Article Text

  1. J C Mercier1,
  2. H Hummler2,
  3. X Durrmeyer3,
  4. M SanchezLuna4,
  5. V Carnielli5,
  6. D Field6,
  7. B van Overmeire7,
  8. B Jonsson8,
  9. M Hallman9,
  10. J S Baldassarre10
  1. 1Hôpital Robert Debré, Paris, France
  2. 2Division of Neonatalogy, Children’s Hospital, University of Ulm, Ulm, Germany
  3. 3Department of Neonatology, Centre Hospitalier Intercommunal de Créteil, Créteil, France
  4. 4Department of Neonatology, Hospital Universitario Gregorio Marañon, Madrid, Spain
  5. 5Department of Neonatology, Polytechnic University of Marche, Mother and Child Institute Ospedale Salesi, Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona, Ancona, Italy
  6. 6Department of Neonatology, Leicester Royal Infirmary, Leicester, UK
  7. 7Department of Neonatology, Antwerp University Hospital, Antwerpen, Belgium
  8. 8Department of Neonatology, Karolinska Institutet, Stockholm, Sweden
  9. 9Department of Neonatology, University Hospital, Oulu, Finland
  10. 10Department of Clinical Development, Ikaria, Clinton, New Jersey, USA


Introduction Several studies have tested the use of low dose inhaled nitric oxide (iNO) for the prevention of bronchopulmonary dysplasia (BPD) in preterm infants, with inconclusive results. We conducted a randomised controlled trial in nine European countries to test the hypothesis that low dose iNO improves survival without BPD and to examine the effects of iNO on neurodevelopmental outcome.

Methods Infants were enrolled if they were premature, gestational age 24 + 0 to 25 + 6 and 26 + 0 to 28 + 6 weeks, birth weight ⩾500 g and had respiratory distress requiring either surfactant or continuous positive airway pressure (CPAP) greater than 4 cm H2O with FiO2 greater than 0.3 to maintain SpO2 of 85% or greater. Infants were excluded if they required FiO2 greater than 0.5. Infants were randomly assigned to 5 ppm iNO or placebo within 24 h after birth, for 7 days, up to 21 days if they still required respiratory support. Cranial ultrasound was performed at baseline, days 7, 21 and 36 weeks post-conceptual age (PCA). The primary outcome was survival without BPD at 36 weeks PCA. Long-term follow-up is ongoing.

Results 800 infants were randomly assigned at 36 centres in nine EU countries. The median gestational age was 26.6 weeks and median birth weight was 835 g. 90% were intubated at study entry, and 10% were on CPAP. The median OI at study entry was 3.2. The median duration of study therapy was 20.7 days. 34% experienced either death or BPD. Intracranial haemorrhage (all grades) was reported in 16.8% of infants. There were no changes in methaemoglobin.

Conclusions This study is still blinded; results by assigned treatment will be presented.

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