Vitamin E for Extremely Preterm Infants

Infant, Premature Clinical Trial

Official title:

Single-Dose Vitamin E for Prevention of Mortality and Morbidity in Extremely Preterm Infants: Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01193270
• Other study ID #: NICHD-NRN-0044
• Secondary ID: U10HD021364U10HD
• Status: Completed
• Phase: Phase 1
• First received: August 31, 2010
• Last updated: November 10, 2015
• Start date: October 2010
• Est. completion date: August 2011

Study information

• Verified date: November 2015
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this pilot trial is to test the safety and efficacy of administering one dose of vitamin E, via a tube into the stomach, to extremely preterm infants (less than 27 weeks gestation and less than 1000 grams birth weight). This pilot will examine whether a single dose of vitamin E will be absorbed into the infants' bloodstreams with resulting serum α-tocopherol level in the target range of 1-3 mg/dl.

Description:

Intraventricular hemorrhage (IVH) -- bleeding into the brain's ventricular system -- is one of the most common complications of prematurity, affecting an estimated 10-40% of very low birth weight (<1500 g) infants born at less than 35 weeks of gestation. Mortality from severe (high-grade) IVH is 27-50%. Severe IVH can result in developmental delays and life-long neurological deficits, including cerebral palsy and seizures.

A number of strategies have been used in efforts to prevent IVH, including: antenatal corticosteroids, maternal vitamin K, delayed clamping of the umbilical cord, indomethacin, ethamsylate, inositol, and muscle paralysis. With the exception of antenatal corticosteroids and indomethacin, these measures have met with only limited success. Supplemental vitamin E, given in the first few hours of life to all premature infants, offers a promising low-risk approach to preventing and/or lessening the severity of IVH.

This safety and efficacy pilot trial will examine whether one dose of vitamin E (dl-α-tocopheryl acetate), given intragastrically to preterm infants <27 weeks gestation and <1000 grams birth weight, will produce blood serum α-tocopherol levels in the target range of 1-3 mg/dl. Based on the results of this pilot, a Phase III randomized control trial will be developed to test whether a single dose of vitamin E can reduce the incidence of death or neurodevelopmental impairment at 18-22 months corrected age in these preterm infants.

Most intraventricular hemorrhages occur in the first 72 hours after birth. Because of this, to prevent IVH, it must be given as soon as possible after birth. Eligible, consented infants will be assigned to either a vitamin E group or a placebo group. Infants in the vitamin E group will receive 1.0 ml/kg of dl-α-tocopheryl acetate (Aquasol E®); infants in the placebo control group will receive a similar amount of sterile water. The dose will be given within 4 hours of birth via a tube into the stomach. Blood samples will be taken from all infants before the dose is given, 24 hours after dosing, and 7 days after dosing to measure how well the vitamin E is absorbed into the bloodstream.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 4 Hours

Eligibility

Inclusion Criteria:

• Less than 27 completed weeks gestational age

• Birth weight less than 1,000 grams

• Inborn infants

Exclusion Criteria:

• Infant's treatment will be limited based on poor prognosis

• Umbilical cord or blood pH below 7.0

• Antenatally diagnosed brain abnormality, including hemorrhage

• Major congenital malformations, including those for which feeding is contraindicated

• Mother of infant enrolled in a clinical trial of vitamin E supplementation

• Mother of infant reports self administration of monovitamin supplements of vitamin E during pregnancy or labor

• Infant has received supplemental vitamin E (except multivitamin additive in parenteral nutrition or through enteral milk or formula feeds)

• Greater than four hours of age

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Birth Weight
• Hemorrhage
• Infant, Newborn
• Infant, Premature
• Infant, Small for Gestational Age
• Infant, Very Low Birth Weight
• Intracranial Hemorrhages

Intervention

Drug:
• Vitamin E
A single intragastric dose of dl-a-tocopheryl acetate 50 IU/kg.
• Placebo
Sterile water in volume equal to that of the comparator drug

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
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	Wayne State University	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
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	University of Utah	Salt Lake City	Utah

Sponsors (3)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Bell EF, Hansen NI, Brion LP, Ehrenkranz RA, Kennedy KA, Walsh MC, Shankaran S, Acarregui MJ, Johnson KJ, Hale EC, Messina LA, Crawford MM, Laptook AR, Goldberg RN, Van Meurs KP, Carlo WA, Poindexter BB, Faix RG, Carlton DP, Watterberg KL, Ellsbury DL, Da — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum tocopherol levels	Blood samples will be tested for tocopherol levels at baseline, 24 hours, and 7 days.	Birth to 7 days	No

External Links

•   Neonatal Research Network website