• Death
• Chronic Lung Disease at 36 weeks

This multicenter trial tests whether inhaled nitric oxide will reduce death or the need for oxygen in preterm infants (less than 34 weeks gestational age) with severe lung disease.

This multicenter, randomized, double-masked, controlled clinical trial evaluates the efficacy of inhaled nitric oxide (iNO) in the treatment of the preterm infant with respiratory failure secondary to respiratory distress syndrome (RDS), sepsis/pneumonia, aspiration syndrome, idiopathic pulmonary hypertension and/or suspected pulmonary hypoplasia. Infants are followed until death or discharge to home. The trial compares iNO therapy to mock gas delivery as the control and otherwise incorporates conventional management strategies (including treatment with surfactant and high frequency ventilation as adjuncts to iNO therapy). During the initial dosing, iNO is started at 5 ppm and may be increased to 10 ppm. If the infant does not respond, study gas is discontinued. For infants who respond to study gas, a gradual weaning is initiated following a well-defined protocol. The total exposure to study gas may not exceed 336 hours (14 days). Infants are monitored for signs of toxicity. Medical and neurodevelopmental outcome of surviving infants will be assessed at 18 to 22 months corrected age by masked, certified examiners.

To demonstrate that the use of iNO is associated with a clinically significant reduction (from 75% to 60%) in the primary outcome variable (incidence of death or BPD during initial hospitalization) using a power of 0.90 and an alpha of 0.05 for a two-tailed test, a sample of 440 will be required (220 infants in each arm of the study).

• Respiratory Distress Syndrome
• Infant, Premature
• Sepsis
• Pneumonia
• Hypertension, Pulmonary

• Van Meurs KP, Wright LL, Ehrenkranz RA, Lemons JA, Ball MB, Poole WK, Perritt R, Higgins RD, Oh W, Hudak ML, Laptook AR, Shankaran S, Finer NN, Carlo WA, Kennedy KA, Fridriksson JH, Steinhorn RH, Sokol GM, Konduri GG, Aschner JL, Stoll BJ, D'Angio CT, Stevenson DK; Preemie Inhaled Nitric Oxide Study. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med. 2005 Jul 7;353(1):13-22.
• [No authors listed] Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. The Neonatal Inhaled Nitric Oxide Study Group. N Engl J Med. 1997 Feb 27;336(9):597-604.
• Abman SH, Kinsella JP, Schaffer MS, Wilkening RB. Inhaled nitric oxide in the management of a premature newborn with severe respiratory distress and pulmonary hypertension. Pediatrics. 1993 Oct;92(4):606-9. No abstract available.
• Kinsella JP, Walsh WF, Bose CL, Gerstmann DR, Labella JJ, Sardesai S, Walsh-Sukys MC, McCaffrey MJ, Cornfield DN, Bhutani VK, Cutter GR, Baier M, Abman SH. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial. Lancet. 1999 Sep 25;354(9184):1061-5.
• [No authors listed] Early compared with delayed inhaled nitric oxide in moderately hypoxaemic neonates with respiratory failure: a randomised controlled trial. The Franco-Belgium Collaborative NO Trial Group. Lancet. 1999 Sep 25;354(9184):1066-71.

Inclusion Criteria

• Any infant with a birth weight 401 - 1500 grams and < 34 weeks gestational age with an OI (mean Paw x FiO2 x 100/PaO2) > 10 on two consecutive blood gases at least 30 minutes apart, but no more than 12 hours apart.

or

• Infants > 1500 grams and < 34 weeks gestational age will be entered in the Larger Preemie Pilot Study if they have an OI greater than or equal to 15 on two consecutive blood gases at least 30 minutes apart, but no more than 12 hours apart.
• Infants requiring assisted ventilation with a diagnosis of RDS/HMD, pneumonia and/or sepsis, aspiration syndrome, idiopathic pulmonary hypertension, or suspected pulmonary hypoplasia associated with PROM and/or oligohydramnios.
• Greater than or equal to 4 hours after one dose of surfactant.
• Less than or equal to 120 hours of age.
• All infants must have an indwelling arterial line.

Exclusion Criteria

• Any infant in whom a decision has been made not to provide full treatment (e.g. chromosomal anomalies or severe birth asphyxia).
• Known structural congenital heart disease, except patent ductus arteriosus and atrial-level shunts.
• Infants with any major abnormality involving the respiratory system such as congenital diaphragmatic hernia, tracheoesophageal fistula or cystic fibrosis.
• Any bleeding diathesis considered to be clinically significant or thrombocytopenia with platelet count < 50,000.
• Prior enrollment into a conflicting clinical trial such as the Neonatal Network Surfactant CPAP trial.Inclusion Criteria