Inhaled Nitric Oxide Study for Respiratory Failure in Newborns

Respiratory failure in term newborns is associated with significant morbidity and mortality,
despite maximal conventional therapy. Neonates with pulmonary hypertension have been treated
with iNO, a selective pulmonary vasodilator. This multicenter, double-masked
placebo-controlled randomized trial tested whether iNO would reduce the risk of death and/or
the initiation of extracorporeal membrane oxygenation (ECMO) in a prospectively defined
cohort of term or near-term neonates with hypoxic respiratory failure unresponsive to
conventional therapy. The sample size was based on a reduction of the primary event (death or
ECMO) from 50 percent to 30 percent; 90 percent power; and a two-tailed Type I error of 0.05.

Infants were evaluated at baseline for pulmonary, cardiac, bleeding status, and therapies
received. Those who were greater than 34 wks gestation and 14 days old or less and required
assisted ventilation with an OI (mean airway pressure x FiO2 divided by the PaO2 x 100)
greater than 25 were eligible. They were randomly assigned to receive iNO at 20 ppm or 100
percent oxygen as a control. Infants whose PaO2 increased by less than 20 mm Hg after 30
minutes were studied at 80ppm iNO or control gas.; MetHg and NO2 concentrations were
monitored regularly. Management, including surfactant administration, included prospectively
defined criteria for study gas response, escalation, reinitiation, and weaning. The maximum
total time on study gas was 336 hrs (after 240 hrs, the INO concentration was required to be
no more than 5 ppm). Patients were followed to death, discharge, or 120 days and evaluated at
18-24 mos by a masked certified examiner.

Inclusion Criteria:

- Greater than 34 wks gestational age

- One or more of the following diagnoses: primary pulmonary hypertension of the newborn,
respiratory distress syndrome, perinatal aspiration syndrome, pneumonia/sepsis,
suspected pulmonary hypoplasia

- Oxygenation Index (OI) greater than 15 and less than 25 on 2 arterial blood gases at
least 15 min apart

- Indwelling arterial line

- Echocardiography before randomization

- Parental consent

Exclusion Criteria:

- Congenital diaphragmatic hernia

- Known congenital heart disease

- Decision not to provide full therapy