Early Blood Pressure Management in Extremely Premature Infants (ELGAN BP)

• ClinicalTrials.gov Identifier: NCT00874393
• Recruitment Status: Completed
• First Posted: April 2, 2009
• Last Update Posted: May 25, 2017
• Sponsor: NICHD Neonatal Research Network
• Collaborators: National Center for Research Resources (NCRR); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): NICHD Neonatal Research Network

Tracking Information

• First Submitted Date: April 1, 2009
• First Posted Date: April 2, 2009
• Last Update Posted Date: May 25, 2017
• Study Start Date: July 2009
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 1, 2009): Enrollment and completion of 60 infants [ Time Frame: 1 year ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 1, 2009)

• Death [ Time Frame: 1 week and prior to hospital discharge ]
• Duration of antihypotensive therapy [ Time Frame: First 96 postnatal hours ]
• Receipt and timing of medical and/or surgical therapy for a PDA [ Time Frame: To hospital discharge ]
• Use of open-label antihypotensive therapies (inotropes, corticosteroids, blood and plasma volume expanders) for persistently low BP with biochemical evidence of poor perfusion [ Time Frame: First 96 postnatal hours ]
• Spontaneous gastrointestinal perforation [ Time Frame: First 7 days ]
• In-hospital complications (grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis requiring surgical intervention, retinopathy of prematurity requiring laser surgery, or bronchopulmonary dysplasia) [ Time Frame: To hospital discharge ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Early Blood Pressure Management in Extremely Premature Infants
• Official Title: Early Blood Pressure Management in Extremely Preterm Infants Feasibility Pilot Study

Brief Summary

This trial tests the feasibility of enrolling 60 extremely preterm infants in a randomized, double-blinded study of blood pressure management within 12 months. Eligible infants will receive an infusion drug (dopamine or a dextrose placebo) and a syringe drug (hydrocortisone or a normal saline placebo).

Enrolled infants will be randomized to receive one of the following drug pairs:

• dopamine and hydrocortisone
• dopamine and normal saline
• dextrose and hydrocortisone
• dextrose and normal saline.

In addition to the intervention above, the NRN is conducting a 6-month time-limited prospective observational study of all infants born at an NRN center between 23 and 26 weeks gestational age. All clinical decisions made for these babies will be at the discretion of the attending neonatologist/infant care team according to standard practice at each institution. Data on blood pressure management in the first 24 postnatal hours collected for each infant.

Detailed Description

Since most extremely preterm infants are critically ill in the immediate postnatal period, establishing "normal" blood pressure (BP) values is difficult. This lack of data makes deciding when to institute therapy for hypotension (low BP) challenging, leading to considerable variability in BP management in neonatal intensive care units (NICUs). Despite a lack of data on safety or efficacy, as many as 64% of extremely preterm infants receive inotropes (e.g., dopamine), and up to 12.4% of very low birthweight infants receive hydrocortisone for perceived hypotension. Since both untreated low BP and therapy provided for low BP may be harmful, the decision of whether to treat is an important issue. To date, no prospective randomized, controlled trial of BP management in this population has been performed.

This trial tests the feasibility of enrolling up to 60 extremely preterm infants in a randomized, double-blinded study of blood pressure management within 12 months. It will enroll 60 infants between 23 0/7 and 26 6/7 weeks gestational age born at 6 participating NICHD Neonatal Research Network sites. Eligible infants will receive a study infusion drug (dopamine or a dextrose placebo) and a study syringe drug (hydrocortisone or a normal saline placebo). Infants will be randomized to receive one of the following drug pairs: (1) dopamine and hydrocortisone; (2) dopamine and a placebo (normal saline solution); (3) a placebo (dextrose) and hydrocortisone; or (4) placebo (dextrose) and placebo (normal saline). (NOTE: dopamine is normally mixed with dextrose and hydrocortisone is mixed with saline solution before being administered, which is why two different placebos are being used in this trial.)

The information gathered will provide a framework for the design of a potential larger, multi-centered, randomized control trial.

NOTE: The NICHD Neonatal Research Network has received a FDA exemption from the IND regulations for this trial.

In addition to the interventional trial above, the NRN is conducting a 6-month time-limited prospective observational study of all infants born at an NRN center between 23 and 26 weeks gestational age. All clinical decisions made for these babies will be at the discretion of the attending neonatologist/infant care team according to standard practice at each institution. Data on blood pressure management in the first 24 postnatal hours collected for each infant.

Based on slow rate of recruitment, a time-limited observational study of hypotension in ELBW infants has been added to the current study.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Infant, Newborn
• Infant, Low Birth Weight
• Infant, Small for Gestational Age
• Infant, Premature
• Hypotension
• Blood Pressure

Intervention

• Drug: Dopamine
  Dopamine
• Drug: Hydrocortisone
  Hydrocortisone
• Drug: Infusion Placebo
  Dextrose (D5W)
• Drug: Syringe Placebo
  Normal saline

Study Arms

• Active Comparator: Dopamine and hydrocortisone
  Dopamine AND hydrocortisone
  Interventions:

  • Drug: Dopamine
  • Drug: Hydrocortisone
• Active Comparator: Dopamine and placebo
  Dopamine AND normal saline placebo
  Interventions:

  • Drug: Dopamine
  • Drug: Syringe Placebo
• Active Comparator: Placebo and hydrocortisone
  Dextrose (D5W) placebo AND hydrocortisone
  Interventions:

