Inhaled Nitric Oxide Study for Respiratory Failure in Newborns

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: Inhaled nitric oxide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 14 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled Nitric Oxide<br>Inhaled Nitric Oxide (iNO) | Drug: Inhaled nitric oxide<br>* Inhaled Nitric oxide at a concentration of 20 ppm<br>|
| Placebo Comparator: Oxygen<br>100% oxygen | Drug: Placebo<br>* 100% Oxygen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or initiation of ECMO |  | Before hospital discharge or 120 days of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient |  | 30 minutes after drug administration | 
| Neurodevelopmental outcome |  | 18-22 Months Corrected Age | 
| Duration of hospital stay |  | At hospital discharge | 
| Duration of assisted ventilation, air leaks, or chronic lung disease |  | At hospital discharge | 
| Transfers for ECMO |  | At hospital discharge | 
| Meeting ECMO criteria |  | At hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nitric oxide, NICHD Neonatal Research Network, Hypertension, pulmonary, Hypoxic respiratory failure, Meconium aspiration, Methemoglobinemia, Oxygen inhalation therapy, Persistent Fetal Circulation Syndrome, Pneumonia, aspiration, Respiratory distress syndrome, Respiratory insufficiency, Severe respiratory failure