Hydrocortisone for BPD

Brief Title

Hydrocortisone for BPD

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 Summary

      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.
    

Detailed Description

      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.

        2. Extended follow-up: Subjects will be seen for a follow-up visit at 5-6 years corrected
           age to assess functional developmental and respiratory outcomes at early school age. In
           a subset of five Neonatal Research Network Clinical Centers, impulse oscillometry (IOS),
           which is the optimal direct measure of lung capacity and function, will be performed to
           validate the 6-minute walk test and International Study of Asthma and Allergies in
           Childhood (ISAAC) questionnaire as functional measures of pulmonary status. Also at
           these five Centers, the six minute walk test, ISAAAC questionnaire, and IOS will be
           administered as part of (1) the Healthy Lungs sub-study, which will recruit 120 TOP 5
           study participants who had minimal lung disease when they were infants to define
           normative ranges in healthy, preterm-born children, and (2) the Healthy Lungs Two
           sub-study, which will recruit 120 healthy, term-born children without history of lung
           disease to characterize functional and mechanical respiratory outcomes at 5-7 years of
           age.
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Survival Without Moderate/Severe Physiologic Bronchopulmonary Dysplasia (BPD)

Secondary Outcome

 Number of Participants With Successful Extubation

Condition

Infant, Newborn

Intervention

Hydrocortisone

Study Arms / Comparison Groups

 Placebo

Description:  Saline placebo

Publications

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

Recruitment Status

Drug

Estimated Enrollment

800

Start Date

August 11, 2011

Completion Date

January 2025

Primary Completion Date

September 21, 2020

Eligibility Criteria

        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
      

Gender

All

Ages

N/A - 30 Weeks

Accepts Healthy Volunteers

No

Contacts

Michele C Walsh, MD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT01353313

Organization ID

NICHD-NRN-0045

Secondary IDs

U10HD034216

Responsible Party

Sponsor

Study Sponsor

NICHD Neonatal Research Network

Collaborators

 National Center for Research Resources (NCRR)

Study Sponsor

Michele C Walsh, MD, Principal Investigator, Case Western Reserve University, Rainbow Babies and Children's Hospital

Verification Date

July 2022