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Hydrocortisone for BPD

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01353313
First received: April 20, 2011
Last updated: October 28, 2014
Last verified: August 2014

April 20, 2011
October 28, 2014
September 2011
August 2016   (final data collection date for primary outcome measure)
  • 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
Complete list of historical versions of study NCT01353313 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
 
Hydrocortisone for BPD
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

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.

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. .

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
800
December 2018
August 2016   (final data collection date for primary outcome measure)

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
Both
up to 30 Weeks
No
Contact: Kristi L Watterberg, MD 505-272-8609
Contact: Rosemary D Higgins, MD (301) 496-5575
United States
 
NCT01353313
NICHD-NRN-0045, U10HD034216, U10HD027904, U10HD021364, U10HD027853, U10HD040689, U10HD040492, U10HD027851, U10HD021373, U10HD027856, U10HD053109, U10HD036790, U10HD027880, U10HD053089, U10HD021385, U10HD068244, U10HD068263, U10HD068270, U10HD068278, U10HD068284
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Research Resources (NCRR)
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: Ron N Goldberg, MD Duke University
Principal Investigator: Barbara J Stoll, MD Emory University
Principal Investigator: Brenda B Poindexter, MD, MS Indiana University
Principal Investigator: Abhik Das, PhD RTI International
Principal Investigator: Krisa P Van Meurs, MD Stanford University
Principal Investigator: Kurt Schibler, MD Cincinnati Children's Medical Center
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: Pablo J Sanchez, MD University of Texas Southwestern Medical Center at Dallas
Principal Investigator: Kathleen A Kennedy, MD, MPH The University of Texas Health Science Center, Houston
Principal Investigator: Barbara Schmidt, 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: Leif Nelin, MD Research Institute at Nationwide Children's Hospital
Principal Investigator: William Truog, MD Children's Mercy Hospital-Kansas City, MO
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP