Hydrocortisone for BPD

Condition(s) targeted: Infant, Newborn; Infant, Small for Gestational Age; Infant, Very Low Birth Weight; Infant, Premature; Bronchopulmonary Dysplasia

Intervention: Hydrocortisone (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: NICHD Neonatal Research Network

Official(s) and/or principal investigator(s):
Michele C Walsh, MD, Principal Investigator, Affiliation: Case Western Reserve University, Rainbow Babies and Children's Hospital
Seetha Shankaran, MD, Principal Investigator, Affiliation: Wayne State University
Abbot R Laptook, MD, Principal Investigator, Affiliation: Brown University, Women & Infants Hospital of Rhode Island
Ron N Goldberg, MD, Principal Investigator, Affiliation: Duke University
Barbara J Stoll, MD, Principal Investigator, Affiliation: Emory University
Brenda B Poindexter, MD, MS, Principal Investigator, Affiliation: Indiana University
Abhik Das, PhD, Principal Investigator, Affiliation: RTI International
Krisa P Van Meurs, MD, Principal Investigator, Affiliation: Stanford University
Kurt Schibler, MD, Principal Investigator, Affiliation: Cincinnati Children's Medical Center
Waldemar A Carlo, MD, Principal Investigator, Affiliation: University of Alabama at Birmingham
Edward F Bell, MD, Principal Investigator, Affiliation: University of Iowa
Kristi L Watterberg, MD, Study Chair, Affiliation: University of New Mexico
Pablo J Sanchez, MD, Principal Investigator, Affiliation: University of Texas Southwestern Medical Center at Dallas
Kathleen A Kennedy, MD, MPH, Principal Investigator, Affiliation: The University of Texas Health Science Center, Houston
Barbara Schmidt, MD, Principal Investigator, Affiliation: University of Pennsylvania
Carl T D'Angio, MD, Principal Investigator, Affiliation: University of Rochester
Uday Devaskar, MD, Principal Investigator, Affiliation: University of California, Los Angeles
Leif Nelin, MD, Principal Investigator, Affiliation: Research Institute at Nationwide Children's Hospital
William Truog, MD, Principal Investigator, Affiliation: Children's Mercy Hospital-Kansas City, MO

Overall contact:
Kristi L Watterberg, MD, Phone: 505-272-8609

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Primary outcome:

Efficacy

Safety

Secondary outcome:

Morbidity and Growth

Successful Extubation

Use of open-label dexamethasone

Respiratory status at 40 weeks

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. .

Minimum age: N/A. Maximum age: 30 Weeks. Gender(s): Both.

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

Kristi L Watterberg, MD, Phone: 505-272-8609

University of Alabama at Birmingham, Birmingham, Alabama 35233, United States; Recruiting
Waldemar A. Carlo, MD, Phone: 205-934-4680
Waldemar A. Carlo, MD, Principal Investigator

University of California - Los Angeles, Los Angeles, California 90025, United States; Recruiting
Uday Devaskar, MD, Phone: 310-825-9314
Uday Devaskar, MD, Principal Investigator

Stanford University, Palo Alto, California 94304, United States; Recruiting
Krisa P. Van Meurs, MD, Phone: 650-723-5711
Krisa P. Van Meurs, MD, Principal Investigator

Emory University, Atlanta, Georgia 30303, United States; Recruiting
Barbara J. Stoll, MD, Phone: 404-727-2456
Barbara J. Stoll, MD, Principal Investigator

Indiana University, Indianapolis, Indiana 46202, United States; Recruiting
Brenda B. Poindexter, MD MS, Phone: 317-274-4768
Brenda B. Poindexter, MD MS, Principal Investigator

University of Iowa, Iowa City, Iowa 52242, United States; Recruiting
Edward F. Bell, MD, Phone: 319-356-4006
Edward F. Bell, MD, Principal Investigator

Wayne State University, Detroit, Michigan 48201, United States; Recruiting
Seetha Shankaran, MD, Phone: 313-745-1436
Seetha Shankaran, MD, Principal Investigator

Children's Mercy Hospital, Kansas City, Missouri 64108, United States; Recruiting
William Truog, MD, Phone: 816-234-3592
William Truog, MD, Principal Investigator

University of New Mexico, Albuquerque, New Mexico 87131, United States; Recruiting
Kristi L. Watterberg, MD, Phone: 505-272-8609
Kristi L. Watterberg, MD, Principal Investigator

University of Rochester, Rochester, New York 14642, United States; Recruiting
Carl T D'Angio, MD, Phone: 585-273-4911
Carl T D'Angio, MD, Principal Investigator

Duke University, Durham, North Carolina 27710, United States; Recruiting
Ronald N. Goldberg, MD, Phone: 919-681-6024
Ronald N. Goldberg, MD, Principal Investigator
C. Michael Cotten, MD MHS, Sub-Investigator

RTI International, Durham, North Carolina 27705, United States; Active, not recruiting

Cincinnati Children's Medical Center, Cincinnati, Ohio 45267, United States; Recruiting
Kurt Schibler, MD, Phone: 513-636-3972
Kurt Schibler, MD, Principal Investigator

Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, United States; Recruiting
Michele C. Walsh, MD MS, Phone: 216-844-3387
Michele C. Walsh, MD MS, Principal Investigator

Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, United States; Recruiting
Leif Nelin, MD, Phone: 614-355-6724
Leif Nelin, MD, Principal Investigator

Univeristy of Pennsylvania, Philadelphia, Pennsylvania 19104, United States; Recruiting
Barbara Schmidt, MD, Phone: 215-662-3228
Barbara Schmidt, MD, Principal Investigator

Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island 02905, United States; Recruiting
Abbot R. Laptook, MD, Phone: 401-274-1122, Ext: 43200
Abbot R. Laptook, MD, Principal Investigator

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235, United States; Recruiting
Myra Wyckoff, MD, Phone: 214-648-3923
Pablo J. Sanchez, MD, Principal Investigator

University of Texas Health Science Center at Houston, Houston, Texas 77030, United States; Recruiting
Kathleen A. Kennedy, MD MPH, Phone: 713-500-6708
Kathleen A. Kennedy, MD MPH, Principal Investigator
Jon E. Tyson, MD MPH, Sub-Investigator

NICHD Neonatal Research Network site

Starting date: September 2011
Last updated: July 21, 2015