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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
  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:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

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 2018
Estimated Primary Completion Date: August 2016 (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


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
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 Recruiting
Los Angeles, California, United States, 90025
Contact: Uday Devaskar, MD    310-825-9314      
Principal Investigator: Uday Devaskar, MD         
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 Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Brenda B. Poindexter, MD MS    317-274-4768      
Principal Investigator: Brenda B. Poindexter, MD MS         
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 Recruiting
Detroit, Michigan, United States, 48201
Contact: Seetha Shankaran, MD    313-745-1436      
Principal Investigator: Seetha Shankaran, MD         
United States, Missouri
Children's Mercy Hospital Recruiting
Kansas City, Missouri, United States, 64108
Contact: William Truog, MD    816-234-3592      
Principal Investigator: William Truog, MD         
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         
Sponsors and Collaborators
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 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
  More Information

Additional Information:
No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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: October 28, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Very Low Birth Weight (VLBW)
Prematurity
Mechanical ventilation
Intubation
Neurodevelopmental impairment

Additional relevant MeSH terms:
Infant, Newborn, Diseases
Infant, Premature, Diseases
Birth Weight
Bronchopulmonary Dysplasia
Body Weight
Lung Diseases
Lung Injury
Respiratory Tract Diseases
Signs and Symptoms
Ventilator-Induced Lung Injury
Cortisol succinate
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Dermatologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014