Hydrocortisone for BPD

Study ID
NICHD-NRN-0045

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)
  • Parkland Health & Hospital System

Contact
Diana Vasil
214/648-3789
diana.vasil@utsouthwestern.edu

Principal Investigator
Myra Wyckoff

Official Title

A Randomized Controlled Trial of the Effect Of Hydrocortisone on Survival Without Bronchopulmonary Dysplasia and on Neurodevelopmental Outcomes at 22 - 26 Months of Age in Intubated Infants < 30 Weeks Gestation Age

Brief Overview


The Hydrocortisone and Extubation study will test the safety and efficacy of a 10 day course
of hydrocortisone for infants who are less than 30 weeks estimated gestational age and who
are intubated at 14-28 days of life. Infants will be randomized to receive hydrocortisone
or placebo. This study will determine if hydrocortisone improves infants'survival without
moderate or severe BPD and will be associated with improvement in survival without moderate
or severe neurodevelopmental impairment at 22 - 26 months corrected age.

Summary


Bronchopulmonary dysplasia (BPD) remains a leading morbidity of the extremely preterm
infant, and prolonged mechanical ventilation is associated with increased risk for BPD.
Dexamethasone has been used previously to facilitate extubation and decrease the incidence
of BPD; however, due to adverse effects on neurodevelopmental outcomes, the use of this drug
has decreased. One cohort study suggests that hydrocortisone (HC) may facilitate
extubation. HC has thus far not been associated with adverse neurodevelopmental outcomes in
either cohort studies or randomized controlled trials. A recent meta-analysis of postnatal
corticosteroid therapy begun after the first week of life suggested that "late therapy may
reduce neonatal mortality without significantly increasing the risk of adverse long-term
neurodevelopmental outcomes," although the methodological quality of some of the follow-up
was acknowledged to be limited.

This is a randomized controlled trial to study the efficacy and safety of a 10-day tapering
course of hydrocortisone treatment for infants <30 weeks estimated gestational age at birth
who remain intubated at 14 - 28 days postnatal age. Based on previous Network data these
criteria define a population with a risk of death or BPD at 36 weeks postmenstrual age of
approximately 65 - 75%. The primary outcome for this study will incorporate both (1)
survival without moderate to severe BPD by Network physiologic definition and (2) survival
without moderate or severe NDI at 18 - 22 months corrected age. Therefore, the results of
this study will be reported only when follow-up data are available unless (1) the trial is
stopped early by the DSMC because of strong evidence of benefit or harm, or (2) at the time
all subjects have completed treatment the DCC finds a substantial survival benefit favoring
hydrocortisone (p<0.001). Individual study assignment will remain masked until the
follow-up is completed. Secondary outcomes will include short term measures such as
respiratory morbidities and growth at 36 weeks postmenstrual age and long term measures
including growth and other outcomes at 22 - 26 months corrected age.

Secondary studies include:

1)Effect of Hydrocortisone on the Cardiac mass of Premature Intubated Infants - will
determine left ventricular mass index at 36 weeks postmenstrual age (or prior to
discharge/transfer if after 34 weeks) in infants enrolled in the hydrocortisone for BPD RCT,
and compare HC-treated infants to placebo-treated infants. It will similarly assess and
compare the incidence of pulmonary hypertension in these patients. .

Participant Eligibility


Inclusion Criteria:

- infants <30 weeks estimated gestational age

- inborn at an NRN site or were admitted to an NRN site before 72 hours postnatal age

- have received at least 7days of mechanical ventilation;

- are receiving mechanical ventilation through an endotracheal tube .

Exclusion Criteria:

- Major congenital anomalies

- Decision to limit support

- Indomethacin or ibuprofen treatment within 48 hours of study drug

- Previous corticosteroid treatment for BPD

- Received hydrocortisone for 14 or more cumulative days

- Received hydrocortisone within 7 days of study entry