Inhaled Nitric Oxide and Neuroprotection in Premature Infants

Phase 2

Terminated

Conditions: Periventricular Leukomalacia
Prematurity
Bronchopulmonary Dysplasia
Intraventricular Hemorrhage

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

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
INO Control (Short iNO)	inhaled nitric oxide	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
INO Treatment (Long iNO)	inhaled nitric oxide	The treatment group will receive iNO, combined with O2 or room air, until 33 weeks corrected age.
INO Treatment (Long iNO)	oxygen	The treatment group will receive iNO, combined with O2 or room air, until 33 weeks corrected age.

Primary Outcome Measures

Name	Time	Method
Neurodevelopment	Two years
Bronchopulmonary Dysplasia (BPD) or Death	36 weeks of age corrected (BPD) or before discharge (death)	Need for respiratory support at 36 weeks post-menstrual age, either as positive pressure or supplemental oxygen to maintain oxygen saturations \>90%, or death before discharge

Secondary Outcome Measures

Name	Time	Method
Death	through discharge (up to 400 days)	Death before discharge
Bronchopulmonary Dysplasia	36 weeks of age corrected	Need for respiratory support at 36 weeks post-menstrual age (PMA), either as positive pressure or supplemental oxygen to maintain oxygen saturations \>90%
Supplemental Oxygen Use	40 weeks PMA
BPD or Death in Infants Weighing < 750g	36 weeks of age corrected (BPD) or before discharge (death)	Need for respiratory support at 36 weeks post-menstrual age, either as positive pressure or supplemental oxygen to maintain oxygen saturations \>90%, or death before discharge among infants \< 750g
BPD or Death in Infants Weighing 750-999g	36 weeks of age corrected (BPD) or before discharge (death)	Need for respiratory support at 36 weeks post-menstrual age, either as positive pressure or supplemental oxygen to maintain oxygen saturations \>90%, or death before discharge among infants 750-999g
BPD or Death in Black Infants	36 weeks of age corrected (BPD) or before discharge (death)	Need for respiratory support at 36 weeks post-menstrual age, either as positive pressure or supplemental oxygen to maintain oxygen saturations \>90%, or death before discharge among Black infants