Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure

Study Overview
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Brief Summary
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This multicenter trial tested whether inhaled nitric oxide would reduce death or the need for oxygen in preterm infants (less than 34 weeks gestational age) with severe lung disease.

Detailed Description
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This multicenter, randomized, double-masked, controlled clinical trial evaluated the efficacy of inhaled nitric oxide (iNO) in the treatment of the preterm infant with respiratory failure secondary to respiratory distress syndrome (RDS), sepsis/pneumonia, aspiration syndrome, idiopathic pulmonary hypertension and/or suspected pulmonary hypoplasia. Infants were followed until death or discharge to home. The trial compared iNO therapy to mock gas delivery as the control, and otherwise incorporated conventional management strategies (including treatment with surfactant and high frequency ventilation as adjuncts to iNO therapy). During the initial dosing, iNO was started at 5 ppm and could be increased to 10 ppm. If the infant did not respond, study gas was discontinued. For infants who responded to study gas, a gradual weaning was initiated. The total exposure to study gas did not exceed 336 hours (14 days). Infants were monitored for signs of toxicity. Medical and neurodevelopmental outcome of surviving infants were assessed at 18 to 22 months corrected age by masked, certified examiners.

Official Title
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Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure

Conditions
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Sepsis, Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Respiratory Distress Syndrome (RDS), Pneumonia, Hypertension, Pulmonary

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 Any infant with a birth weight 401 - 1500 grams and < 34 weeks gestational age with an OI (mean Paw x FiO2 x 100/PaO2) > 10 on two consecutive blood gases at least 30 minutes apart, but no more than 12 hours apart. or Infants > 1500 grams and < 34 weeks gestational age will be entered in the Larger Preemie Pilot Study if they have an OI greater than or equal to 15 on two consecutive blood gases at least 30 minutes apart, but no more than 12 hours apart. Infants requiring assisted ventilation with a diagnosis of RDS/HMD, pneumonia and/or sepsis, aspiration syndrome, idiopathic pulmonary hypertension, or suspected pulmonary hypoplasia associated with PROM and/or oligohydramnios. Greater than or equal to 4 hours after one dose of surfactant. Less than or equal to 120 hours of age. All infants must have an indwelling arterial line. Exclusion Criteria Any infant in whom a decision has been made not to provide full treatment (e.g. chromosomal anomalies or severe birth asphyxia). Known structural congenital heart disease, except patent ductus arteriosus and atrial-level shunts. Infants with any major abnormality involving the respiratory system such as congenital diaphragmatic hernia, tracheoesophageal fistula or cystic fibrosis. Any bleeding diathesis considered to be clinically significant or thrombocytopenia with platelet count < 50,000. Prior enrollment into a conflicting clinical trial such as the Neonatal Network Surfactant CPAP trial.Inclusion Criteria

Ages Eligible for Study
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Maximum Age: 120 Hours

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled Nitric Oxide<br>Inhaled Nitric Oxide | Drug: Inhaled nitric oxide<br>* Started at 5 ppm and could be increased to 10 ppm<br>|
| Active Comparator: Placebo<br>Inhaled Oxygen | Drug: Placebo<br>* Started at 5 ppm and could be increased to 10 ppm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or Bronchopulmonary Dysplasia |  | At 36 weeks post-conceptional age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraventricular Hemorrhage Grade III and IV |  | At 36 weeks post-conceptional age | 
| Days on assisted ventilation |  | At 36 weeks post-conceptional age | 
| Length of hospitalization |  | At hospital discharge | 
| Retinopathy of prematurity |  | At hospital discharge | 
| Air leaks |  | At 36 weeks post-conceptual age | 
| Days on oxygen |  | At 36 weeks post-conceptual age | 
| Supplemental oxygen |  | At 36 weeks post-conceptual age | 
| Neurodevelopmental outcome |  | 18-22 months corrected age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Very Low Birth Weight (VLBW), Prematurity, Inhaled nitric oxide, Aspiration syndrome, Idiopathic pulmonary hypertension, Pulmonary hypoplasia