Inhaled Corticosteroids for Treatment of Bronchopulmonary Dysplasia
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|ClinicalTrials.gov Identifier: NCT03503994|
Recruitment Status : Completed
First Posted : April 20, 2018
Last Update Posted : April 20, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Bronchopulmonary Dysplasia||Drug: Inhaled Beclomethasone Dipropionate Monohydrate||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Dose-Ranging Study to Assess the Effect of Inhaled Corticosteroids in Ventilated Preterm Neonates|
|Actual Study Start Date :||July 27, 2001|
|Actual Primary Completion Date :||November 15, 2006|
|Actual Study Completion Date :||November 15, 2006|
Patients receiving inhaled beclomethasone diproprionate in four escalating doses:
Drug: Inhaled Beclomethasone Dipropionate Monohydrate
Beclomethasone Dipropionate (HFA-BDP, QVAR*) in the following doses will be evaluated:
- Reduction in FiO2 > 75% [ Time Frame: 1 week per dose ]Reduction in FiO2 (%) from the 2 days prior to treatment to the final 2 days of the study period. A reduction in additional FiO2 of 75% or greater will be considered a significant improvement. For example, a baby with a baseline FiO2 of 51% would have a significant reduction in FiO2 if post-treatment FiO2 is less than 0.28 using the following calculation: FiO2 reduction 75% = [0.21 + 0.25 (0.51-0.21)]
- Successful extubation [ Time Frame: 1 week per dose ]Extubation during the study period is considered to be successful if the infant does not require assisted, invasive ventilation for at least 48 hours after the removal of the endotracheal tube and is extubated during the treatment period.
- Ventilator rate (breaths per minute) [ Time Frame: 1 week ]Ventilator rate (breaths per minute) at the end of treatment
- Mean airway pressure (cm H2O) [ Time Frame: 1 week ]The mean airway pressure (cm H2O) required by the baby at the end of treatment
- Peak inspiratory pressure (cm H2O) [ Time Frame: 1 week ]The peak inspiratory pressure (cm H2O) required by the baby at the end of treatment