NCT00005776

Inhaled Nitric Oxide Study for Respiratory Failure in Newborns

The Randomized Inhaled Nitric Oxide Study (NINOS) in Full-Term and Nearly Full-Term Infants With Hypoxic Respiratory Failure

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 235 (actual)
• Sponsor: NICHD Neonatal Research Network · Network
• Sex: All
• Age: 14 Days
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Infant, Newborn
• Hypertension, Pulmonary
• Persistent Fetal Circulation Syndrome
• Pneumonia, Aspiration
• Respiratory Distress Syndrome, Newborn
• Respiratory Insufficiency

Interventions

Type	Name	Description
DRUG	Inhaled nitric oxide	Inhaled Nitric oxide at a concentration of 20 ppm
DRUG	Placebo	100% Oxygen

Timeline

• Start date: 1995-10-01
• Primary completion: 1996-05-01
• Completion: 1998-05-01
• First posted: 2000-06-02
• Last updated: 2017-09-26

Locations

20 sites across 2 countries: United States, Canada