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

• Death [ Time Frame: 1 week and prior to hospital discharge ] [ Designated as safety issue: Yes ]
• Duration of antihypotensive therapy [ Time Frame: First 96 postnatal hours ] [ Designated as safety issue: Yes ]
• Receipt and timing of medical and/or surgical therapy for a PDA [ Time Frame: To hospital discharge ] [ Designated as safety issue: Yes ]
• 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 ] [ Designated as safety issue: Yes ]
• Spontaneous gastrointestinal perforation [ Time Frame: First 7 days ] [ Designated as safety issue: Yes ]
• 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 ] [ Designated as safety issue: Yes ]

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.

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.

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

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

• 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

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