We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00167544
Recruitment Status : Completed
First Posted : September 14, 2005
Results First Posted : August 30, 2013
Last Update Posted : August 30, 2013
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Nehal Parikh, Nationwide Children's Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Bronchopulmonary Dysplasia Encephalomalacia Premature Birth Drug: Hydrocortisone Drug: Placebo Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : November 2005
Actual Primary Completion Date : January 2009
Actual Study Completion Date : November 2012

Arm Intervention/treatment
Experimental: 1
1. Tapering dose of hydrocortisone every 12 h over 7 day period
Drug: Hydrocortisone
Hydrocortisone 3 mg/kg/d divided q 12h IV/PO tapered over 7 days

Placebo Comparator: 2
2. Identical-appearing saline placebo
Drug: Placebo

Primary Outcome Measures :
  1. Total Cerebral Volume as Measured by Volumetric Brain MRI [ Time Frame: 38 weeks postmenstrual age (PMA) ]
    Total cerebral volume included all brain gray matter and white matter, including cerebellum.

Secondary Outcome Measures :
  1. Regional Brain Volumes [ Time Frame: 38-weeks postmenstrual age ]
    Cerebral white matter volume

  2. Duration of Positive Pressure Support (Mechanical Ventilation or Continuous Positive Airway Pressure) [ Time Frame: Up to 36 weeks PMA ]
  3. Duration of Oxygen Requirement [ Time Frame: Up to 36 weeks PMA ]
  4. Survival Without Severe Bronchopulmonary Dysplasia (BPD) [ Time Frame: 36 weeks postmenstrual age ]
    Using the NIH Consensus definition (Jobe A, 2001)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   1 Week to 3 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00167544

Layout table for location information
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 432025
Sponsors and Collaborators
Nationwide Children's Hospital
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Layout table for investigator information
Principal Investigator: Nehal A. Parikh, D.O., M.S. The Research Institute at Nationwide Children's Hospital
Additional Information:
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Nehal Parikh, Associate Professor of Pediatrics, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT00167544    
Other Study ID Numbers: K23NS048152 ( U.S. NIH Grant/Contract )
K23NS048152 ( U.S. NIH Grant/Contract )
First Posted: September 14, 2005    Key Record Dates
Results First Posted: August 30, 2013
Last Update Posted: August 30, 2013
Last Verified: July 2013
Keywords provided by Nehal Parikh, Nationwide Children's Hospital:
Bronchopulmonary Dysplasia
Brain injury
Neurosensory impairment
Anti-Inflammatory Agents
Extremely Low Birth Weight (ELBW) infants
Premature Birth
Magnetic Resonance Imaging
Additional relevant MeSH terms:
Layout table for MeSH terms
Bronchopulmonary Dysplasia
Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anti-Inflammatory Agents