Inhaled Nitric Oxide Treatment of Early Pulmonary Hypertension to Reduce the Risk of Death or Bronchopulmonary Dysplasia in Infants Born Extremely Preterm: A Masked Randomized Controlled Trial.

Abstract

To determine whether inhaled nitric oxide (iNO) treatment of early pulmonary hypertension (PH) would decrease the risk of death or bronchopulmonary dysplasia (BPD) among infants born extremely preterm. This was a single-center, masked, randomized controlled trial involving infants born at ≤29 weeks' gestation and requiring positive pressure ventilation. Exclusion criteria included infants of COVID-19 positive mothers, large patent ductus arteriosus with left to right shunting, left ventricle dysfunction (ejection fraction <40%), significant congenital anomalies/genetic disorders, or iNO treatment by clinicians prior to the study echocardiogram. Initial echocardiogram was performed at 72 ± 24 hours of life to randomize infants with early PH into 2 study arms (iNO vs placebo). Serial echocardiograms were performed every 24-48 hours, up to 14 days of life. Treatment was weaned until PH resolved (responders) or if no improvement was documented ≥72-hours (nonresponders). Primary outcome was death or BPD at 36-weeks postmenstrual age. From July 2019 to October 2023, 683 eligible infants were admitted. We excluded 88 infants; 413 mothers declined consent or were not approached. iNO treatment was clinically started for 51 infants due to hypoxic respiratory failure. Screening echocardiograms were completed for 180 infants; of these, 32 infants with early PH were randomized to iNO or placebo groups. After a planned interim analysis, termination of the trial was recommended by the Data Safety Monitoring Committee because of futility. iNO treatment does not reduce the risk of BPD or death among extremely preterm infants with echocardiographic evidence of early pulmonary hypertension without hypoxic respiratory failure.