The purpose of this study is to determine whether treatment of very preterm infants at high-risk for lung and brain injury with hydrocortisone results in improved pulmonary and neurologic outcomes.

Condition	Intervention	Phase
Bronchopulmonary Dysplasia Encephalomalacia Premature Birth	Drug: Hydrocortisone	Phase II

Further Study Details: 

Primary Outcomes: Total cerebral volume as measured by volumetric brain MRI at 38 weeks post-menstrual age.
Secondary Outcomes: Neurosensory impairments at 18 to 22 months adjusted age; Regional brain volumes; Duration of mechanical ventilation; Duration of oxygen requirement; Diagnosis of BPD
Expected Total Enrollment:  56

Hypothesis: Among extremely low birth weight infants (ELBW; BW ≤ 1000g) 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 increase 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 Criteria: All ELBW infants admitted to Memorial Hermann Children''''s Hospital (MHCH) who are ventilator-dependent between 14 and 21 days of age with a predefined respiratory index score.
2. Exclusion Criteria: Infants with 1) prior postnatal steroid treatment, 2) evidence of sepsis or necrotizing enterocolitis, 3) known major congenital anomalies of the cardiopulmonary or central nervous system or 4) infants being treated with indomethacin or those likely to require treatment in the next 7 days as judged by the treating physician.
3. 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 brain MRI (routinely done on all ELBW infants at 38 weeks post-menstrual age) will also be accessed by the study investigators to perform volumetric analysis and determine the total and component volume of brain regions. Administration of indomethacin or dexamethasone to enrolled infants will be closely monitored and regulated throughout the trial period. 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.

Ages Eligible for Study:  up to  3 Weeks,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Patient in the Memorial Hermann Children’s Hospital (MHCH) NICU with a birth weight ≤ 1000 grams.
• Ventilator-dependent between 14 and 21 days of age.
• Respiratory index score (RIS: mean airway pressure x fraction of inspired oxy-gen) 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 (judged by the treating physician)
• 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.

Please refer to this study by ClinicalTrials.gov identifier  NCT00167544

Georgia E. McDavid, RN      713-500-5734    Georgia.E.Mcdavid@uth.tmc.edu
Nehal A. Parikh, D.O.      713-500-6470    Nehal.A.Parikh@uth.tmc.edu

Texas
      Memorial Hermann Children''''s Hospital, Houston,  Texas,  77030,  United States

Study chairs or principal investigators

Nehal A. Parikh, D.O.,  Principal Investigator,  University of Texas Health Science Center Medical School at Houston   

Study ID Numbers:  K23NS048152-2; 1 K23NS 048152-01A1; HSC-MS-05-0218
Last Updated:  September 13, 2005
Record first received:  September 9, 2005
ClinicalTrials.gov Identifier:  NCT00167544
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-09-20