| Methods |
Randomised multi‐centre study, with oxygen used as placebo gas |
| Participants |
235 near‐term infants, ≥ 34 weeks' gestation, OI > 25 on 2 blood gases, 15 minutes apart. Congenital diaphragmatic hernia excluded, congenital heart disease excluded, < 14 days of age only |
| Interventions |
iNO at 20 ppm, trial at 80 ppm if no response to 20 ppm (in treatment group). Comparison with control. Both groups received 'maximal therapy' before study entry, including surfactant in the majority, high‐frequency ventilation at experienced centres, muscle relaxation and inotropes. Induction of alkalosis with target pH of 7.45‐7.60 was also used as a guideline. All of these treatment strategies were continued in controls. Investigators were not allowed to start high‐frequency ventilation or to administer surfactant after study entry. |
| Outcomes |
Survival to 120 days or discharge home, without requiring ECMO. Secondary outcomes were oxygenation (OI and PaO2) after 30 minutes, length of hospital stay, days of assisted ventilation and incidence of air leak or bronchopulmonary dysplasia. Neurodevelopment at 18‐24 months |
| Notes |
|
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Prepared by study centre |
| Allocation concealment (selection bias) |
Low risk |
Telephone randomisation system |
| Blinding (performance bias and detection bias)
All outcomes |
Low risk |
Masked gas administration |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
|
| Selective reporting (reporting bias) |
Low risk |
Study registered, NCT00005776, in 2000 (after completion). Outcomes in registration documents are reported in the main publication. |
| Funding Source(s) |
Unclear risk |
Started with government agency support, industry support after study commenced |
