Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Nehal Parikh, Nationwide Children's Hospital
ClinicalTrials.gov Identifier:
NCT00167544
First received: September 9, 2005
Last updated: July 29, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Bronchopulmonary Dysplasia
Encephalomalacia
Premature Birth
Drug: Hydrocortisone
Drug: Placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Nationwide Children's Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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)


Enrollment: 64
Study Start Date: November 2005
Study Completion Date: November 2012
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   up to 3 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00167544

Locations
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 432025
Sponsors and Collaborators
Nationwide Children's Hospital
Investigators
Principal Investigator: Nehal A. Parikh, D.O., M.S. The Research Institute at Nationwide Children's Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Nehal Parikh, Associate Professor of Pediatrics, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT00167544     History of Changes
Other Study ID Numbers: K23NS048152, K23NS048152, HSC-MS-05-0218
Study First Received: September 9, 2005
Results First Received: March 25, 2013
Last Updated: July 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Nationwide Children's Hospital:
Bronchopulmonary Dysplasia
Encephalomalacia
Brain injury
Neurosensory impairment
Corticosteroids
Anti-Inflammatory Agents
Extremely Low Birth Weight (ELBW) infants
Premature Birth
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Bronchopulmonary Dysplasia
Encephalomalacia
Premature Birth
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
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Anti-Inflammatory Agents
Hydrocortisone
Hydrocortisone-17-butyrate
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on August 26, 2014