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Early Blood Pressure Management in Extremely Premature Infants

Phase 1
Completed
Conditions
Infant, Premature
Blood Pressure
Infant, Newborn
Infant, Low Birth Weight
Infant, Small for Gestational Age
Hypotension
Interventions
Drug: Infusion Placebo
Drug: Syringe Placebo
Registration Number
NCT00874393
Lead Sponsor
NICHD Neonatal Research Network
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
10
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 & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Placebo and PlaceboInfusion PlaceboDextrose (D5W) placebo AND normal saline placebo
Placebo and PlaceboSyringe PlaceboDextrose (D5W) placebo AND normal saline placebo
Dopamine and placeboSyringe PlaceboDopamine AND normal saline placebo
Placebo and hydrocortisoneInfusion PlaceboDextrose (D5W) placebo AND hydrocortisone
Dopamine and hydrocortisoneDopamineDopamine AND hydrocortisone
Dopamine and hydrocortisoneHydrocortisoneDopamine AND hydrocortisone
Placebo and hydrocortisoneHydrocortisoneDextrose (D5W) placebo AND hydrocortisone
Dopamine and placeboDopamineDopamine AND normal saline placebo
Primary Outcome Measures
NameTimeMethod
Enrollment and completion of 60 infants1 year
Secondary Outcome Measures
NameTimeMethod
Death1 week and prior to hospital discharge
Duration of antihypotensive therapyFirst 96 postnatal hours
Receipt and timing of medical and/or surgical therapy for a PDATo hospital discharge
Use of open-label antihypotensive therapies (inotropes, corticosteroids, blood and plasma volume expanders) for persistently low BP with biochemical evidence of poor perfusionFirst 96 postnatal hours
Spontaneous gastrointestinal perforationFirst 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

Trial Locations

Locations (17)

Yale University

🇺🇸

New Haven, Connecticut, United States

Wayne State University

🇺🇸

Detroit, Michigan, United States

RTI International

🇺🇸

Durham, North Carolina, United States

Cincinnati Children's Medical Center

🇺🇸

Cincinnati, Ohio, United States

University of Texas Southwestern Medical Center at Dallas

🇺🇸

Dallas, Texas, United States

University of Utah

🇺🇸

Salt Lake City, Utah, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

Duke University

🇺🇸

Durham, North Carolina, United States

University of New Mexico

🇺🇸

Albuquerque, New Mexico, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

University of Iowa

🇺🇸

Iowa City, Iowa, United States

Stanford University

🇺🇸

Palo Alto, California, United States

Case Western Reserve University

🇺🇸

Cleveland, Ohio, United States

Brown University, Women & Infants Hospital of Rhode Island

🇺🇸

Providence, Rhode Island, United States

University of Texas Health Science Center at Houston

🇺🇸

Houston, Texas, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

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