• Death or initiation of ECMO [ Time Frame: Before hospital discharge or 120 days of life ] [ Designated as safety issue: Yes ]
  

• PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient [ Time Frame: 30 minutes after drug administration ] [ Designated as safety issue: Yes ]
  
• Neurodevelopmental outcome [ Time Frame: 18-22 Months Corrected Age ] [ Designated as safety issue: No ]
  
• Duration of hospital stay [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]
  
• Duration of assisted ventilation, air leaks, or chronic lung disease [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]
  
• Transfers for ECMO [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]
  
• Meeting ECMO criteria [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]
  

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.