  • Drug: Hydrocortisone
  • Drug: Infusion Placebo
• Placebo Comparator: Placebo and Placebo
  Dextrose (D5W) placebo AND normal saline placebo
  Interventions:

  • Drug: Infusion Placebo
  • Drug: Syringe Placebo

Publications *

• Batton BJ, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, Faix RG, Laughon MM, Van Meurs KP, Carlo WA, Higgins RD, Walsh MC; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Feasibility study of early blood pressure management in extremely preterm infants. J Pediatr. 2012 Jul;161(1):65-9.e1. doi: 10.1016/j.jpeds.2012.01.014. Epub 2012 Feb 14.
• Batton B, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, Faix RG, Laughon MM, Stoll BJ, Higgins RD, Walsh MC; Eunice Kennedy Shriver National Institute of Child Health & Human Development Neonatal Research Network. Early blood pressure, antihypotensive therapy and outcomes at 18-22 months' corrected age in extremely preterm infants. Arch Dis Child Fetal Neonatal Ed. 2016 May;101(3):F201-6. doi: 10.1136/archdischild-2015-308899. Epub 2015 Nov 13.
• Batton B, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, Faix RG, Laughon MM, Stoll BJ, Van Meurs KP, Carlo WA, Poindexter BB, Bell EF, Sanchez PJ, Ehrenkranz RA, Goldberg RN, Laptook AR, Kennedy KA, Frantz ID 3rd, Shankaran S, Schibler K, Higgins RD, Walsh MC; Eunice Kennedy Shriver National Institute of Child Health & Human Development Neonatal Research Network. Use of antihypotensive therapies in extremely preterm infants. Pediatrics. 2013 Jun;131(6):e1865-73. doi: 10.1542/peds.2012-2779. Epub 2013 May 6.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 29, 2012): 10
• Original Estimated Enrollment (submitted: April 1, 2009): 60
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Inborn infants
• 23 0/7 to 26 6/7 weeks estimated gestational age
• Umbilical arterial catheter in place at study entry
• <= 24 hours of age

Exclusion Criteria:

• Terminally ill infants
• Infants that have received (prior to enrollment): >20 ml/kg in fluid boluses, indomethacin, or ibuprofen
• Infants with major congenital anomalies

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 24 Hours (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00874393
• Other Study ID Numbers: NICHD-NRN-0041; U10HD021364 ( U.S. NIH Grant/Contract ); U10HD027880 ( U.S. NIH Grant/Contract ); U10HD034216 ( U.S. NIH Grant/Contract ); U10HD036790 ( U.S. NIH Grant/Contract ); U10HD040492 ( U.S. NIH Grant/Contract ); U10HD053089 ( U.S. NIH Grant/Contract ); U10HD053124 ( U.S. NIH Grant/Contract ); UL1RR025744 ( U.S. NIH Grant/Contract ); UL1RR025764 ( U.S. NIH Grant/Contract ); UL1RR025777 ( U.S. NIH Grant/Contract ); U10HD027904 ( U.S. NIH Grant/Contract ); U10HD027853 ( U.S. NIH Grant/Contract ); U10HD040689 ( U.S. NIH Grant/Contract ); U10HD027851 ( U.S. NIH Grant/Contract ); UL1RR025008 ( U.S. NIH Grant/Contract ); U10HD021373 ( U.S. NIH Grant/Contract ); U10HD027856 ( U.S. NIH Grant/Contract ); U10HD053109 ( U.S. NIH Grant/Contract ); UL1RR024979 ( U.S. NIH Grant/Contract ); U10HD053119 ( U.S. NIH Grant/Contract ); UL1RR025747 ( U.S. NIH Grant/Contract ); U10HD021385 ( U.S. NIH Grant/Contract ); U10HD027871 ( U.S. NIH Grant/Contract ); UL1RR024139 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: NICHD Neonatal Research Network
• Original Responsible Party: Beau Batton, MD, Study Principal Investigator, Case Western Reserve University, Rainbow Babies and Children's Hospital
• Current Study Sponsor: NICHD Neonatal Research Network
• Original Study Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborators

• National Center for Research Resources (NCRR)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Beau J. Batton, MD; Case Western Reserve University, Rainbow Babies and Children's Hospital
• Principal Investigator: Ronald N. Goldberg, MD; Duke University
• Principal Investigator: Krisa P. Van Meurs, MD; Stanford University
• Principal Investigator: Waldemar A Carlo, MD; University of Alabama at Birmingham
• Principal Investigator: Kristi L. Watterberg, MD; University of New Mexico
• Principal Investigator: Roger G. Faix, MD; University of Utah
• Principal Investigator: Abhik Das, PhD; RTI International
• Principal Investigator: Edward F. Bell, MD; University of Iowa
• Principal Investigator: Abbot R. Laptook, MD; Brown University
• Principal Investigator: Barbara J. Stoll, MD; Emory University
• Principal Investigator: Brenda P. Poindexter, MD MS; Indiana University
• Principal Investigator: Kurt Schibler, MD; Children's Hospital Medical Center, Cincinnati
• Principal Investigator: Kathleen A. Kennedy, MD MPH; The University of Texas Health Science Center, Houston
• Principal Investigator: Pablo J. Sanchez, MD; University of Texas
• Principal Investigator: Seetha Shankaran, MD; Wayne State University
• Principal Investigator: Richard A. Ehrenkranz, MD; Yale University
• Principal Investigator: Ivan D. Franz III, MD; Tufts University

• PRS Account: NICHD Neonatal Research Network
• Verification Date: May 2017