Vitamin A Supplementation for Extremely-Low-Birth-Weight Infants

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01203488
First received: September 15, 2010
Last updated: January 9, 2011
Last verified: September 2010
  Purpose

This multi-site, randomized trial was conducted to determine the safety and effectiveness of a higher dose of vitamin A and determine if this would increase the rate of survival without bronchopulmonary dysplasia (BPD) and reduce the risk of sepsis. Infants with birth weights from 401-1000g and who were on mechanical ventilation or supplemental oxygen at 24-96 hours of age were enrolled. Subjects were randomized to either the Vitamin A or a control group. Infants in the Vitamin A group were given a dose of 5000 IU (0.1 ml) intramuscularly on Mondays, Wednesdays, and Fridays for four weeks. Control infants received a sham procedure rather than placebo injections.


Condition Intervention Phase
Infant, Newborn
Infant, Low Birth Weight
Infant, Small for Gestational Age
Infant, Premature
Bronchopulmonary Dysplasia
Respiration, Artificial
Respiratory Distress Syndrome, Newborn
Sepsis
Drug: Vitamin A
Other: Sham Procedure
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized Trial of Vitamin A Supplementation for Extremely-Low-Birth-Weight

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Chronic lung disease or death [ Time Frame: 36 weeks' postmenstrual age ] [ Designated as safety issue: Yes ]
    Chronic lung disease was defined as the need for oxygen at 36 weeks' postmenstrual age.


Secondary Outcome Measures:
  • Sepsis [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
    Sepsis was defined on the basis of a positive blood culture and treatment with antibiotics for at least five days (unless the infant died within five days).


Enrollment: 807
Study Start Date: January 1996
Study Completion Date: July 1999
Primary Completion Date: July 1997 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental
Vitamin A group.
Drug: Vitamin A
5,000 IU (0.1 ml) was given on Mondays, Wednesdays, and Fridays for four weeks.
Sham Comparator: Control
Sham procedure Control group.
Other: Sham Procedure
Control infants received a sham procedure rather than placebo injections.

Detailed Description:

Infants with extremely low birth weights (≤1,000 g) have low plasma and tissue concentrations of vitamin A, and vitamin A deficiency may predispose these infants to chronic lung disease. A meta-analysis of clinical trials of vitamin A supplementation for preterm infants revealed a 17% increase in the rate of survival without chronic lung disease, which approached statistical significance.

This multi-site, randomized trial was conducted to determine the safety and effectiveness of a higher dose of vitamin A than that used in previous trials in extremely-low-birth-weight (ELBW) infants. We hypothesized that vitamin A supplementation would increase the rate of survival without bronchopulmonary dysplasia and reduce the risk of sepsis.

Infants with birth weights from 401-1000g and who received mechanical ventilation or supplemental oxygen at 24-96 hours of age were enrolled. Subjects were randomized to either the vitamin A or a control group. Infants in the Vitamin A group were given a dose of 5000 IU (0.1 ml) intramuscularly on Mondays, Wednesdays, and Fridays for four weeks. Control infants received a sham procedure rather than placebo injections.

Serum vitamin A was measured in a central laboratory at base line and at 28 days in the first 300 infants. On study day 28 (two to three days after the last treatment and immediately after a blood sample was collected), the relative dose-response was evaluated.

  Eligibility

Ages Eligible for Study:   up to 96 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Infants wtih birth weights from 401-1,000g
  • Receiving mechanical ventilation or supplemental oxygen at 24-96 hours of age

Exclusion Criteria:

  • Major congenital anomalies
  • Congenital nonbacterial infection
  • Infants diagnosed with a terminal illness (as indicated by a pH below 6.80 or by the presence of hypoxia with bradycardia for more than two hours)
  • Infants who were to receive vitamin A in a parenteral fat emulsion or in doses exceeding recommendations for multivitamin preparations
  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: NCT01203488

Locations
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, District of Columbia
George Washington University
Washington, District of Columbia, United States, 20052
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Tennessee
University of Tennessee
Memphis, Tennessee, United States, 38163
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
Sponsors and Collaborators
Investigators
Study Director: Jon E. Tyson, MD MPH University of Texas Southwestern Medical Center
Principal Investigator: William Oh, MD Brown University, Women and Infants Hospital
Principal Investigator: Joel Verter, PhD George Washington University Biostatistics Center
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
Principal Investigator: Barbara J. Stoll, MD Emory University
Principal Investigator: James A. Lemons, MD Indiana University
Principal Investigator: David K. Stevenson, MD Stanford University
Study Director: Charles R. Bauer, MD University of Miami
Principal Investigator: Sheldon B. Korones, MD University of Tennessee
Principal Investigator: Edward F. Donovan, MD Case Western Reserve University
  More Information

Additional Information:
Publications:
Responsible Party: Jon E. Tyson, Lead Principal Investigator, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01203488     History of Changes
Other Study ID Numbers: NICHD-NRN-0015, U10HD021373, U10HD027904, U01HD019897, U10HD027871, M01RR006022, U10HD027851, U10HD027856, M01RR000750, U10HD027880, M01RR000070, U10HD021397, U10HD021415, U10HD021364, U10HD027853, M01RR008084, U10HD034216, U10HD021385, U10HD034167, U10HD027881, M01RR000997
Study First Received: September 15, 2010
Last Updated: January 9, 2011
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Prematurity
Vitamin A
Chronic Lung Disease

Additional relevant MeSH terms:
Birth Weight
Bronchopulmonary Dysplasia
Respiratory Distress Syndrome, Newborn
Sepsis
Body Weight
Signs and Symptoms
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Respiration Disorders
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
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 14, 2014