Inhaled Corticosteroids for Treatment of Bronchopulmonary Dysplasia

NCT03503994 | Completed DMC

• 1 other identifier: 2000/363
• Study Type: interventional
• Target: 41
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Bronchopulmonary Dysplasia

Outcome Measures

Primary Outcomes (2)

• Reduction in FiO2 > 75%

  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% = \[0.21 + 0.25 (0.51-0.21)\]

  1 week per dose

• Successful extubation

  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.

  1 week per dose

Secondary Outcomes (3)

• Ventilator rate (breaths per minute)

  1 week

• Mean airway pressure (cm H2O)

  1 week

• Peak inspiratory pressure (cm H2O)

  1 week

Study Arms (1)

Drug

OTHER

Patients receiving inhaled beclomethasone diproprionate in four escalating doses: 1. 200 mcg bid 2. 400 mcg bid 3. 600 mcg bid 4. 800 mcg bid

Drug: Inhaled Beclomethasone Dipropionate Monohydrate

Interventions

Inhaled Beclomethasone Dipropionate Monohydrate DRUG

Beclomethasone Dipropionate (HFA-BDP, QVAR\*) in the following doses will be evaluated: 1. 200 mcg bid 2. 400 mcg bid 3. 600 mcg bid 4. 800 mcg bid

Drug

Eligibility Criteria

• Age: 1 Week - 4 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Birth weight \< 1,250 grams
• Gestational age \< 32 weeks
• Need for assisted, invasive mechanical ventilation with at least the following settings:
• ventilation rate \> 15 breaths per min, fractional oxygen concentration of inspired gas (FiO2) \> 30% but \< 60%)
• Postnatal age 10-21 days
• Stable ventilatory requirements over the 48-72 hours prior to enrollment

You may not qualify if:

• Actual or suspected sepsis
• Congenital cardiorespiratory malformation
• Patent ductus arteriosus
• Presence of necrotizing enterocolitis
• Presence of gastrointestinal hemorrhage or perforation
• Treatment with systemic dexamethasone

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• Sunnybrook Health Sciences Centre: collaborator
• IWK Health Centre: collaborator

Related Publications (1)

• Raghuram K, Dunn M, Jangaard K, Reilly M, Asztalos E, Kelly E, Vincer M, Shah V. Inhaled corticosteroids in ventilated preterm neonates: a non-randomized dose-ranging study. BMC Pediatr. 2018 May 7;18(1):153. doi: 10.1186/s12887-018-1134-7.

  PMID: 29734948 DERIVED

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Neonatologist

Study Record Dates

• First Submitted: March 30, 2018
• First Posted: April 20, 2018
• Study Start: July 27, 2001
• Primary Completion: November 15, 2006
• Study Completion: November 15, 2006
• Last Updated: April 20, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share