Vitamin E for Extremely Preterm Infants

Study Overview
=================
Brief 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.

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.

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

Conditions
-----------------
Infant, Newborn, Infant, Small for Gestational Age, Infant, Very Low Birth Weight, Infant, Premature, Intracranial Hemorrhages

Intervention / Treatment
-----------------
* Drug: Vitamin E
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Maximum Age: 4 Hours

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NICHD Neonatal Research Network, Intraventricular Hemorrhage (IVH), Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity