (USAID)
Information provided by (Responsible Party):
Christian Coles, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00707785
First received: June 27, 2008
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Sepsis
Necrotizing Enterocolitis
Meningitis
Pneumonia
Dietary Supplement: Vitamin A
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Vitamin A in the Treatment of Sepsis and Necrotizing Enterocolitis in Hospitalized Neonates

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Disease Mortality [ Time Frame: prospective ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Inflammatory cytokine concentration [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • Duration of inflammation [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • Disease progression in NEC patients [ Time Frame: prospective ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Treatment failure [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • Time to recovery from severe illness [ Time Frame: prospective ] [ Designated as safety issue: No ]

Enrollment: 424
Study Start Date: December 2006
Study Completion Date: June 2012
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Sepsis - vitamin A
Dietary Supplement: Vitamin A
50,000 IU of Vitamin A 50,000 IU of vegetable oil
Other Name: Retinol
Placebo Comparator: 2
Sepsis - placebo
Dietary Supplement: Vitamin A
50,000 IU of Vitamin A 50,000 IU of vegetable oil
Other Name: Retinol
Experimental: 3
NEC - vitamin A
Dietary Supplement: Vitamin A
50,000 IU of Vitamin A 50,000 IU of vegetable oil
Other Name: Retinol
Placebo Comparator: 4
NEC - Placebo
Dietary Supplement: Vitamin A
50,000 IU of Vitamin A 50,000 IU of vegetable oil
Other Name: Retinol

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

Ages Eligible for Study:   up to 28 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00707785

Locations
Bangladesh
Dhaka Shishu Hospital
Dhaka, Bangladesh
Sponsors and Collaborators
Johns Hopkins University
Bill and Melinda Gates Foundation
United States Agency for International Development (USAID)
Investigators
Principal Investigator: Christian L Coles, PhD Johns Hopkins Bloomberg School of Public Health
  More Information

No publications provided

Responsible Party: Christian Coles, Assistant Professor, Department of International Health, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00707785     History of Changes
Other Study ID Numbers: H.22.05.12.20.A2, 1K01DK075478-01
Study First Received: June 27, 2008
Last Updated: September 24, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
vitamin A
Treatment
neonates
newborn
sepsis
necrotizing enterocolitis
meningitis
pneumonia

Additional relevant MeSH terms:
Enterocolitis
Meningitis
Pneumonia
Sepsis
Toxemia
Enterocolitis, Necrotizing
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Vitamin A
Vitamins
Retinol palmitate
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on July 26, 2014