Respiratory failure in term newborns is associated with increased rates of death and long-term neurodevelopmental problems. This large international multicenter trial randomized newborns who had failed to respond to intensive care, including high levels of ventilator support, to receive either inhaled nitric oxide (iNO) or 100 percent oxygen to test whether iNO would decrease their risk of dying or requiring temporary lung bypass. Infants were followed during their initial hospitalization; their outcome was assessed at 18 to 24 mos of age.

Condition	Treatment or Intervention	Phase
Hypertension, Pulmonary Respiratory Insufficiency Infant, Newborn, Diseases Meconium Aspiration Persistent Fetal Circulation Syndrome Pneumonia, Aspiration Respiratory Distress Syndrome	Drug: Inhaled nitric oxide	Phase III

Further Study Details: 

Expected Total Enrollment:  235

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.

Ages Eligible for Study:  up to  14 Days,  Genders Eligible for Study:  Both

Criteria

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

Study chairs or principal investigators

Richard A. Ehrenkranz, MD,  Principal Investigator,  Yale University   
Neil N. Finer, MD,  Principal Investigator,  University of California, San Diego   

Study ID Numbers:  NICHD-1002; U10 HD21385; U10 HD34216; U10 HD34167; U10 HD21397; U10 HD27853; U10 HD27871; U10 HD21415; U10 HD27904; U10 HD27881; U10 HD27851; U10 HD27880; U10 HD21373; U01 HD19897; M01 RR08084; M01 RR06022; M01 RR00750; M01 RR00997; M01 RR00070; M01 RR01032
Record last reviewed:  April 2000
Last Updated:  October 13, 2004
Record first received:  June 1, 2000
ClinicalTrials.gov Identifier:  NCT00005776
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08