Inhaled Nitric Oxide and Neuroprotection in Premature Infants

Study Overview
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Brief Summary
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The purpose of this study is to determine whether inhaled nitric oxide improves the neurological outcome for premature infants.

Detailed Description
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With the advances in modern neonatal intensive care medicine in the last 20 years, survival of extremely preterm infants weighing less than 1500g (< 3 lbs, 5 oz) has risen markedly. However, with this increased survival has come a marked increase in the number of infants with serious neurodevelopmental disabilities: Premature infants with birth weights less than 1500g who survive to go home are at significant risk for serious neurodevelopmental problems: cognitive and motor delays, blindness, deafness, and cerebral palsy. In a recent randomized, placebo-controlled clinical trial, we assessed whether giving mechanically ventilated preterm infants inhaled nitric oxide gas (iNO) for 1 week after birth decreased the incidence of death and chronic lung disease. An unanticipated outcome of that study (Schreiber et. al. 2003) and a subsequent study of those infants at 2 years of age (Mestan et. al. 2005) was that premature infants treated with inhaled nitric oxide (iNO) have improved neurodevelopmental outcomes and physical growth at 2 years corrected age, compared with placebo-treated infants (Mestan et. al. 2005). INO therapy, therefore, appears to be a new treatment to protect the premature brain during development outside the womb. The overall goal of this application is understand the efficacy of iNO treatment in improving neurodevelopmental outcomes in at-risk premature infants.

Official Title
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Inhaled Nitric Oxide and Neuroprotection in Premature Infants

Conditions
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Prematurity, Bronchopulmonary Dysplasia, Intraventricular Hemorrhage, Periventricular Leukomalacia

Intervention / Treatment
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* Drug: inhaled nitric oxide
* Drug: oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prematurity (birthweight ≤ 1500g, < 31 weeks gestation) Requiring respiratory support Admitted to the NICU at the University of Chicago Exclusion Criteria: Severe congenital anomalies Genetic syndromes Extremely sick preterm infants requiring very high ventilatory pressures (OI ≥ 20) Premature infants judged by the physician as nonviable

Ages Eligible for Study
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Minimum Age: 2 Hours
Maximum Age: 72 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INO Treatment<br>The treatment group will receive iNO, combined with O2 or room air, until 33 weeks corrected age. | Drug: inhaled nitric oxide<br>* The amount of gas will be carefully controlled and adjusted to the level that best improves the function of subject's lungs. The subject will remain on inhaled nitric oxide until he/she reaches 33 weeks of gestation if assigned to the treatment arm, or until the 8th day of the study if he/she is assigned to the control arm.<br>* Other names: INO;|
| Placebo Comparator: INO Control<br>INO will be given to infants in the control group for the first 7 days of the study gas, then O2 or room air, as clinically appropriate, on the 8th day, until 33 weeks corrected age | Drug: inhaled nitric oxide<br>* The amount of gas will be carefully controlled and adjusted to the level that best improves the function of subject's lungs. The subject will remain on inhaled nitric oxide until he/she reaches 33 weeks of gestation if assigned to the treatment arm, or until the 8th day of the study if he/she is assigned to the control arm.<br>* Other names: INO;Drug: oxygen<br>* The amount of gas will be carefully controlled and adjusted to the level that best improves the function of the subject's lungs. Subjects in the control arm of the study will receive oxygen beginning on the 8th day of the study until he/she reaches 33 weeks of gestation.<br>* Other names: O2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurodevelopment |  | Two years | 
| Bronchopulmonary dysplasia |  | 36 weeks of age corrected | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe IVH / PVL |  | 40 weeks of age corrected | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prematurity, nitric oxide, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, neurodevelopment