Vitamin E for Extremely Preterm Infants

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

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.

Study Overview

• Status: Completed
• Conditions: Intracranial Hemorrhages; Infant, Very Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature; Infant, Newborn
• Intervention / Treatment: Drug: Vitamin E; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Connecticut
    • New Haven, Connecticut, United States, 06504
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Durham, North Carolina, United States, 27705
      • RTI International
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University, Rainbow Babies and Children's Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Brown University, Women & Infants Hospital of Rhode Island
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 4 hours (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin E; A single intragastric dose of dl-α-tocopheryl acetate (Aquasol E®) 50 IU/kg.	Drug: Vitamin E; A single intragastric dose of dl-α-tocopheryl acetate 50 IU/kg.; Other Names: Aquasol E®
Placebo Comparator: Placebo; Sterile water in volume equal to that of the comparator drug.	Drug: Placebo; Sterile water in volume equal to that of the comparator drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum tocopherol levels	Blood samples will be tested for tocopherol levels at baseline, 24 hours, and 7 days.	Birth to 7 days

Collaborators and Investigators

• Sponsor: NICHD Neonatal Research Network
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Ivan D. Frantz, III, MD, Tufts Medical Center; Study Chair: Edward F. Bell, MD, University of Iowa

Publications and helpful links

General Publications

• 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, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth. Pediatrics. 2013 Dec;132(6):e1626-33. doi: 10.1542/peds.2013-1684. Epub 2013 Nov 11.

Helpful Links

• Neonatal Research Network website

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: August 31, 2010
• First Submitted That Met QC Criteria: August 31, 2010
• First Posted (Estimate): September 1, 2010

Study Record Updates

• Last Update Posted (Estimate): November 11, 2015
• Last Update Submitted That Met QC Criteria: November 10, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Prematurity; NICHD Neonatal Research Network; Very Low Birth Weight (VLBW); Extremely Low Birth Weight (ELBW); Intraventricular Hemorrhage (IVH)
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Body Weight; Hemorrhage; Birth Weight; Intracranial Hemorrhages; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E
• Other Study ID Numbers: NICHD-NRN-0044; U10HD036790 (U.S. NIH Grant/Contract); U10HD021364 (U.S. NIH Grant/Contract); U10HD021373 (U.S. NIH Grant/Contract); U10HD021385 (U.S. NIH Grant/Contract); U10HD027851 (U.S. NIH Grant/Contract); U10HD027856 (U.S. NIH Grant/Contract); U10HD027871 (U.S. NIH Grant/Contract); U10HD027880 (U.S. NIH Grant/Contract); U10HD027904 (U.S. NIH Grant/Contract); U10HD034216 (U.S. NIH Grant/Contract); U10HD040492 (U.S. NIH Grant/Contract); U10HD040689 (U.S. NIH Grant/Contract); U10HD053089 (U.S. NIH Grant/Contract); U10HD053109 (U.S. NIH Grant/Contract); U10HD053119 (U.S. NIH Grant/Contract); U10HD053124 (U.S. NIH Grant/Contract); UL1RR024139 (U.S. NIH Grant/Contract); UL1RR025744 (U.S. NIH Grant/Contract); UL1RR024979 (U.S. NIH Grant/Contract); UL1RR025764 (U.S. NIH Grant/Contract); UL1RR025008 (U.S. NIH Grant/Contract); UL1RR025761 (U.S. NIH Grant/Contract)