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Inhaled nitric oxide (NO) therapy does not appear to achieve reduction in the incidence of bronchopulmonary dysplasia in preterm infants, according to data published online Sept. 25 in JAMA Pediatrics.
Shabih U. Hasan, MD, from the Cumming School of Medicine at the University of Calgary, and his coauthors wrote that inhaled nitric oxide is currently approved for the treatment of hypoxic respiratory failure in infants with pulmonary hypertension. Animal studies have prompted interest in its potential to prevent bronchopulmonary dysplasia in preterm infants, but randomized trials so far have shown mixed results (JAMA Pediatr. 2017 Sep 25. doi: 10.1001/jamapediatrics.2017.2618).
The dosage selected was higher, and the treatment was given for a longer period and initiated later than in some previous studies, which the authors hypothesized might improve outcomes.
However, there was no significant difference between the placebo and inhaled NO groups in the primary outcome of survival to 36 weeks postmenstrual age without bronchopulmonary dysplasia (31.5% vs. 34.9%).
Similarly, the rate of severe bronchopulmonary dysplasia was similar for placebo and inhaled nitric oxide (26.6% vs. 20.5%), as was the rate of postnatal corticosteroid use (41.0% vs. 41.5%), mean days of positive pressure respiratory support (55 vs. 54), mean days of oxygen therapy (88 vs. 91) and mean days of hospitalization (105 vs. 108).
The subgroup analysis revealed that characteristics such as birth weight, gestational age, sex, postnatal age at study entry, maternal race or mode of respiratory support also did not influence the outcomes.
While the rates of severe bronchopulmonary dysplasia were similar between the placebo and inhaled nitric oxide groups, the inhaled NO group had a larger number of infants whose mothers were white and a higher rate of rupture of membranes for more than 7 days, compared with the placebo group.
The two groups had similar incidence of prematurity complications, such as sepsis, patent ductus arteriosus, necrotizing enterocolitis, retinopathy, intraventricular hemorrhage, and pulmonary air leak.
There were also no significant differences in neurodevelopmental or respiratory outcomes at 18-24 months postmenstrual age.
The authors commented that they had hoped their results would be similar to the earlier NO CLD trial, which hinted at a substantial increase in survival without bronchopulmonary dysplasia, compared with placebo in infants aged 7-14 days at the start of treatment.
“The NO CLD trial was not powered to assess the primary outcome in the subgroup enrolled between ages 7 and 14 days, whereas our study was powered specifically for that purpose and included twice as many infants in each treatment arm,” the authors wrote.
Despite this, and a lack of any obvious differences between the study populations, the authors could not identify a reason for the lack of efficacy seen in their own study, compared with this earlier study.
The authors noted that their findings of a lack of benefit from prophylactic but delayed NO on bronchopulmonary dysplasia were consistent with previous meta-analyses, and with a consensus statement from the National Institutes of Health.
The study was sponsored by Mallinckrodt Pharmaceuticals. Four authors declared honorarium, speaking engagements, advisory positions or consultancies with Mallinckrodt Pharmaceuticals. No other conflicts of interest were declared.
Inhaled nitric oxide (NO) therapy does not appear to achieve reduction in the incidence of bronchopulmonary dysplasia in preterm infants, according to data published online Sept. 25 in JAMA Pediatrics.
Shabih U. Hasan, MD, from the Cumming School of Medicine at the University of Calgary, and his coauthors wrote that inhaled nitric oxide is currently approved for the treatment of hypoxic respiratory failure in infants with pulmonary hypertension. Animal studies have prompted interest in its potential to prevent bronchopulmonary dysplasia in preterm infants, but randomized trials so far have shown mixed results (JAMA Pediatr. 2017 Sep 25. doi: 10.1001/jamapediatrics.2017.2618).
The dosage selected was higher, and the treatment was given for a longer period and initiated later than in some previous studies, which the authors hypothesized might improve outcomes.
However, there was no significant difference between the placebo and inhaled NO groups in the primary outcome of survival to 36 weeks postmenstrual age without bronchopulmonary dysplasia (31.5% vs. 34.9%).
Similarly, the rate of severe bronchopulmonary dysplasia was similar for placebo and inhaled nitric oxide (26.6% vs. 20.5%), as was the rate of postnatal corticosteroid use (41.0% vs. 41.5%), mean days of positive pressure respiratory support (55 vs. 54), mean days of oxygen therapy (88 vs. 91) and mean days of hospitalization (105 vs. 108).
The subgroup analysis revealed that characteristics such as birth weight, gestational age, sex, postnatal age at study entry, maternal race or mode of respiratory support also did not influence the outcomes.
While the rates of severe bronchopulmonary dysplasia were similar between the placebo and inhaled nitric oxide groups, the inhaled NO group had a larger number of infants whose mothers were white and a higher rate of rupture of membranes for more than 7 days, compared with the placebo group.
