Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants

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Brief Title

Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants

Official Title

A Randomized Trial of Hydrocortisone in Very Preterm Infants at High Risk for Neurologic and Pulmonary Impairments

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.
    

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Total Cerebral Volume as Measured by Volumetric Brain MRI

Secondary Outcome

 Regional Brain Volumes

Condition

Bronchopulmonary Dysplasia

Intervention

Hydrocortisone

Study Arms / Comparison Groups

 1
Description:  1. Tapering dose of hydrocortisone every 12 h over 7 day period

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

64

Start Date

November 2005

Completion Date

November 2012

Primary Completion Date

January 2009

Eligibility 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.
      

Gender

All

Ages

N/A - 3 Weeks

Accepts Healthy Volunteers

No

Contacts

Nehal A. Parikh, D.O., M.S., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00167544

Organization ID

K23NS048152

Secondary IDs

K23NS048152

Responsible Party

Principal Investigator

Study Sponsor

Nationwide Children's Hospital

Collaborators

 National Institutes of Health (NIH)

Study Sponsor

Nehal A. Parikh, D.O., M.S., Principal Investigator, The Research Institute at Nationwide Children's Hospital


Verification Date

July 2013