Inhaled Nitric Oxide (INO) for the Prevention of Bronchopulmonary Dysplasia (BPD) in Preterm Infants

Multi-center, double blind, placebo-controlled, randomized clinical trial. Infants who meet
all enrollment criteria at any point during days 5 to 14 after birth will be randomized to
inhaled NO starting at 20 ppm, or matching placebo, by means of a blinded INOvent® delivery
device. All infants will receive 24 days of therapy, following a dose reduction schedule.
Infants who are extubated before 24 days will continue therapy via nasal continuous positive
airway pressure (CPAP) or nasal cannula to complete 24 days' of therapy. The primary outcome
measure will be survival without BPD at 36 weeks gestational age using a physiologic
assessment of BPD.

Inclusion Criteria:

- Preterm infants who are:

1. 500 to 1250 grams at birth

2. < 30 weeks gestational age

3. 5 to 14 days of age (inclusive) at the time of entry

4. Requiring mechanical ventilation or for those infants ≤ 800 grams, positive
pressure support (including CPAP) for respiratory insufficiency on days 5 to 14
days of age (inclusive)

Exclusion Criteria:

1. Preterm infants with life-threatening anomalies (cranial, cardiac, thoracic,
chromosomal) or congenital diaphragmatic hernia with lung hypoplasia, or any subject
who will not receive complete intensive care

2. Preterm infants with bilateral Grade 4 intraventricular hemorrhage (IVH)

3. Subjects who are dependent on right to left shunting to maintain the systemic
circulation

4. Preterm infants who received prior iNO therapy

5. Use of another investigational agent