Inhaled Nitric Oxide by Oxygen Hood in Neonates

Study Overview
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Brief Summary
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Inhaled nitric oxide (iNO) improves oxygenation in term infants with respiratory failure. However, iNO has been primarily used in infants receiving mechanical ventilation. This study is a pilot study to determine if iNO given into an oxygen hood is effective in improving oxygenation in term and near-term infants who have poor oxygenation but who are not yet mechanically ventilated.

Detailed Description
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Inhaled nitric oxide (iNO) is currently used in the management of ventilated neonates with hypoxemic respiratory failure. We have shown that iNO administered by oxygen hood reduces pulmonary vascular resistance in hypoxia- and group B streptococcus-induced pulmonary hypertension in an animal model (J Perinatol 2002; 22:50-6). Our objective was to determine the feasibility of iNO administration by oxygen hood in neonates with respiratory failure. Methods: A masked randomized controlled trial was performed on eight infants with respiratory failure. Inclusion criteria were: gestation>34 weeks, age<7 days, with post-ductal arterial line, and A-aDO2 400-600 on two consecutive blood gases. Infants were randomized to study gas (iNO at 20 ppm or equivalent flow of O2) for 1 hr which was then weaned over the next 4 hours. The iNO was introduced into an oxygen hood using an INOvent (INO Therapeutics, Inc). The primary outcome was the PaO2 one hour after randomization. Environmental leakage of NO and NO2 were measured. Results: Four infants were randomized to iNO and four to O2 (controls). Two of the four infants given iNO had an increase in PaO2 of >100 mm Hg, while oxygenation was unchanged in the controls. Methemoglobinemia and other adverse effects were not noted in any infant. Environmental levels of NO and NO2 were minimal (<1ppm) to undetectable at >0.3m from the hood. Conclusions: Administration of iNO by oxygen hood is feasible. Larger randomized controlled trials are required to measure the efficacy and determine an appropriate target population for this technique.

Official Title
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Inhaled Nitric Oxide in Neonates With Elevated A-aDO2 Gradients Not Requiring Mechanical Ventilation

Conditions
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Respiratory Failure, Infant, Persistent Fetal Circulation

Intervention / Treatment
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* Drug: inhaled Nitric Oxide
* Drug: Oxygen (>90% by hood) - standard therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: gestation >34 weeks at birth age <7 days post-ductal arterial line an A-aDO2 of 400 to 600 on two blood gases, at least 30 minutes apart. Exclusion Criteria: Infants with major malformations Infants with cardiac disease

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 1 Week

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled Nitric Oxide<br>iNO started at 20 ppm for 1 hour. The gas was then weaned hourly over the next 4 hours (20 ppm to 10 to 5 to 2.5 to 1 to off). | Drug: inhaled Nitric Oxide<br>* iNO started at 20 ppm for 1 hour, then weaned hourly over the next 4 hours (20 ppm to 10 to 5 to 2.5 to 1 to off). If >5% drop in oxygen saturation was observed during weaning, study gas was increased to the previous concentration and weaning done 2 hourly. If > 5% drop in oxygen saturation or >5% Methemoglobin was observed during initial administration, the study gas would be weaned over 30 minutes and the infant would exit. The iNO was introduced into an oxygen hood (Oxydome ™ disposable hood from Maxtex ® Inc.) using an INOvent (Datex-Ohmeda). The INOvent ® was connected to the oxyhood by placing the injector module inline on the dry side of the humidifier chamber. Monitoring of O2, NO2, NO was done by placing the end of the sample line inside the oxyhood. A Masking Shield covered the Display/Control Panel and Cylinder Gauges, in order to maintain masking of the intervention. Only the respiratory therapist and research coordinator was aware of the allocation assignment.<br>* Other names: Nitric Oxide;|
| Placebo Comparator: Placebo<br>The Oxygen at high concentration (>90%), which was standard therapy for PPHN, was introduced into an oxygen hood (Oxydome ™ disposable hood from Maxtex ® Inc.) using an INOvent (Datex-Ohmeda). | Drug: Oxygen (>90% by hood) - standard therapy<br>* Oxygen (>90% by hood, standard therapy for PPHN prior to intubation) was introduced into an oxygen hood (Oxydome ™ disposable hood from Maxtex ® Inc.) using an INOvent (Datex-Ohmeda). The INOvent ® was connected to the oxyhood by placing the injector module inline on the dry side of the humidifier chamber. If the baby was randomized to the control group and did not receive NO, the INOmax® cylinder was opened and used only to pressurize the system, which prevented the Low NO Pressure alarm. A Masking Shield covered the Display/Control Panel and Cylinder Gauges, in order to maintain masking of the intervention. Only the respiratory therapist and research coordinator was aware of the allocation assignment.<br>* Other names: Head box;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PaO2 one hour after the first hour of study gas |  | one hour after the first hour of study gas | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alveolar-arterial oxygen gradient (A-a DO2) |  | one hour of exposure to treatment gas | 
| oxygen saturation by pulse oximetry (SpO2) |  | continuously through the study | 
| need for mechanical ventilation |  | Continuously through the study | 
| duration of oxygen therapy |  | continuously through the study | 
| Methemoglobin level in post-ductal arterial blood (MetHb) |  | Hourly until completion of study in infant | 
| Platelet count |  | As needed if bleeding | 
| Systemic blood pressure |  | hourly | 
| Environmental NO and NO2 exposure |  | Hourly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoxia, Respiratory failure, Infant, term, Nitric oxide