Safety and Efficacy Study of Nitric Oxide for Inhalation on Chronic Lung Disease in Premature Babies

• Survival Without Bronchopulmonary Dysplasia (BPD) in Preterm Infants With Respiratory Distress [ Time Frame: 36 weeks gestational age ] [ Designated as safety issue: No ]
  The primary outcome was determined by assessment of survival and incidence of BPD,which was defined by the need for supplemental oxygen at 36 weeks gestational age (GA); an infant who was alive without BPD at 36 weeks GA was counted as success; an infant who died or had BPD at 36 weeks GA was counted as a failure.
• Survival [ Time Frame: 36 Weeks GA ] [ Designated as safety issue: No ]

• Vital Signs [ Time Frame: Study Duration ] [ Designated as safety issue: Yes ]
• Arterial Oxygen Saturation by Pulse Oximetry [ Time Frame: Study Duration ] [ Designated as safety issue: Yes ]
• Adverse Events [ Time Frame: Study Duration ] [ Designated as safety issue: Yes ]
• Methemoglobin Level [ Time Frame: Baseline, then 24 hours, 2-6 days, Day 7 and Day 14 of treatment ] [ Designated as safety issue: Yes ]

The purpose of this study is to assess the safety and efficacy of inhaled nitric oxide to reduce the risk of chronic lung disease in pre-term infants with respiratory distress, and to assess the long-term effects of the therapy on the development of these children over 7 years of clinical follow-up.

Although the effects of inhaled Nitric Oxide on pulmonary vascular tone are well-described and relevant to term infants with persistent pulmonary hypertension, the pathophysiology of respiratory failure in preterm infants may be quite different. Chronic lung disease (CLD) represents the final pathway of a heterogeneous group of pulmonary disorders of infancy that usually start in the neonatal period. CLD most commonly occurs in preterm (<30 weeks of gestational age (GA) infants with birth weights less than 1,500 g, and especially in those very preterm (<26 wks GA) with birth weights less than 1,000 g, and who have been treated for respiratory distress syndrome (RDS).

• Drug: Nitric Oxide for inhalation
  inhaled nitric oxide given at 5 parts per million (ppm) for 7-21 days
  Other Name: INOmax®
• Drug: Nitrogen
  nitrogen gas given at 5ppm for 7-21 days

• Group A
  24+0-25+6 days weeks gestational age
  Interventions:

  • Drug: Nitric Oxide for inhalation
  • Drug: Nitrogen
• Group B
  26+0 - 28+6 days weeks Gestational Age
  Interventions:

  • Drug: Nitric Oxide for inhalation
  • Drug: Nitrogen

Inclusion Criteria:

• Inborn preterm infants 24+0 weeks-28+6 days weeks gestational age (defined by first trimester ultrasound or if not available based on the last menstrual period) who requires the use of surfactant within 24 hours of birth (either prophylactically, or for signs of developing respiratory distress), or who requires the use of continuous positive airway pressure (CPAP) (fraction of inspired oxygen concentration (FiO2) ≥ 0.30 on a mean airway pressure ≥ 4cm water (H2O)) within 24 hours of birth in order to maintain an oxygen saturation (SpO2) ≥ 85%.
• Informed consent of the guardian.

Exclusion Criteria:

• Outborn infants.
• Infants ≥ 29 weeks gestational age.
• Infants requiring FiO2 >0.5 to maintain SpO2 >85%, on a sufficient mean airway pressure (e.g., > 8 cm H2O on controlled mechanical ventilation (CMV)) in order to achieve adequate chest inflation (8-9 ribs on Chest X-ray) two hours after the proper administration of exogenous surfactant.
• Any suspected congenital heart disease other than patent ductus arteriosus or atrial septal defect.
• Any infant with severe bleeding or coagulation abnormalities at high-risk of diathesis, e.g., platelet <50,000/mm³, fibrinogen <0.5 g/L, other clotting factors <10%.
• Any infant in whom a decision has been made not to provide full treatment, e.g., chromosomal abnormalities, severe multiple abnormalities, severe birth asphyxia, etc.
• Use of another investigational drug or device before or during the active study period.