The two groups had similar incidence of prematurity complications, such as sepsis, patent ductus arteriosus, necrotizing enterocolitis, retinopathy, intraventricular hemorrhage, and pulmonary air leak.
There were also no significant differences in neurodevelopmental or respiratory outcomes at 18-24 months postmenstrual age.
The authors commented that they had hoped their results would be similar to the earlier NO CLD trial, which hinted at a substantial increase in survival without bronchopulmonary dysplasia, compared with placebo in infants aged 7-14 days at the start of treatment.
“The NO CLD trial was not powered to assess the primary outcome in the subgroup enrolled between ages 7 and 14 days, whereas our study was powered specifically for that purpose and included twice as many infants in each treatment arm,” the authors wrote.
Despite this, and a lack of any obvious differences between the study populations, the authors could not identify a reason for the lack of efficacy seen in their own study, compared with this earlier study.
The authors noted that their findings of a lack of benefit from prophylactic but delayed NO on bronchopulmonary dysplasia were consistent with previous meta-analyses, and with a consensus statement from the National Institutes of Health.
The study was sponsored by Mallinckrodt Pharmaceuticals. Four authors declared honorarium, speaking engagements, advisory positions or consultancies with Mallinckrodt Pharmaceuticals. No other conflicts of interest were declared.
Inhaled nitric oxide (NO) therapy does not appear to achieve reduction in the incidence of bronchopulmonary dysplasia in preterm infants, according to data published online Sept. 25 in JAMA Pediatrics.
Shabih U. Hasan, MD, from the Cumming School of Medicine at the University of Calgary, and his coauthors wrote that inhaled nitric oxide is currently approved for the treatment of hypoxic respiratory failure in infants with pulmonary hypertension. Animal studies have prompted interest in its potential to prevent bronchopulmonary dysplasia in preterm infants, but randomized trials so far have shown mixed results (JAMA Pediatr. 2017 Sep 25. doi: 10.1001/jamapediatrics.2017.2618).
The dosage selected was higher, and the treatment was given for a longer period and initiated later than in some previous studies, which the authors hypothesized might improve outcomes.
However, there was no significant difference between the placebo and inhaled NO groups in the primary outcome of survival to 36 weeks postmenstrual age without bronchopulmonary dysplasia (31.5% vs. 34.9%).
Similarly, the rate of severe bronchopulmonary dysplasia was similar for placebo and inhaled nitric oxide (26.6% vs. 20.5%), as was the rate of postnatal corticosteroid use (41.0% vs. 41.5%), mean days of positive pressure respiratory support (55 vs. 54), mean days of oxygen therapy (88 vs. 91) and mean days of hospitalization (105 vs. 108).
The subgroup analysis revealed that characteristics such as birth weight, gestational age, sex, postnatal age at study entry, maternal race or mode of respiratory support also did not influence the outcomes.
While the rates of severe bronchopulmonary dysplasia were similar between the placebo and inhaled nitric oxide groups, the inhaled NO group had a larger number of infants whose mothers were white and a higher rate of rupture of membranes for more than 7 days, compared with the placebo group.
The two groups had similar incidence of prematurity complications, such as sepsis, patent ductus arteriosus, necrotizing enterocolitis, retinopathy, intraventricular hemorrhage, and pulmonary air leak.
There were also no significant differences in neurodevelopmental or respiratory outcomes at 18-24 months postmenstrual age.
The authors commented that they had hoped their results would be similar to the earlier NO CLD trial, which hinted at a substantial increase in survival without bronchopulmonary dysplasia, compared with placebo in infants aged 7-14 days at the start of treatment.
“The NO CLD trial was not powered to assess the primary outcome in the subgroup enrolled between ages 7 and 14 days, whereas our study was powered specifically for that purpose and included twice as many infants in each treatment arm,” the authors wrote.
Despite this, and a lack of any obvious differences between the study populations, the authors could not identify a reason for the lack of efficacy seen in their own study, compared with this earlier study.
The authors noted that their findings of a lack of benefit from prophylactic but delayed NO on bronchopulmonary dysplasia were consistent with previous meta-analyses, and with a consensus statement from the National Institutes of Health.
The study was sponsored by Mallinckrodt Pharmaceuticals. Four authors declared honorarium, speaking engagements, advisory positions or consultancies with Mallinckrodt Pharmaceuticals. No other conflicts of interest were declared.
FROM JAMA PEDIATRICS
Key clinical point: Treatment with inhaled nitric oxide does not reduce the incidence of bronchopulmonary dysplasia in preterm infants.
Major finding: The incidence of bronchopulmonary dysplasia in preterm infants was not reduced with inhaled nitric oxide therapy.
Data source: Prospective randomized placebo-controlled trial in 451 preterm infants of less than 30 weeks gestation.
Disclosures: The study was sponsored by Mallinckrodt Pharmaceuticals. Four authors declared honorarium, speakers fees, advisory positions, or consultancies with Mallinckrodt Pharmaceuticals. No other conflicts of interest were declared.