Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
800 participants
INTERVENTIONAL
2011-08-11
2024-09-12
Brief Summary
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Detailed Description
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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.
2. 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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
TRIPLE
Study Groups
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Placebo
Saline placebo
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
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)
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
Interventions
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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
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
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
30 Weeks
ALL
No
Sponsors
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National Center for Research Resources (NCRR)
NIH
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
National Heart, Lung, and Blood Institute (NHLBI)
NIH
National Center for Advancing Translational Sciences (NCATS)
NIH
NICHD Neonatal Research Network
NETWORK
Responsible Party
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Principal Investigators
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Michele C Walsh, MD
Role: PRINCIPAL_INVESTIGATOR
Case Western Reserve University, Rainbow Babies and Children's Hospital
Seetha Shankaran, MD
Role: PRINCIPAL_INVESTIGATOR
Wayne State University
Abbot R Laptook, MD
Role: PRINCIPAL_INVESTIGATOR
Brown University, Women & Infants Hospital of Rhode Island
C. Michael Cotten, MD
Role: PRINCIPAL_INVESTIGATOR
Duke University
David Carlton, MD
Role: PRINCIPAL_INVESTIGATOR
Emory University
Greg Sokol, MD
Role: PRINCIPAL_INVESTIGATOR
Indiana University
Abhik Das, PhD
Role: PRINCIPAL_INVESTIGATOR
RTI International
Krisa P Van Meurs, MD
Role: PRINCIPAL_INVESTIGATOR
Stanford University
Brenda P Poindexter, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Hospital Medical Center, Cincinnati
Waldemar A Carlo, MD
Role: PRINCIPAL_INVESTIGATOR
University of Alabama at Birmingham
Edward F Bell, MD
Role: PRINCIPAL_INVESTIGATOR
University of Iowa
Kristi L Watterberg, MD
Role: STUDY_CHAIR
University of New Mexico
Myra Wyckoff, MD
Role: PRINCIPAL_INVESTIGATOR
University of Texas, Southwestern Medical Center at Dallas
Jon E Tyson, MD, MPH
Role: PRINCIPAL_INVESTIGATOR
The University of Texas Health Science Center, Houston
Eric Eichenwald, MD
Role: PRINCIPAL_INVESTIGATOR
University of Pennsylvania
Carl T D'Angio, MD
Role: PRINCIPAL_INVESTIGATOR
University of Rochester
Uday Devaskar, MD
Role: PRINCIPAL_INVESTIGATOR
University of California, Los Angeles
Pablo J Sanchez, MD
Role: PRINCIPAL_INVESTIGATOR
Research Institute at Nationwide Children's Hospital
William Truog, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Mercy Hospital Kansas City
Bradley Yoder, MD
Role: PRINCIPAL_INVESTIGATOR
University of Utah
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
University of California - Los Angeles
Los Angeles, California, United States
Stanford University
Palo Alto, California, United States
Emory University
Atlanta, Georgia, United States
Indiana University
Indianapolis, Indiana, United States
University of Iowa
Iowa City, Iowa, United States
Wayne State University
Detroit, Michigan, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
University of New Mexico
Albuquerque, New Mexico, United States
University of Rochester
Rochester, New York, United States
RTI International
Durham, North Carolina, United States
Duke University
Durham, North Carolina, United States
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States
Research Institute at Nationwide Children's Hospital
Columbus, Ohio, United States
Univeristy of Pennsylvania
Philadelphia, Pennsylvania, United States
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States
University of Texas Health Science Center at Houston
Houston, Texas, United States
University of Utah
Salt Lake City, Utah, United States
Countries
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References
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DeMauro SB, Kirpalani H, Ziolkowski K, Hintz S, Watterberg K, Lowe J, Shankaran S, Chawla S, Vohr B, Msall M, D'Angio C, Yoder BA, Lai K, Winter S, Colaizy T, Merhar S, Bann CM, Trotta M, Newman J, Natarajan A, Das A. The HYdrocortisone for Bronchopulmonary Dysplasia Respiratory and Developmental (HYBRiD) outcomes study: protocol for a longitudinal cohort study. BMC Pediatr. 2024 Nov 14;24(1):737. doi: 10.1186/s12887-024-05198-9.
Gentle SJ, Rysavy MA, Li L, Laughon MM, Patel RM, Jensen EA, Hintz S, Ambalavanan N, Carlo WA, Watterberg K; National Institute of Child Health and Human Development Neonatal Research Network. Heterogeneity of Treatment Effects of Hydrocortisone by Risk of Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants in the National Institute of Child Health and Human Development Neonatal Research Network Trial: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 May 1;6(5):e2315315. doi: 10.1001/jamanetworkopen.2023.15315.
Watterberg KL, Walsh MC, Li L, Chawla S, D'Angio CT, Goldberg RN, Hintz SR, Laughon MM, Yoder BA, Kennedy KA, McDavid GE, Backstrom-Lacy C, Das A, Crawford MM, Keszler M, Sokol GM, Poindexter BB, Ambalavanan N, Hibbs AM, Truog WE, Schmidt B, Wyckoff MH, Khan AM, Garg M, Chess PR, Reynolds AM, Moallem M, Bell EF, Meyer LR, Patel RM, Van Meurs KP, Cotten CM, McGowan EC, Hines AC, Merhar S, Peralta-Carcelen M, Wilson-Costello DE, Kilbride HW, DeMauro SB, Heyne RJ, Mosquera RA, Natarajan G, Purdy IB, Lowe JR, Maitre NL, Harmon HM, Hogden LA, Adams-Chapman I, Winter S, Malcolm WF, Higgins RD; Eunice Kennedy Shriver NICHD Neonatal Research Network. Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia. N Engl J Med. 2022 Mar 24;386(12):1121-1131. doi: 10.1056/NEJMoa2114897.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Related Links
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NICHD Neonatal Research Network site
NICHD Pregnancy \& Perinatology Branch
Other Identifiers
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NICHD-NRN-0045
Identifier Type: -
Identifier Source: org_study_id
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