Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Randomized Trial of Hydrocortisone in Very Preterm Infants at High Risk for Neurologic and Pulmonary Impairments|
- Total Cerebral Volume as Measured by Volumetric Brain MRI [ Time Frame: 38 weeks postmenstrual age (PMA) ] [ Designated as safety issue: Yes ]Total cerebral volume included all brain gray matter and white matter, including cerebellum.
- Regional Brain Volumes [ Time Frame: 38-weeks postmenstrual age ] [ Designated as safety issue: Yes ]Cerebral white matter volume
- Duration of Positive Pressure Support (Mechanical Ventilation or Continuous Positive Airway Pressure) [ Time Frame: Up to 36 weeks PMA ] [ Designated as safety issue: No ]
- Duration of Oxygen Requirement [ Time Frame: Up to 36 weeks PMA ] [ Designated as safety issue: No ]
- Survival Without Severe Bronchopulmonary Dysplasia (BPD) [ Time Frame: 36 weeks postmenstrual age ] [ Designated as safety issue: No ]Using the NIH Consensus definition (Jobe A, 2001)
|Study Start Date:||November 2005|
|Study Completion Date:||November 2012|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
1. Tapering dose of hydrocortisone every 12 h over 7 day period
Hydrocortisone 3 mg/kg/d divided q 12h IV/PO tapered over 7 days
Placebo Comparator: 2
2. Identical-appearing saline placebo
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:
- Inclusion & Exclusion Criteria: See below.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00167544
|United States, Ohio|
|Nationwide Children's Hospital|
|Columbus, Ohio, United States, 432025|
|Principal Investigator:||Nehal A. Parikh, D.O., M.S.||The Research Institute at Nationwide Children's Hospital|