Hydrocortisone for BPD

Last updated on July 2021

Recruitment

Recruitment Status: Active, not recruiting
Estimated Enrollment: Same as current

Summary

Conditions

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

Type

Interventional

Phase

Phase 3

Design

Allocation: RandomizedIntervention Model: Parallel AssignmentMasking: Triple (Participant, Care Provider, Investigator)Primary Purpose: Prevention

Participation Requirements

Age: Younger than 30 years
Gender: Both males and females

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. 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.

Tracking Information

NCT #

NCT01353313

Collaborators

National Center for Research Resources (NCRR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator: Michele C Walsh, MD Case Western Reserve University, Rainbow Babies and Children's Hospital Principal Investigator: Seetha Shankaran, MD Wayne State University Principal Investigator: Abbot R Laptook, MD Brown University, Women & Infants Hospital of Rhode Island Principal Investigator: C. Michael Cotten, MD Duke University Principal Investigator: David Carlton, MD Emory University Principal Investigator: Greg Sokol, MD Indiana University Principal Investigator: Abhik Das, PhD RTI International Principal Investigator: Krisa P Van Meurs, MD Stanford University Principal Investigator: Brenda P Poindexter, MD Children's Hospital Medical Center, Cincinnati Principal Investigator: Waldemar A Carlo, MD University of Alabama at Birmingham Principal Investigator: Edward F Bell, MD University of Iowa Study Chair: Kristi L Watterberg, MD University of New Mexico Principal Investigator: Myra Wyckoff, MD University of Texas, Southwestern Medical Center at Dallas Principal Investigator: Jon E Tyson, MD, MPH The University of Texas Health Science Center, Houston Principal Investigator: Eric Eichenwald, MD University of Pennsylvania Principal Investigator: Carl T D'Angio, MD University of Rochester Principal Investigator: Uday Devaskar, MD University of California, Los Angeles Principal Investigator: Pablo J Sanchez, MD Research Institute at Nationwide Children's Hospital Principal Investigator: William Truog, MD Children's Mercy Hospital Kansas City Principal Investigator: Bradley Yoder, MD University of Utah