Early Inhaled Nitric Oxide for Respiratory Failure in Newborns
- Conditions
- Pneumonia, AspirationRespiratory Distress Syndrome, NewbornHypertension, PulmonaryRespiratory InsufficiencyInfant, NewbornPersistent Fetal Circulation Syndrome
- Interventions
- Drug: Standard iNO therapyDrug: Inhaled Nitric Oxide
- Registration Number
- NCT00005773
- Lead Sponsor
- NICHD Neonatal Research Network
- Brief 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 302
- Infants born at >34 weeks gestational age
- Require assisted ventilation for hypoxic respiratory failure
- Have a diagnosis of primary persistent pulmonary hypertension (PPHN), respiratory distress syndrome, perinatal aspiration syndrome, pneumonia/sepsis, or suspected pulmonary hypoplasia
- Have an oxygenation index >15 and <25 based on 2 arterial blood gases taken at least 15 minutes apart or an Fi02 >80%
- In-dwelling arterial line
- Parental consent
- Known structural congenital heart disease, except patent ductus arteriosus and atrial level shunts
- Congenital diaphragmatic hernia
- Use of high frequency jet ventilation at the time of randomization
- Prior exposure to inhaled nitric oxide therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard iNO management 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). Early iNO Management Inhaled Nitric Oxide Initiation of iNO in use for term and near-term infants in respiratory failure with an oxygenation index between 15-25.
- Primary Outcome Measures
Name Time Method Death or use of extracorporeal membrane oxygenation (ECMO) Hospital discharge or 120 days of life
- Secondary Outcome Measures
Name Time Method Progression to severe respiratory failure (OI>40) Hospital discharge or 120 days of life Severe respiratory failure, defined as OI \>40
Use of iNO therapy based on the standard recommended threshold Hospital Discharge or 120 days of life Neurodevelopmental impairment 18-22 months corrected age
Trial Locations
- Locations (18)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Stanford University
🇺🇸Palo Alto, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
San Diego Children's Hospital
🇺🇸San Diego, California, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Case Western Reserve University, Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Cincinnati Children's Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
Brown University, Women & Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
University of Washington School of Medicine
🇺🇸Seattle, Washington, United States
St. Joseph's Hospital
🇺🇸Phoenix, Arizona, United States
Yale University
🇺🇸New Haven, Connecticut, United States
University of Miami
🇺🇸Miami, Florida, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
University of Tennessee
🇺🇸Memphis, Tennessee, United States