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

Sepsis Clinical Trial

— Vitamin A  

Official title:

Randomized Trial of Vitamin A Supplementation for Extremely-Low-Birth-Weight

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01203488
• Other study ID #: NICHD-NRN-0015
• Secondary ID: U10HD021373U10HD
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 15, 2010
• Last updated: September 22, 2017
• Start date: January 1996
• Est. completion date: July 1999

Study information

• Verified date: September 2017
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 807
• Est. completion date: July 1999
• Est. primary completion date: July 1997
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 96 Hours

Eligibility

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

Related Conditions & MeSH terms

• Birth Weight
• Body Weight
• Bronchopulmonary Dysplasia
• Infant, Low Birth Weight
• Infant, Newborn
• Infant, Premature
• Infant, Small for Gestational Age
• Respiration, Artificial
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Sepsis

Intervention

Drug:
• Vitamin A
5,000 IU (0.1 ml) was given on Mondays, Wednesdays, and Fridays for four weeks.

Other:
• Sham Procedure
Control infants received a sham procedure rather than placebo injections.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Tennessee	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	George Washington University	Washington, D.C.	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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 N — View Citation

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. — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chronic lung disease or death	Chronic lung disease was defined as the need for oxygen at 36 weeks' postmenstrual age.	36 weeks' postmenstrual age
Secondary	Sepsis	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).	5 days

External Links

•   NICHD Neonatal Research Network