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

Phase 1

Completed

• Conditions: Infant, Low Birth Weight; Infant, Premature; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Sepsis; Infant, Newborn; Infant, Small for Gestational Age; Bronchopulmonary Dysplasia
• Interventions: Other: Sham Procedure; Drug: Vitamin A

• Registration Number: NCT01203488
• Lead Sponsor: NICHD Neonatal Research Network

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.

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 Timeline

• Study Start: 1996-01
• Primary Completion: 1997-07
• Study Completion: 1999-07
• Study First Submitted: 2010-09-15
• Study First Submitted QC: 2010-09-15
• Study First Posted: 2010-09-16
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-22
• Last Update Posted: 2017-09-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 807

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Sham Procedure	Sham procedure Control group.
Experimental	Vitamin A	Vitamin A group.

Primary Outcome Measures

Name	Time	Method
Chronic lung disease or death	36 weeks' postmenstrual age	Chronic lung disease was defined as the need for oxygen at 36 weeks' postmenstrual age.

Secondary Outcome Measures

Name	Time	Method
Sepsis	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).

Trial Locations

Locations (11)

Emory University; 🇺🇸 Atlanta, Georgia, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Case Western Reserve University, Rainbow Babies and Children's Hospital; 🇺🇸 Cleveland, Ohio, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Brown University, Women & Infants Hospital of Rhode Island; 🇺🇸 Providence, Rhode Island, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

George Washington University; 🇺🇸 Washington, D.C., District of Columbia, United States

Cincinnati Children's Medical Center; 🇺🇸 Cincinnati, Ohio, United States

University of Tennessee; 🇺🇸 Memphis, Tennessee, United States

University of Texas Southwestern Medical Center at Dallas; 🇺🇸 Dallas, Texas, United States