Examining the Use of Non-Invasive Inhaled Nitric Oxide to Reduce Chronic Lung Disease in Premature Newborns

BPD is a serious lung condition that primarily affects premature newborns and newborns with
low birth weights. iNO has been proven to be a safe and effective treatment for pulmonary
hypertension and hypoxemic respiratory failure—both of which are abnormal lung conditions—in
full-term newborns. However, in babies born prematurely, the effects of iNO on lung function
are not well defined. Also, previous studies have mainly examined whether iNO reduces the
incidence of BPD in newborns who are on mechanical ventilation. However, intubation and
mechanical ventilation of premature newborns is now increasingly being avoided, and
non-invasive support, including the use of nasal continuous positive airway pressure
(NCPAP), is being used. Early treatment with low-dose iNO may reduce the incidence of BPD in
premature newborns who do not require mechanical ventilation and intubation after delivery.
The purpose of this study is to determine if low-dose, non-invasive iNO reduces the risk of
BPD, pulmonary hypertension, and death in premature newborns who do not require mechanical
ventilation.

This study will enroll premature newborns who require extra oxygen but do not require
intubation or mechanical ventilation for respiratory failure in the first 72 hours of life.
Participants will be randomly assigned to receive low-dose, non-invasive iNO or nitrogen
(placebo) during their hospital stay. While hospitalized, participants' heart rate, blood
oxygen level breathing rate, blood pressure, and medications will be monitored, and blood
collection will occur at various times. Monitoring will continue until participants are 30
weeks corrected gestational age or for at least 14 days if participants are born at 29 weeks
or more. All participants will undergo an ultrasound of the head when they are 7 days, 28
days, and 36 weeks of age. They will undergo an echocardiogram, which is an ultrasound of
the heart, at 7 and 21 days of age and 4 weeks before the original expected due date. A
chest x-ray will be performed before hospital discharge, and a breathing status test will be
performed either 4 weeks before participants' original expected due date or before hospital
discharge. Follow-up study visits will occur at Years 1 and 2, and will include a physical
examination and developmental and behavioral testing. Another echocardiogram will also be
performed at the Year 1 visit.

Inclusion Criteria:

- Birth weight of 500-1250 grams and gestational age of less than 34 weeks

- Age at enrollment is less than 72 hours

- Supplemental oxygen or 21% requirement by nasal cannula or NCPAP only

Exclusion Criteria:

- Presence of structural heart disease (other than patent ductus arteriosus, atrial
septal defect less than 1 cm, or muscular ventricular septal defect less than 2 mm)

- Presence of lethal congenital anomaly

- Participating in another concurrent experimental study

- Requires mechanical ventilation in the first 72 hours of life (patients are not
excluded if they are intubated briefly BUT they must be extubated at the time of
consent and study entry prior to 72 hours of life)