Final Report Summary - NEUROSIS (Efficacy and Safety of Inhaled Budesonide in Very Preterm Infants at Risk for Bronchopulmonary Dysplasia)
Executive Summary:
Background and rationale
Bronchopulmonary dysplasia (BPD) contributes to the mortality of preterm infants and is as-sociated with impaired neurosensory development and an increased risk of pulmonary mor-bidity in adolescence and young adulthood. Early systemic corticosteroids reduce the risk of BPD in extremely preterm infants, but they may negatively affect the developing brain. The effects of inhaled corticosteroids on outcomes in these infants are unclear.
Plan at outset
The Neonatal European Study of Inhaled Steroids (NEUROSIS) is a randomized placebo-controlled, international clinical trial. We planned to randomize 850 infants of 23-27 weeks' postmenstrual age during the first 12 h of life to budesonide or placebo. We intended to de-termine the primary outcome of survival without BPD at 36 weeks' postmenstrual age and to follow our study patients and assess neurodevelopmental outcomes at a corrected age of 18-22 months.
Objectives achieved
Between 2010 and 2013, we randomized 863 infants (gestational age of 23 0/7 to 27 6/7 weeks) to early inhaled budesonide or placebo in 40 study centres in 8 European countries and in Israel. The primary outcome was death at 36 weeks or bronchopulmonary dysplasia. Of 437 infants assigned to budesonide, 175 died or had bronchopulmonary dysplasia (40.0%), compared with 194 of 419 assigned to placebo (46.3%) (relative risk, stratified for gestational age, 0.86; 95% CI 0.75-1.00; P=0.05). The rate of bronchopulmonary dysplasia was 27.8% in the budesonide group vs. 38.0% in the placebo group (relative risk, stratified for gestational age, 0.74; 95% CI, 0.60-0.91; P=0.004) and mortality was 16.9% vs. 13.6% respectively (relative risk, stratified for gestational age, 1.24; 95% CI 0.91-1.69; p=0.17). An assessment of neurodevelopmental disability is currently being conducted at 18-22 months corrected age and the results will be available in 2016.
Conclusion
The primary objectives of NEUROSIS were achieved completely. The assessment of the long-term follow-up is ongoing until 2016 and the results will be very important for future guidance.
Background and rationale
Bronchopulmonary dysplasia (BPD) contributes to the mortality of preterm infants and is as-sociated with impaired neurosensory development and an increased risk of pulmonary mor-bidity in adolescence and young adulthood. Early systemic corticosteroids reduce the risk of BPD in extremely preterm infants, but they may negatively affect the developing brain. The effects of inhaled corticosteroids on outcomes in these infants are unclear.
Plan at outset
The Neonatal European Study of Inhaled Steroids (NEUROSIS) is a randomized placebo-controlled, international clinical trial. We planned to randomize 850 infants of 23-27 weeks' postmenstrual age during the first 12 h of life to budesonide or placebo. We intended to de-termine the primary outcome of survival without BPD at 36 weeks' postmenstrual age and to follow our study patients and assess neurodevelopmental outcomes at a corrected age of 18-22 months.
Objectives achieved
Between 2010 and 2013, we randomized 863 infants (gestational age of 23 0/7 to 27 6/7 weeks) to early inhaled budesonide or placebo in 40 study centres in 8 European countries and in Israel. The primary outcome was death at 36 weeks or bronchopulmonary dysplasia. Of 437 infants assigned to budesonide, 175 died or had bronchopulmonary dysplasia (40.0%), compared with 194 of 419 assigned to placebo (46.3%) (relative risk, stratified for gestational age, 0.86; 95% CI 0.75-1.00; P=0.05). The rate of bronchopulmonary dysplasia was 27.8% in the budesonide group vs. 38.0% in the placebo group (relative risk, stratified for gestational age, 0.74; 95% CI, 0.60-0.91; P=0.004) and mortality was 16.9% vs. 13.6% respectively (relative risk, stratified for gestational age, 1.24; 95% CI 0.91-1.69; p=0.17). An assessment of neurodevelopmental disability is currently being conducted at 18-22 months corrected age and the results will be available in 2016.
Conclusion
The primary objectives of NEUROSIS were achieved completely. The assessment of the long-term follow-up is ongoing until 2016 and the results will be very important for future guidance.
