NCT00005773

Early Inhaled Nitric Oxide for Respiratory Failure in Newborns

Early Inhaled Nitric Oxide Therapy in Term and Near Term Infants With Respiratory Failure

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 302 (actual)
• Sponsor: NICHD Neonatal Research Network · Network
• Sex: All
• Age: 14 Days
• Healthy volunteers: Not accepted

Summary

This prospective, randomized controlled trial tested whether initiating iNO therapy earlier would reduce death and reduce the use of extracorporeal membrane oxygenation (ECMO) -- temporary lung bypass -- therapy compared with the standard recommendation threshold. Infants who were born at \>34 weeks' gestation were enrolled when they required assisted ventilation and had an oxygenation index (OI) \>15 and \<25 on any 2 measurements in a 12-hour interval. Infants were randomized to receive either early iNO or to simulated initiation of iNO (control). Infants who had an increase in OI to 25 or more were given iNO as standard therapy. The neurodevelopment of the subjects were evaluated at 18-22 months corrected age.

Detailed description

Respiratory failure occurs in near term and term infants as a complication of perinatal aspiration syndromes, pneumonia, sepsis, respiratory distress syndrome and primary pulmonary hypertension. Recently a collaborative trial of the NICHD Neonatal Research Network and the Canadian Inhaled Nitric Oxide Study Group (the NINOS trial) demonstrated that inhaled nitric oxide (iNO) reduced the number of deaths and the need for extracorporeal membrane oxygenation (ECMO) therapy -- a lung bypass mechanism -- from 64 percent to 46 percent. The standard recommended threshold for initiation of iNO therapy, based on this trial, was an oxygenation index (OI) \>=25. The purpose of this study is to determine if administration of inhaled nitric oxide earlier in the course of respiratory failure and to infants with less severe respiratory failure, decreases the incidence of ECMO or death, as suggested by the sub-group analysis of the original NINOS trial. This prospective, randomized controlled trial tested whether initiating iNO therapy earlier would reduce death and reduce the use of ECMO therapy compared with the standard recommendation threshold. Infants who were born at \>34 weeks' gestation (near- or full-term) were enrolled when they required assisted ventilation and had an oxygenation index (OI) \>15 and \<25 on any 2 measurements in a 12-hour interval. Infants were randomized to receive either early iNO or to simulated initiation of iNO (control). Infants who had an increase in OI to 25 or more were given iNO as standard therapy. The neurodevelopment of the subjects were evaluated at 18-22 months corrected age. The study compared the outcome of infants received iNO at OI \>15 and \<25, with a control group that received a simulated early procedure with iNO actually given based on the standard recommendation. iNO was delivered at 20 ppm during the initial dose-response evaluation. Infants in either group who showed subsequent deterioration with OI \>25 on two consecutive measurements at least one hour apart, or a rapid deterioration with OI \>30 on two consecutive measurements 15 minutes apart, received iNO therapy as part of standard medical management. Specific guidelines were followed for the use of high frequency ventilation and surfactant during study gas administration to prevent them from confounding the results of the study. Study recruitment was discontinued after 3 years due to a persistent decline in enrollment. Infants were given neurodevelopmental exams at 18-22 months corrected age.

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	Study gas was initiated at a concentration of 5 ppm, and the dose was increased to 20 ppm when the infant had \<=20 mm Hg increase in PaO2 (less than full response).
DRUG	Standard iNO therapy	Begin a sham initiation of iNO in term and near-term infants in respiratory failure with an oxygenation index (OI) between 15-25; initiated actual iNO therapy based on standard threshold (OI \>=25).

Timeline

• Start date: 1998-08-01
• Primary completion: 2001-05-01
• Completion: 2003-08-01
• First posted: 2000-06-02
• Last updated: 2017-09-26

Locations

18 sites across 1 country: United States