Study of Inhaled Nitric Oxide (iNO) and Respiratory Outcomes in Late Preterm Infants

Phase 2

Terminated

Interventions: Drug: inhaled nitric oxide
Drug: Placebo Comparator - nitrogen gas

Brief Summary: The aim of this study is to determine if inhaled nitric oxide will improve short and long term respiratory outcomes in preterm infants. Infants born at a gestational age of 30-36 weeks and who require breathing support with high flow nasal cannula, nasal continuous positive airway pressure, or nasal intermittent positive pressure will be randomized to receive either inhaled nitric oxide or placebo. The dose will then be decreased per protocol until all respiratory support has been discontinued. Infants will be followed to evaluate safety and efficacy of non-invasive iNO delivery, up to 12 months corrected gestational age.

Recruitment & Eligibility

Inclusion Criteria

<48 hours of age,
30 - 36 weeks gestational age at birth based on best estimate using obstetrical sonography (first or second trimester), solid dating criteria, or Ballard examination,
Birth weight of ≥ 1,000 g,
5 minute Apgar score ≥5,
Requiring nasal cannula O2 > 1 liter per minute (LPM), continuous positive pressure (CPAP), or non invasive positive pressure ventilation (NIPPV) for treatment of respiratory failure,
Requiring a fraction of inspired oxygen (FIO2) of at least 0.25 to maintain arterial oxygen saturation (SaO2) 88-94%,
Parent or guardian has signed informed consent and agrees to all study- related procedures, including those required after hospital discharge.

Exclusion Criteria

Major congenital anomaly
Intubation and surfactant in the delivery room or prior to enrollment in the Neonatal Intensive Care Unit (NICU). Excludes intubation for suctioning.
Known congenital infection (bacterial, viral),
Perinatal asphyxia (5 minute Apgar <5, umbilical artery pH < 7.0 or evidence of neonatal encephalopathy),
Mother and/or infant is enrolled in another clinical trial (excluding observational) or has received an investigational drug,
Has undergone or is anticipated to require a major surgical procedure within the first 48 h of life,
Any condition which could preclude receiving study drug or performing any study-related procedures,
Use of postnatal corticosteroids,
Parent or guardian is unable or unwilling to complete study procedures after hospital discharge.

Arm && Interventions

Group	Intervention	Description
inhaled Nitric Oxide	inhaled nitric oxide	iNO to start at 20 parts per million (ppm) for the first three days of life. The dose will then be decreased to 10 ppm for three days, 5 ppm for 3 days and then 2 ppm until all high flow respiratory support has been discontinued.
Nitrogen Gas	Placebo Comparator - nitrogen gas	Placebo gas will be adjusted the same as study gas: to start at 20ppm for the first three days of life. The dose will then be decreased to 10 ppm for three days, 5 ppm for 3 days and then 2 ppm until all high flow respiratory support has been discontinued.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Were Alive Without the Need for Intubation or Mechanical Ventilation Within the First Week of Life	7 days

Secondary Outcome Measures

Name	Time	Method
Total Duration of Respiratory Support	From hospital admission through discharge	participants were followed for the duration of hospital stay for respiratory support
Total Length of Hospital Stay	From hospital admission through discharge	participants who were followed for the duration of hospital stay
Number of Participants Who Had the Need for Exogenous Surfactant	7 days
Evidence of Chronic Respiratory Morbidity at 12 Months Corrected Gestational Age (CGA)	12 months corrected gestational age	defined by a validated system of parental diaries and pulmonary questionnaires, as well as review of medical records (medical visits, respiratory medication use, emergency room visits, and hospital re-admissions)
Total Duration of Supplemental Oxygen	From Hospital Admission through discharge	Participants were followed for the duration of hospital stay for use of supplemental oxygen
Diagnosis of Bronchopulmonary Dysplasia (BPD)	At 36 weeks postmenstrual age or 1-2month of age	Diagnosis of BPD by oxygen challenge test at 36 weeks post menstrual age (PMA) for infants born between 30 and 32 weeks gestational age (GA). For those born 32 1/7 - 36 weeks, an oxygen challenge test was performed at 1-2 months of age.