Inhaled Nitric Oxide (INO) for the Prevention of Bronchopulmonary Dysplasia (BPD) in Preterm Infants

Study Overview
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Brief Summary
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This phase 3, multi-center, double blind, placebo-controlled, randomized clinical trial will attempt to demonstrate if preterm infants who require mechanical ventilation and/or positive pressure support at any point during days 5 to 14 after birth may benefit from treatment with iNO.

Detailed Description
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Multi-center, double blind, placebo-controlled, randomized clinical trial. Infants who meet all enrollment criteria at any point during days 5 to 14 after birth will be randomized to inhaled NO starting at 20 ppm, or matching placebo, by means of a blinded INOvent® delivery device. All infants will receive 24 days of therapy, following a dose reduction schedule. Infants who are extubated before 24 days will continue therapy via nasal continuous positive airway pressure (CPAP) or nasal cannula to complete 24 days' of therapy. The primary outcome measure will be survival without BPD at 36 weeks gestational age using a physiologic assessment of BPD.

Official Title
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Inhaled Nitric Oxide (INO) for the Prevention of Bronchopulmonary Dysplasia (BPD) in Preterm Infants Requiring Mechanical Ventilation or Positive Pressure Support on Days 5-14 After Birth

Conditions
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Bronchopulmonary Dysplasia

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: Preterm infants who are: 500 to 1250 grams at birth < 30 weeks gestational age 5 to 14 days of age (inclusive) at the time of entry Requiring mechanical ventilation or for those infants ≤ 800 grams, positive pressure support (including CPAP) for respiratory insufficiency on days 5 to 14 days of age (inclusive) Exclusion Criteria: Preterm infants with life-threatening anomalies (cranial, cardiac, thoracic, chromosomal) or congenital diaphragmatic hernia with lung hypoplasia, or any subject who will not receive complete intensive care Preterm infants with bilateral Grade 4 intraventricular hemorrhage (IVH) Subjects who are dependent on right to left shunting to maintain the systemic circulation Preterm infants who received prior iNO therapy Use of another investigational agent

Ages Eligible for Study
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Minimum Age: 5 Days
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: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled Nitric Oxide<br>Inhaled Nitric Oxide | Drug: Inhaled Nitric Oxide<br>* Inhaled Nitric Oxide will be administered continuously starting at 20ppm into the inspiratory limb of the ventilator circuit in mechanically ventilated subject using an INOvent delivery system of by nasal cannula as needed for 24 days of therapy.<br>* Other names: INOmax;|
| Placebo Comparator: Placebo<br>Nitrogen Placebo | Drug: Placebo<br>* Nitrogen gas will be administered in the same manner as the experimental drug.<br>* Other names: Nitrogen gas;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival Without BPD at 36 Weeks |  | Baseline, 36 weeks PMA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days of Airway Pressure Support - Intent-to-treat Population | Airway pressure support includes conventional mechanical ventilation, conventional, high frequency oscillatory ventilation, jet, continuous positive airway pressure, and other. | Through hospital discharge, an average of 105 days for placebo and 108 days for INO | 
| Length of Birth Hospitalization |  | Through hospital discharge, an average of 105 days for placebo and 108 days for INO | 
| Number and Percentage of Participants With Use of Postnatal Corticosteroids for Bronchopulmonary Dysplasia |  | Through hospital discharge, an average of 105 days for placebo and 108 days for INO | 
| Number and Percentage of Participants With Use of Postnatal Corticosteroids for Any Medical Reason |  | Through hospital discharge, an average of 105 days for placebo and 108 days for INO | 
| Systemic Use of Postnatal Corticosteroids for Any Medical Reason |  | Through hospital discharge, an average of 105 days for placebo and 108 days for INO | 
| Number of Days of Oxygen Use |  | Through hospital discharge, an average of 105 days for placebo and 108 days for INO | 
| Severity of Bronchopulmonary Dysplasia | Severity of bronchopulmonary dysplasia defined by the fraction of inspired O2 concentration (FiO2) requirement. | 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchopulmonary Dysplasia, BPD