Early Blood Pressure Management in Extremely Premature Infants

Condition(s) targeted: Infant, Newborn; Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature; Hypotension; Blood Pressure

Intervention: Dopamine (Drug); Hydrocortisone (Drug); Infusion Placebo (Drug); Syringe Placebo (Drug)

Phase: N/A

Status: Completed

Sponsored by: NICHD Neonatal Research Network

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

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.

Official title: Early Blood Pressure Management in Extremely Preterm Infants Feasibility Pilot Study

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Enrollment and completion of 60 infants

Secondary outcome:

Death

Duration of antihypotensive therapy

Receipt and timing of medical and/or surgical therapy for a PDA

Use of open-label antihypotensive therapies (inotropes, corticosteroids, blood and plasma volume expanders) for persistently low BP with biochemical evidence of poor perfusion

Spontaneous gastrointestinal perforation

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)

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.

Minimum age: N/A. Maximum age: 24 Hours. Gender(s): Both.

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

University of Alabama at Birmingham, Birmingham, Alabama 35233, United States

Stanford University, Palo Alto, California 94304, United States

Yale University, New Haven, Connecticut 06504, United States

Emory University, Atlanta, Georgia 30303, United States

Indiana University, Indianapolis, Indiana 46202, United States

University of Iowa, Iowa City, Iowa 52242, United States

Tufts Medical Center, Boston, Massachusetts 02111, United States

Wayne State University, Detroit, Michigan 48201, United States

University of New Mexico, Albuquerque, New Mexico 87131, United States

Duke University, Durham, North Carolina 27710, United States

RTI International, Durham, North Carolina 27705, United States

Cincinnati Children's Medical Center, Cincinnati, Ohio 45267, United States

Case Western Reserve University, Cleveland, Ohio 44106, United States

Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island 02905, United States

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235, United States

University of Texas Health Science Center at Houston, Houston, Texas 77030, United States

University of Utah, Salt Lake City, Utah 84108, United States

NICHD Neonatal Research Network

Starting date: July 2009
Last updated: July 24, 2015