Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants

July 29, 2013 updated by: Nehal Parikh, Nationwide Children's Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

64

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 432025
        • Nationwide Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 week to 3 weeks (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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
Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
38 weeks postmenstrual age (PMA)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Regional Brain Volumes
Time Frame: 38-weeks postmenstrual age
Cerebral white matter volume
38-weeks postmenstrual age
Duration of Positive Pressure Support (Mechanical Ventilation or Continuous Positive Airway Pressure)
Time Frame: Up to 36 weeks PMA
Up to 36 weeks PMA
Duration of Oxygen Requirement
Time Frame: Up to 36 weeks PMA
Up to 36 weeks PMA
Survival Without Severe Bronchopulmonary Dysplasia (BPD)
Time Frame: 36 weeks postmenstrual age
Using the NIH Consensus definition (Jobe A, 2001)
36 weeks postmenstrual age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nationwide Children's Hospital

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health (NIH)

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

January 1, 2009

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 14, 2005

Study Record Updates

Last Update Posted (Estimate)

August 30, 2013

Last Update Submitted That Met QC Criteria

July 29, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • K23NS048152 (U.S. NIH Grant/Contract)
  • HSC-MS-05-0218

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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