Hydrocortisone for BPD - Full Text View

Purpose

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.

Condition	Intervention	Phase
Infant, Newborn Infant, Small for Gestational Age Infant, Very Low Birth Weight Infant, Premature Bronchopulmonary Dysplasia	Drug: Hydrocortisone Drug: Placebo	Phase 3


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

Resource links provided by NLM:

MedlinePlus related topics: Birth Weight Body Weight

Drug Information available for: Hydrocortisone acetate Hydrocortisone Hydrocortisone sodium succinate Hydrocortisone cypionate Hydrocortisone valerate Hydrocortisone probutate Proctofoam-HC

Genetic and Rare Diseases Information Center resources: Bronchopulmonary Dysplasia

U.S. FDA Resources

Further study details as provided by NICHD Neonatal Research Network:

Primary Outcome Measures:

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

Secondary Outcome Measures:

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 ]


Estimated Enrollment:	800
Study Start Date:	September 2011
Estimated Study Completion Date:	December 2019
Estimated Primary Completion Date:	August 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo Saline placebo	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
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)	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

Arms

Assigned Interventions

Placebo Comparator: Placebo

Saline placebo

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

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)

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

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. .

Eligibility


Ages Eligible for Study:	up to 30 Weeks (Child)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01353313

Contacts


Contact: Kristi L Watterberg, MD	505-272-8609
Contact: Rosemary D Higgins, MD	(301) 496-5575

Locations


United States, Alabama
University of Alabama at Birmingham	Recruiting
Birmingham, Alabama, United States, 35233
Contact: Waldemar A. Carlo, MD 205-934-4680
Principal Investigator: Waldemar A. Carlo, MD
United States, California
University of California - Los Angeles	Active, not recruiting
Los Angeles, California, United States, 90025
Stanford University	Recruiting
Palo Alto, California, United States, 94304
Contact: Krisa P. Van Meurs, MD 650-723-5711
Principal Investigator: Krisa P. Van Meurs, MD
United States, Georgia
Emory University	Recruiting
Atlanta, Georgia, United States, 30303
Contact: Barbara J. Stoll, MD 404-727-2456
Principal Investigator: Barbara J. Stoll, MD
United States, Indiana
Indiana University	Active, not recruiting
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa	Recruiting
Iowa City, Iowa, United States, 52242
Contact: Edward F. Bell, MD 319-356-4006
Principal Investigator: Edward F. Bell, MD
United States, Michigan
Wayne State University	Active, not recruiting
Detroit, Michigan, United States, 48201
United States, Missouri
Children's Mercy Hospital	Active, not recruiting
Kansas City, Missouri, United States, 64108
United States, New Mexico
University of New Mexico	Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Kristi L. Watterberg, MD 505-272-8609
Principal Investigator: Kristi L. Watterberg, MD
United States, New York
University of Rochester	Recruiting
Rochester, New York, United States, 14642
Contact: Carl T D'Angio, MD 585-273-4911
Principal Investigator: Carl T D'Angio, MD
United States, North Carolina
RTI International	Active, not recruiting
Durham, North Carolina, United States, 27705
Duke University	Recruiting
Durham, North Carolina, United States, 27710
Contact: Ronald N. Goldberg, MD 919-681-6024
Principal Investigator: Ronald N. Goldberg, MD
Sub-Investigator: C. Michael Cotten, MD MHS
United States, Ohio
Cincinnati Children's Medical Center	Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Kurt Schibler, MD 513-636-3972
Principal Investigator: Kurt Schibler, MD
Case Western Reserve University, Rainbow Babies and Children's Hospital	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Michele C. Walsh, MD MS 216-844-3387
Principal Investigator: Michele C. Walsh, MD MS
Research Institute at Nationwide Children's Hospital	Recruiting
Columbus, Ohio, United States, 43205
Contact: Leif Nelin, MD 614-355-6724
Principal Investigator: Leif Nelin, MD
United States, Pennsylvania
Univeristy of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Barbara Schmidt, MD 215-662-3228
Principal Investigator: Barbara Schmidt, MD
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island	Recruiting
Providence, Rhode Island, United States, 02905
Contact: Abbot R. Laptook, MD 401-274-1122 ext 43200
Principal Investigator: Abbot R. Laptook, MD
United States, Texas
University of Texas Southwestern Medical Center at Dallas	Recruiting
Dallas, Texas, United States, 75235
Contact: Myra Wyckoff, MD 214-648-3923
Principal Investigator: Pablo J. Sanchez, MD
University of Texas Health Science Center at Houston	Recruiting
Houston, Texas, United States, 77030
Contact: Kathleen A. Kennedy, MD MPH 713-500-6708
Principal Investigator: Kathleen A. Kennedy, MD MPH
Sub-Investigator: Jon E. Tyson, MD MPH
United States, Utah
University of Utah	Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Bradley Yoder, MD 801-581-7052
Principal Investigator: Bradley A. Yoder, MD

Sponsors and Collaborators

NICHD Neonatal Research Network

National Center for Research Resources (NCRR)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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:	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	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:	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
Principal Investigator:	Bradley Yoder, MD	University of Utah

More Information

Additional Information:

NICHD Neonatal Research Network site This link exits the ClinicalTrials.gov site


Responsible Party:	NICHD Neonatal Research Network
ClinicalTrials.gov Identifier:	NCT01353313 History of Changes
Other Study ID Numbers:	NICHD-NRN-0045 U10HD034216 U10HD027904 U10HD021364 U10HD027853 U10HD040689 U10HD040492 U10HD027851 U10HD021373 U10HD027856 U10HD053109 U10HD036790 U10HD027880 U10HD053089 U10HD021385 U10HD068244 U10HD068263 U10HD068270 U10HD068278 U10HD068284
Study First Received:	April 20, 2011
Last Updated:	July 29, 2016
Health Authority:	United States: Federal Government United States: Institutional Review Board

Keywords provided by NICHD Neonatal Research Network:


NICHD Neonatal Research Network Extremely Low Birth Weight (ELBW) Very Low Birth Weight (VLBW) Prematurity	Mechanical ventilation Intubation Neurodevelopmental impairment

Additional relevant MeSH terms:


Lung Diseases Respiratory Tract Diseases Infant, Premature, Diseases Infant, Newborn, Diseases Birth Weight Bronchopulmonary Dysplasia Body Weight Signs and Symptoms Ventilator-Induced Lung Injury Lung Injury Hydrocortisone 17-butyrate 21-propionate	Cortisol succinate Hydrocortisone acetate Hydrocortisone Benzyl Alcohol Anti-Inflammatory Agents Anesthetics, Local Anesthetics Central Nervous System Depressants Physiological Effects of Drugs Sensory System Agents Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 23, 2016