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

Early Blood Pressure Management in Extremely Preterm Infants Feasibility Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Blood Pressure; Hypotension; Infant, Small for Gestational Age; Infant, Premature; Infant, Low Birth Weight; Infant, Newborn
• Intervention / Treatment: Drug: Dopamine; Drug: Hydrocortisone; Drug: Syringe Placebo; Drug: Infusion Placebo

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
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Connecticut
    • New Haven, Connecticut, United States, 06504
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Durham, North Carolina, United States, 27705
      • RTI International
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Cincinnati Children's Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Brown University, Women & Infants Hospital of Rhode Island
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 day (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dopamine and hydrocortisone; Dopamine AND hydrocortisone	Drug: Dopamine; Dopamine; Drug: Hydrocortisone; Hydrocortisone
Active Comparator: Dopamine and placebo; Dopamine AND normal saline placebo	Drug: Dopamine; Dopamine; Drug: Syringe Placebo; Normal saline
Active Comparator: Placebo and hydrocortisone; Dextrose (D5W) placebo AND hydrocortisone	Drug: Hydrocortisone; Hydrocortisone; Drug: Infusion Placebo; Dextrose (D5W)
Placebo Comparator: Placebo and Placebo; Dextrose (D5W) placebo AND normal saline placebo	Drug: Syringe Placebo; Normal saline; Drug: Infusion Placebo; Dextrose (D5W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Enrollment and completion of 60 infants	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Death	1 week and prior to hospital discharge
Duration of antihypotensive therapy	First 96 postnatal hours
Receipt and timing of medical and/or surgical therapy for a PDA	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	First 96 postnatal hours
Spontaneous gastrointestinal perforation	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)	To hospital discharge

Collaborators and Investigators

• Sponsor: NICHD Neonatal Research Network
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Beau J. Batton, MD, Case Western Reserve University, Rainbow Babies and Children's Hospital; Principal Investigator: Abbot R. Laptook, MD, Brown University; Principal Investigator: Brenda P. Poindexter, MD MS, Indiana University; Principal Investigator: Pablo J. Sanchez, MD, University of Texas; Principal Investigator: Ivan D. Franz III, MD, Tufts University

Publications and helpful links

General 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.

Helpful Links

• NICHD Neonatal Research Network

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: April 1, 2009
• First Submitted That Met QC Criteria: April 1, 2009
• First Posted (Estimate): April 2, 2009

Study Record Updates

• Last Update Posted (Actual): May 25, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Dopamine; Prematurity; Hydrocortisone; NICHD Neonatal Research Network; Very Low Birth Weight (VLBW); Extremely Low Birth Weight (ELBW); Blood Pressure Management
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Body Weight; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Birth Weight; Hypotension; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Protective Agents; Cardiotonic Agents; Dopamine Agents; Sympathomimetics; Hydrocortisone; Dopamine
• Other Study ID Numbers: NICHD-NRN-0041; U10HD036790 (U.S. NIH Grant/Contract); U10HD021364 (U.S. NIH Grant/Contract); U10HD021373 (U.S. NIH Grant/Contract); U10HD021385 (U.S. NIH Grant/Contract); U10HD027851 (U.S. NIH Grant/Contract); U10HD027853 (U.S. NIH Grant/Contract); U10HD027856 (U.S. NIH Grant/Contract); U10HD027871 (U.S. NIH Grant/Contract); U10HD027880 (U.S. NIH Grant/Contract); U10HD027904 (U.S. NIH Grant/Contract); U10HD034216 (U.S. NIH Grant/Contract); U10HD040492 (U.S. NIH Grant/Contract); U10HD040689 (U.S. NIH Grant/Contract); U10HD053089 (U.S. NIH Grant/Contract); U10HD053109 (U.S. NIH Grant/Contract); U10HD053119 (U.S. NIH Grant/Contract); U10HD053124 (U.S. NIH Grant/Contract); UL1RR024139 (U.S. NIH Grant/Contract); UL1RR025744 (U.S. NIH Grant/Contract); UL1RR024979 (U.S. NIH Grant/Contract); UL1RR025764 (U.S. NIH Grant/Contract); UL1RR025777 (U.S. NIH Grant/Contract); UL1RR025008 (U.S. NIH Grant/Contract); UL1RR025747 (U.S. NIH Grant/Contract)