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

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ClinicalTrials.gov Identifier: NCT01203488

Recruitment Status : Completed

First Posted : September 16, 2010

Last Update Posted : September 26, 2017

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Sponsor:

Collaborator:

National Center for Research Resources (NCRR)

Information provided by:

NICHD Neonatal Research Network

Study Description

Brief Summary:

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 or disease	Intervention/treatment	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

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	807 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	Randomized Trial of Vitamin A Supplementation for Extremely-Low-Birth-Weight
Study Start Date :	January 1996
Actual Primary Completion Date :	July 1997
Actual Study Completion Date :	July 1999

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Birth Weight Body Weight Vitamin A

Drug Information available for: Retinol Vitamin A palmitate Vitamin A

Genetic and Rare Diseases Information Center resources: Respiratory Distress Syndrome, Infant Acute Respiratory Distress Syndrome Bronchopulmonary Dysplasia Chronic Graft Versus Host Disease

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

Chronic lung disease or death [ Time Frame: 36 weeks' postmenstrual age ]
Chronic lung disease was defined as the need for oxygen at 36 weeks' postmenstrual age.

Secondary Outcome Measures :

Sepsis [ Time Frame: 5 days ]
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).

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	24 Hours to 96 Hours (Child)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01203488

Locations

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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, D.C., 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

NICHD Neonatal Research Network

National Center for Research Resources (NCRR)

Investigators

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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:

NICHD Neonatal Research Network This link exits the ClinicalTrials.gov site

Publications of Results:

Kennedy KA, Stoll BJ, Ehrenkranz RA, Oh W, Wright LL, Stevenson DK, Lemons JA, Sowell A, Mele L, Tyson JE, Verter J. Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low? The NICHD Neonatal Research Network. Early Hum Dev. 1997 Jul 24;49(1):19-31. doi: 10.1016/s0378-3782(97)01869-0.

Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA, Stoll BJ, Lemons JA, Stevenson DK, Bauer CR, Korones SB, Fanaroff AA. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 1999 Jun 24;340(25):1962-8. doi: 10.1056/NEJM199906243402505.

Ambalavanan N, Tyson JE, Kennedy KA, Hansen NI, Vohr BR, Wright LL, Carlo WA; National Institute of Child Health and Human Development Neonatal Research Network. Vitamin A supplementation for extremely low birth weight infants: outcome at 18 to 22 months. Pediatrics. 2005 Mar;115(3):e249-54. doi: 10.1542/peds.2004-1812. Epub 2005 Feb 15.

Other Publications:

Stark AR, Tyson JE, Hibberd PL. Variation among institutional review boards in evaluating the design of a multicenter randomized trial. J Perinatol. 2010 Mar;30(3):163-9. doi: 10.1038/jp.2009.157. Epub 2009 Oct 1.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rysavy MA, Li L, Tyson JE, Jensen EA, Das A, Ambalavanan N, Laughon MM, Greenberg RG, Patel RM, Pedroza C, Bell EF; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Should Vitamin A Injections to Prevent Bronchopulmonary Dysplasia or Death Be Reserved for High-Risk Infants? Reanalysis of the National Institute of Child Health and Human Development Neonatal Research Network Randomized Trial. J Pediatr. 2021 Sep;236:78-85.e5. doi: 10.1016/j.jpeds.2021.05.022. Epub 2021 May 15.

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Responsible Party:	Jon E. Tyson, Lead Principal Investigator, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT01203488
Other Study ID Numbers:	NICHD-NRN-0015 U10HD021373 ( U.S. NIH Grant/Contract ) U10HD027904 ( U.S. NIH Grant/Contract ) U01HD019897 ( U.S. NIH Grant/Contract ) U10HD027871 ( U.S. NIH Grant/Contract ) M01RR006022 ( U.S. NIH Grant/Contract ) U10HD027851 ( U.S. NIH Grant/Contract ) U10HD027856 ( U.S. NIH Grant/Contract ) M01RR000750 ( U.S. NIH Grant/Contract ) U10HD027880 ( U.S. NIH Grant/Contract ) M01RR000070 ( U.S. NIH Grant/Contract ) U10HD021397 ( U.S. NIH Grant/Contract ) U10HD021415 ( U.S. NIH Grant/Contract ) U10HD021364 ( U.S. NIH Grant/Contract ) U10HD027853 ( U.S. NIH Grant/Contract ) M01RR008084 ( U.S. NIH Grant/Contract ) U10HD034216 ( U.S. NIH Grant/Contract ) U10HD021385 ( U.S. NIH Grant/Contract ) U10HD034167 ( U.S. NIH Grant/Contract ) U10HD027881 ( U.S. NIH Grant/Contract ) M01RR000997 ( U.S. NIH Grant/Contract )
First Posted:	September 16, 2010 Key Record Dates
Last Update Posted:	September 26, 2017
Last Verified:	September 2017

Keywords provided by NICHD Neonatal Research Network:


NICHD Neonatal Research Network Extremely Low Birth Weight (ELBW) Prematurity Vitamin A Chronic Lung Disease

Additional relevant MeSH terms:

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Respiratory Distress Syndrome Respiratory Distress Syndrome, Newborn Bronchopulmonary Dysplasia Body Weight Birth Weight Lung Diseases Respiratory Tract Diseases Respiration Disorders	Infant, Premature, Diseases Infant, Newborn, Diseases Ventilator-Induced Lung Injury Lung Injury Vitamin A Vitamins Micronutrients Physiological Effects of Drugs

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