Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure (Preemie iNO)

NICHD Neonatal Research Network

Status and phase

Terminated

Phase 3

Conditions

Respiratory Distress Syndrome (RDS)

Hypertension, Pulmonary

Infant, Low Birth Weight

Infant, Newborn

Infant, Small for Gestational Age

Pneumonia

Infant, Premature

Sepsis

Treatments

Drug: Placebo

Drug: Inhaled nitric oxide

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00016523

U10HD021373 (U.S. NIH Grant/Contract)

M01RR016587 (U.S. NIH Grant/Contract)

U10HD027853 (U.S. NIH Grant/Contract)

M01RR000032 (U.S. NIH Grant/Contract)

M01RR000044 (U.S. NIH Grant/Contract)

M01RR000070 (U.S. NIH Grant/Contract)

U10HD040521 (U.S. NIH Grant/Contract)

M01RR006022 (U.S. NIH Grant/Contract)

U10HD027880 (U.S. NIH Grant/Contract)

U10HD040498 (U.S. NIH Grant/Contract)

M01RR000633 (U.S. NIH Grant/Contract)

U10HD027856 (U.S. NIH Grant/Contract)

M01RR007122 (U.S. NIH Grant/Contract)

M01RR000750 (U.S. NIH Grant/Contract)

U10HD040689 (U.S. NIH Grant/Contract)

U10HD021397 (U.S. NIH Grant/Contract)

NICHD-NRN-0026

M01RR008084 (U.S. NIH Grant/Contract)

U10HD034216 (U.S. NIH Grant/Contract)

U10HD021385 (U.S. NIH Grant/Contract)

U10HD027904 (U.S. NIH Grant/Contract)

U10HD040461 (U.S. NIH Grant/Contract)

U10HD027871 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full description

This multicenter, randomized, double-masked, controlled clinical trial evaluated 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 were followed until death or discharge to home. The trial compared iNO therapy to mock gas delivery as the control, and otherwise incorporated conventional management strategies (including treatment with surfactant and high frequency ventilation as adjuncts to iNO therapy).

During the initial dosing, iNO was started at 5 ppm and could be increased to 10 ppm. If the infant did not respond, study gas was discontinued. For infants who responded to study gas, a gradual weaning was initiated. The total exposure to study gas did not exceed 336 hours (14 days). Infants were monitored for signs of toxicity.

Medical and neurodevelopmental outcome of surviving infants were assessed at 18 to 22 months corrected age by masked, certified examiners.

Enrollment

420 patients

Sex

All

Ages

Under 120 hours old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.

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