Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants

Study Overview
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Brief Summary
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To determine whether or not inhaled nitric oxide (iNO) safely decreases the incidence of chronic lung disease (CLD) in premature infants.

Detailed Description
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BACKGROUND: Despite advances in medical, nursing, and respiratory care, CLD affects up to 50 percent of premature infants. As a result, nearly 50,000 infants in the United States develop CLD. It is desirable to investigate therapies that decrease the incidence of CLD because it is associated with failure to thrive, developmental delay, increased risk of pulmonary infection, reactive airway disease, pulmonary hypertension, and death. DESIGN NARRATIVE: This is a randomized, double-blind, placebo-controlled, multi-center study. Three specific hypotheses will be tested: 1) iNO reduces the incidence of CLD; 2) iNO reduces serum and lung (tracheal aspirate) markers of inflammation; and 3) iNO does not increase the incidence of intraventricular hemorrhage in premature neonates. The primary endpoint is survival without CLD (defined as continued oxygen requirement) at 36 weeks post conceptional age. A total of 793 premature newborns will be enrolled from 14 centers within 48 hours of birth. They will be randomly assigned to receive either placebo or iNO at 5 ppm until the breathing tube can be safely removed or after 21 days. The iNO will be delivered by an INOvent delivery system in such a way that physicians and nurses will not know which treatment each participant is receiving. Management strategies for aspects of patient care including mechanical ventilation, surfactant administration, fluid administration, and steroid use will be determined by physicians at each center. Serial cranial ultrasounds and methemoglobin levels will be monitored to determine adverse events. The first 200 patients will have serial blood samples and tracheal aspirates obtained for measurements of inflammatory mediators, including interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), endothelin-1, myeloperoxidase, neutrophil counts (tracheal aspirates), and endothelin-1 (blood). Participants will be seen at 12 and 24 months of age to monitor the long-term effects on the cardiopulmonary or neurologic systems. At these visits, a health questionnaire will be administered and Bayley II scales of infant development will be completed.

Official Title
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Inhaled NO for the Prevention of Chronic Lung Disease

Conditions
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Lung Diseases, Bronchopulmonary Dysplasia

Intervention / Treatment
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* Drug: iNO
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Weighing between 500 to 1250 grams at birth Gestational age of less than 34 weeks Less than 48 hours old Respiratory failure on mechanical ventilation Absence of structural heart disease (PDA, ASD less than 1 cm, or VSD less than 2 mm are permitted if known prior to study entry) Absence of lethal congenital anomaly Exclusion Criteria: Concurrent participation in another experimental study (observational studies will be allowed with prior approval by the Steering Committee and Data and Safety Monitoring Board) Active pulmonary hemorrhage Unevaluated pneumothorax High frequency jet ventilation Expected short duration of ventilation (less than 48 hours from birth)

Ages Eligible for Study
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Maximum Age: 1 Year

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled Nitric Oxide (iNO)<br>Nitric Oxide study gas will be initiated at 5 ppm using the INOvent delivery system. The delivery system provides for masked delivery of the treatment gas. This dose will be used for a 21-day period or until extubation. | Drug: iNO<br>* Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants<br>* Other names: Inhaled nitric oxide.;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Inhaled Nitrogen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant's survival without CLD |  | (measured at 36 weeks after birth) |