Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants
Information source: Nationwide Children's Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bronchopulmonary Dysplasia; Encephalomalacia; Premature Birth
Intervention: Hydrocortisone (Drug); Placebo (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Nationwide Children's Hospital Official(s) and/or principal investigator(s): Nehal A. Parikh, D.O., M.S., Principal Investigator, Affiliation: The Research Institute at Nationwide Children's Hospital
Summary
The purpose of this study is to determine whether treatment of very preterm infants at
high-risk for lung and brain injury with low dose hydrocortisone results in improved
pulmonary and neurologic outcomes.
Clinical Details
Official title: A Randomized Trial of Hydrocortisone in Very Preterm Infants at High Risk for Neurologic and Pulmonary Impairments
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: Total Cerebral Volume as Measured by Volumetric Brain MRI
Secondary outcome: Regional Brain VolumesDuration of Positive Pressure Support (Mechanical Ventilation or Continuous Positive Airway Pressure) Duration of Oxygen Requirement Survival Without Severe Bronchopulmonary Dysplasia (BPD)
Detailed description:
Hypothesis: Among extremely low birth weight infants (ELBW; BW ≤ 1000 g) at high risk for
bronchopulmonary dysplasia (BPD) and neurologic impairments, those infants randomized to
seven days of hydrocortisone will demonstrate increased total cerebral tissue volumes as
compared to infants randomized to placebo.
Specific Aims: 1) To perform a pilot blinded randomized controlled trial of a 7-day regimen
of low dose hydrocortisone in ELBW infants at high risk for BPD and neurosensory impairments
and assess its effect on cerebral tissue volumes. 2) Evaluate and report 2 year
neurodevelopmental outcomes.
Background and Significance: Bronchopulmonary dysplasia is a disease of arrested lung
development and lung inflammation. It is primarily seen in ELBW infants. Neurological
delay, including cerebral palsy and mental retardation, affect up to 40%-50% of surviving
ELBW infants. BPD is an important risk factor for such neurological delay. Postnatal
administration of corticosteroids to ventilated preterm neonates results in a reduced risk
of developing BPD. Postnatal corticosteroids however have shown harmful effects on the
brain and can lead to increased rates of cerebral palsy and learning problems. This effect
has primarily been seen with dexamethasone when high doses were given in the first week of
life. Beyond the first week of life, there is insufficient information on the effects of
steroids on the brain. Steroids other than dexamethasone, in much lower doses have been
shown to improve short term lung function with minimal short-term side effects. A review
study of all steroid trials for BPD shows that when given to a high risk group of infants (>
50% risk of BPD) steroids protect the brain and reduce rates of cerebral palsy. The
American and Canadian Pediatric societies and respected researchers have commented on the
urgent need for more trials of other corticosteroids at lower doses started after the first
week of life to evaluate their short and long-term pulmonary and neurological benefits and
risks.
Research Design and Methods:
1. Inclusion & Exclusion Criteria: See below.
2. Procedures: Consented eligible patients will be randomly assigned to receive
hydrocortisone in a tapering schedule over 7 days or placebo (comparison group). Study
drug will be given every 12 hours IV with only study pharmacist aware of assignment.
The patient's anatomic brain MRI (routinely done on all ELBW infants at 38 weeks
post-menstrual age) will be further processed by the masked study investigators to
derive total and regional brain volumes. Administration of indomethacin or
dexamethasone to enrolled infants will be closely monitored and regulated throughout
the trial period. Indomethacin use during study period is contraindicated.
Dexamethasone (or other steroid) use will be restricted to ELBW infants on high
ventilator settings (RIS > 10) after 28 days of life. All other procedures will be per
routine care. Blinded developmental follow-up at two years, already currently
performed for all ELBW infants at MHCH, will be analyzed and reported for all study
infants.
Eligibility
Minimum age: N/A.
Maximum age: 3 Weeks.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patient in the Memorial Hermann Children's Hospital (MHCH) neonatal intensive care
unit with a birth weight ≤ 1000 grams.
- Ventilator-dependent between 10 and 21 days of age.
- Respiratory index score (RIS: mean airway pressure x fraction of inspired oxygen) of
≥ 2. 0 that is increasing or stable for the previous 24 hours or a RIS ≥ 3. 0 if
improvement noted in the past 24 hours.
Exclusion Criteria:
- Prior postnatal steroid treatment.
- Evidence of sepsis or necrotizing enterocolitis.
- Known major congenital anomalies of the cardiopulmonary or central nervous system.
- Infants being treated with indomethacin or those likely to require treatment in the
next 7 days as judged by the treating physician.
- Inability or unwillingness of parent or legal guardian/representative to give written
informed consent.
- Gestational age < 23 weeks.
Locations and Contacts
Nationwide Children's Hospital, Columbus, Ohio 432025, United States
Additional Information
Patient information page - Bronchopulmonary Dysplasia
Related publications: Parikh NA, Lasky RE, Kennedy KA, Moya FR, Hochhauser L, Romo S, Tyson JE. Postnatal dexamethasone therapy and cerebral tissue volumes in extremely low birth weight infants. Pediatrics. 2007 Feb;119(2):265-72. Yu X, Zhang Y, Lasky RE, Datta S, Parikh NA, Narayana PA. Comprehensive brain MRI segmentation in high risk preterm newborns. PLoS One. 2010 Nov 8;5(11):e13874. doi: 10.1371/journal.pone.0013874.
Starting date: November 2005
Last updated: July 29, 2013
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