Hydrocortisone for BPD

NCT01353313 | Completed Phase 3 Results DMC FDA Drug

• 22 other identifiers: NICHD-NRN-0045U10HD034216U10HD027904U10HD021364U10HD027853U10HD040689U10HD040492U10HD027851U10HD021373U10HD027856U10HD053109U10HD036790U10HD027880U10HD053089U10HD021385U10HD068244U10HD068263U10HD068270U10HD068278U10HD068284U24HL1377291UG3HL137872
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 20

Brief Summary

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.

Conditions

Infant, Newborn; Infant, Small for Gestational Age; Infant, Very Low Birth Weight; Infant, Premature; Bronchopulmonary Dysplasia

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Survival Without Moderate/Severe Physiologic Bronchopulmonary Dysplasia (BPD)

  Survival without moderate or severe physiologic BPD at 36 weeks postmenstrual age. Moderate or severe physiologic BPD is defined as a requirement for supplemental oxygen and/or positive airway pressure to maintain oxygen saturation greater than 90 percent. A room air challenge was performed for infants estimated to be receiving less than 0.30 FiO2 by nasal cannula.

  From day of randomization to 36 weeks post menstrual age

• Survival Without Moderate/Severe Neurodevelopmental Impairment (NDI)

  Survival without moderate or severe neurodevelopmental impairment (NDI) at 22-26 months corrected age. NDI is defined as defined as any of: Bayley Scales of Infant and Toddler Development-III (Bayley-III) cognitive composite score less than 85 (standardized mean 100, SD 15, range 55-145) or motor composite score less than 85 (standardized mean 100, range 45-155) (lower scores indicating greater impairment), Gross Motor Function Classification System (GMFCS) level greater than or equal to II (on a scale from level I to V; I=normal and progressively higher levels indicate greater impairment), severe vision impairment in both eyes (consistent with refraction from less than 20 to 200), or bilateral hearing impairment with or without amplification (by report).

  From day of randomization to 22-26 months corrected age

Secondary Outcomes (38)

• Number of Participants With Successful Extubation

  From day of randomization to day 14 post randomization

• Total Deaths Before Discharge

  From day of randomization to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

• Number of Participants With Bronchopulmonary Dysplasia (BPD) Grade at 36 Weeks Postmenstrual Age

  At 36 weeks postmenstrual age

• Days of Mechanical Ventilation to 36 Weeks Postmenstrual Age (PMA)

  From birth to 36 weeks postmenstrual age

• Duration of Oxygen Supplementation up to Status

  From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Saline placebo

Drug: Placebo

Hydrocortisone

EXPERIMENTAL

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

Interventions

Hydrocortisone DRUG

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

Hydrocortisone

Placebo DRUG

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

Eligibility Criteria

• Age: Up to 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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 .

You may not qualify if:

• 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

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• National Center for Research Resources (NCRR): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (20)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California - Los Angeles

Los Angeles, California, 90025, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Univeristy of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (4)

• DeMauro SB, Kirpalani H, Hintz S, Watterberg KL, Watson V, Lowe J, Shankaran S, Chawla S, Vohr B, Msall ME, D'Angio CT, Yoder BA, Lai K, Winter S, Colaizy TT, Merhar SL, Ziolkowski K, Bann CM, Trotta M, Newman JE, Walsh MC, Higgins RD, Cahill TE, Duncan AF, Wilson-Costello DE, Peralta-Carcelen M, Arnold H, Mosquera RA, Heyne RJ, Fuller J, McGowan EC, Cavanaugh B, Harmon HM, Maitre NL, Neel ML, Van Meurs KP, Richards LA, Kilbride HW, Hines AC, Natarajan G, Trembath A, Benninger KL, Kesavan K, Malcolm WF, Zanger D, Reynolds AM, Carlson M, Das A; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Hydrocortisone in Preterm Infants and School-Age Functional Outcomes: Follow-Up of a Randomized Clinical Trial. JAMA Pediatr. 2025 Dec 8:e254801. doi: 10.1001/jamapediatrics.2025.4801. Online ahead of print.

  PMID: 41359352 DERIVED

• 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.

  PMID: 39543521 DERIVED

• 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.

  PMID: 37256621 DERIVED

• 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.

  PMID: 35320643 DERIVED

Related Links

• NICHD Neonatal Research Network site
• NICHD Pregnancy \& Perinatology Branch

MeSH Terms

Conditions

Premature Birth; Bronchopulmonary Dysplasia

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: Kristi Watterberg
• Organization: University of New Mexico Health Sciences

kwatterberg@salud.unm.edu

505-272-8609

Study Officials

• 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

• C. Michael Cotten, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• David Carlton, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Greg Sokol, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

• Abhik Das, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

• Krisa P Van Meurs, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Brenda P Poindexter, 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

  PRINCIPAL INVESTIGATOR

• Kristi L Watterberg, MD

  University of New Mexico

  STUDY CHAIR

• Myra Wyckoff, MD

  University of Texas, Southwestern Medical Center at Dallas

  PRINCIPAL INVESTIGATOR

• Jon E Tyson, MD, MPH

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

• Eric Eichenwald, 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

• Pablo J Sanchez, 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2011
• First Posted: May 13, 2011
• Study Start: August 11, 2011
• Primary Completion: September 21, 2020
• Study Completion: September 12, 2024
• Last Updated: February 27, 2025
• Results First Posted: August 19, 2022

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

US (20)