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

Mallinckrodt

Status and phase: Completed; Phase 3

Conditions: Lung Disease

Treatments: Drug: Placebo; Drug: Nitric oxide

Study type: Interventional

Funder types: Industry

Identifiers

NCT00551642

2004-002312-29 (EudraCT Number)

INOT27

Details and patient eligibility

About

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.

Full description

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 grams (g), and especially in those very preterm (<26 weeks GA) with birth weights less than 1,000 g, and who have been treated for respiratory distress syndrome (RDS).

Enrollment: 800 patients

Sex: All

Ages: Under 26 hours old

Volunteers: No Healthy Volunteers

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 per millimeter cube (mm³), fibrinogen <0.5 gram per liter (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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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800 participants in 2 patient groups, including a placebo group

Inhaled Nitric Oxide (INO)

Active Comparator group

Description:

INO administered by nasal continuous positive airway pressure, nasal cannula or face mask at 5 parts per million (ppm) for between 7 and 21 days

Treatment:

Drug: Nitric oxide

Placebo

Placebo Comparator group

Description:

Placebo gas administered by nasal continuous positive airway pressure, nasal cannula or face mask, for a maximum of 21 days.

Treatment:

Drug: Placebo