Early Blood Pressure Management in Extremely Premature Infants

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.

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