Inhaled Corticosteroids for Treatment of Bronchopulmonary Dysplasia
Status:
Completed
Trial end date:
2006-11-15
Target enrollment:
Participant gender:
Summary
While many short-term morbidities associated with extreme prematurity have declined over the
last two decades, the incidence of bronchopulmonary dysplasia (BPD) has increased to a rate
of approximately 45% in neonates <28 weeks gestational age (GA) and birth weight (BW) <1,500
g. Neonates with BPD are at increased risk for adverse short-and long-term neurodevelopmental
and respiratory outcomes that often persist into adulthood.
There is a growing body of pathological and biochemical evidence that implicates inflammation
in its pathogenesis. This is further supported by randomized controlled trials (RCTs) that
demonstrate the efficacy of systemic corticosteroids in facilitating extubation and reducing
BPD. However, several short- and long-term adverse effects associated with the use of
systemic corticosteroids have been described, the most concerning of which is their effect on
neurodevelopment, specifically an increased rate of cerebral palsy (CP).
Inhaled corticosteroids (ICS) are an attractive alternative to systemic steroids because of
these concerns. Earlier systematic reviews had not found any benefit in using ICS for the
prevention or treatment of BPD. However, a recent systematic review showed a significant
reduction in death or BPD at 36 weeks' corrected GA (CGA) (risk ratio=0.86, 95% confidence
interval 0.75, 0.99), BPD (RR=0.77, 95% CI 0.65, 0.91), and use of systemic steroids
(RR=0.87, 95% CI 0.76, 0.98) in infants treated with ICS.
Despite growing evidence of the effectiveness of ICS for BPD, uncertainty remains over
treatment timing, effective dose, and long-term effects. There is also variation in the
delivery systems used for delivery of ICS. These concerns continue to be echoed in a recent
review by Nelin et al. Given that the long-term neurodevelopmental impact of ICS were unknown
at the time of this study and many infants are able to wean from ventilation without
steroids, the investigators conducted an escalating-dose ranging study of late ICS (i.e.
administered after the first week of life) delivered by a metered dose inhaler (MDI)
utilizing a specially designed valved delivery system to determine the minimum effective dose
necessary to achieve extubation or reduction in oxygen requirements and the long-term
neurodevelopmental impact of increasing doses of ICS.
Phase:
N/A
Details
Lead Sponsor:
Mount Sinai Hospital, Canada
Collaborators:
IWK Health Centre Sunnybrook Health Sciences Centre