Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure

This multicenter, randomized, double-masked, controlled clinical trial evaluated the efficacy
of inhaled nitric oxide (iNO) in the treatment of the preterm infant with respiratory failure
secondary to respiratory distress syndrome (RDS), sepsis/pneumonia, aspiration syndrome,
idiopathic pulmonary hypertension and/or suspected pulmonary hypoplasia.

Infants were followed until death or discharge to home. The trial compared iNO therapy to
mock gas delivery as the control, and otherwise incorporated conventional management
strategies (including treatment with surfactant and high frequency ventilation as adjuncts to
iNO therapy).

During the initial dosing, iNO was started at 5 ppm and could be increased to 10 ppm. If the
infant did not respond, study gas was discontinued. For infants who responded to study gas, a
gradual weaning was initiated. The total exposure to study gas did not exceed 336 hours (14
days). Infants were monitored for signs of toxicity.

Medical and neurodevelopmental outcome of surviving infants were assessed at 18 to 22 months
corrected age by masked, certified examiners.

Inclusion Criteria

- Any infant with a birth weight 401 - 1500 grams and < 34 weeks gestational age with an
OI (mean Paw x FiO2 x 100/PaO2) > 10 on two consecutive blood gases at least 30
minutes apart, but no more than 12 hours apart.

or

- Infants > 1500 grams and < 34 weeks gestational age will be entered in the Larger
Preemie Pilot Study if they have an OI greater than or equal to 15 on two consecutive
blood gases at least 30 minutes apart, but no more than 12 hours apart.

- Infants requiring assisted ventilation with a diagnosis of RDS/HMD, pneumonia and/or
sepsis, aspiration syndrome, idiopathic pulmonary hypertension, or suspected pulmonary
hypoplasia associated with PROM and/or oligohydramnios.

- Greater than or equal to 4 hours after one dose of surfactant.

- Less than or equal to 120 hours of age.

- All infants must have an indwelling arterial line.

Exclusion Criteria

- Any infant in whom a decision has been made not to provide full treatment (e.g.
chromosomal anomalies or severe birth asphyxia).

- Known structural congenital heart disease, except patent ductus arteriosus and
atrial-level shunts.

- Infants with any major abnormality involving the respiratory system such as congenital
diaphragmatic hernia, tracheoesophageal fistula or cystic fibrosis.

- Any bleeding diathesis considered to be clinically significant or thrombocytopenia
with platelet count < 50,000.

- Prior enrollment into a conflicting clinical trial such as the Neonatal Network
Surfactant CPAP trial.Inclusion Criteria