Hydrocortisone for BPD

• Efficacy [ Time Frame: Birth to 26 months corrected age ] [ Designated as safety issue: Yes ]
  Improvement in survival without physiologically defined moderate to severe BPD.
• Safety [ Time Frame: Birth to 26 months corrected age ] [ Designated as safety issue: Yes ]
  Survival without moderate or severe neurodevelopmental impairment at 18 - 22 months corrected age

• Efficacy [ Time Frame: Birth to 22 months corrected age ] [ Designated as safety issue: Yes ]
  Improvement in survival without physiologically defined moderate to severe BPD.
• Safety [ Time Frame: Birth to 22 months corrected age ] [ Designated as safety issue: Yes ]
  Survival without moderate or severe neurodevelopmental impairment at 18 - 22 months corrected age

• Morbidity and Growth [ Time Frame: Birth to 26 months corrected age ] [ Designated as safety issue: Yes ]
• Successful Extubation [ Time Frame: 36 Weeks Post Menstrual Age ] [ Designated as safety issue: Yes ]
• Use of open-label dexamethasone [ Time Frame: 36 Weeks Post Menstrual Age ] [ Designated as safety issue: Yes ]
• Respiratory status at 40 weeks [ Time Frame: 40 weeks Postmenstrual Age ] [ Designated as safety issue: Yes ]

• Morbidity and Growth [ Time Frame: Birth to 22 months corrected age ] [ Designated as safety issue: Yes ]
• Successful Extubation [ Time Frame: 36 Weeks Post Menstrual Age ] [ Designated as safety issue: Yes ]
• Use of open-label dexamethasone [ Time Frame: 36 Weeks Post Menstrual Age ] [ Designated as safety issue: Yes ]
• Respiratory status at 40 weeks [ Time Frame: 40 weeks Postmenstrual Age ] [ Designated as safety issue: Yes ]

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.

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.

• Infant, Newborn
• Infant, Small for Gestational Age
• Infant, Very Low Birth Weight
• Infant, Premature
• Bronchopulmonary Dysplasia

• Drug: Hydrocortisone

  Hydrocortisone sodium succinate for intravenous administration (unpreserved, Solu-Cortef plain, Pfizer®, reconstituted with unpreserved normal saline to avoid exposure to the benzyl alcohol contained in preserved diluents), to be administered either intravenously or orally if no intravenous line is available at the same dose, and tapered as follows:

  4mg/kg/day ¸ q 6 hours x 2 days, then 2mg/kg/day ¸ q 6 hours x 3 days; then

  1mg/kg/day ¸ q 12 hours x 3 days; then 0.5mg/kg/d as a single dose x 2 days

• Drug: Placebo

  Saline placebo to be administered either intravenously or orally if no intravenous line is available, at the same dose, and tapered as follows:

  4mg/kg/day ¸ q 6 hours x 2 days, then 2mg/kg/day ¸ q 6 hours x 3 days; then

  1mg/kg/day ¸ q 12 hours x 3 days; then 0.5mg/kg/d as a single dose x 2 days

• Placebo Comparator: Placebo
  Saline placebo
  Intervention: Drug: Placebo
• Experimental: Hydrocortisone
  hydrocortisone sodium succinate for intravenous administration (unpreserved, Solu-Cortef plain, Pfizer®, reconstituted with unpreserved normal saline to avoid exposure to the benzyl alcohol contained in preserved diluents)
  Intervention: Drug: Hydrocortisone

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