Clinical trial NCT01895075: Inhaled Budesonide for Non-ventilated Infants at High Risk of Bronchopulmonary Dysplasia: the i-BUD Pilot Study
Official title: Evaluation of the Effectiveness of Inhaled Budesonide for Non-ventilated Infants at High Risk of Bronchopulmonary Dysplasia: the i-BUD Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Bronchopulmonary Dysplasia
Keywords: Budesonide
Inhalation
Premature infants
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
First posted: 2013-07-10
Enrollment: 0
Sex: ALL
Minimum age (years): 14
Maximum age (years): 42
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Bronchopulmonary dysplasia (BPD) is one of the most important morbidities of preterm infants with a high incidence and significant impact on resource utilization and long-term outcome. Systemic corticosteroids have been shown to be effective in the prevention of BPD through their potent anti-inflammatory effects but there are serious concerns on their potential detrimental effects on neurodevelopment of infants. In contrast, inhaled corticosteroids administered to ventilated infants are thought to be safer due to their topical effect but have not been shown to improve outcomes including BPD. To date, there have been few studies evaluating the effect of inhaled corticosteroids administered to non-ventilated infants for the prevention of BPD. Hence, we are conducting a double-blind randomized controlled pilot trial to examine the impact of inhaled budesonide on non-ventilated infants.

The study objectives, in a cohort of very preterm infants with signs of early BPD are: 1) to evaluate the effect of aerosolized budesonide on 'days on supplemental oxygen', and 2) to gain an estimate of the impact on BPD and 3) to assess the safety of the intervention in a small cohort of preterm infants.

This will be a single-center randomized double-blind controlled pilot trial. We will recruit a total of 50 infants born at less than 30 weeks gestation who are on continuous positive airway pressure (CPAP) with fraction of inspired oxygen ≥25% on day 14 of life or later. Inhaled budesonide 1mg (intervention group) or normal saline (placebo) will be administered three times a day until the infants do not need CPAP or supplemental oxygen or reach 36+0/7 weeks corrected gestational age. We will evaluate 'days on supplemental oxygen', BPD, re-intubation rates, days on mechanical ventilation and days on CPAP as well as adverse outcomes.

The prevention of BPD would have a significant positive impact on patient quality of life and medical resource utilization and costs. The study hypothesis is that inhaled budesonide on non-ventilated infants with early signs of BPD will reduce the 'days on supplemental oxygen' indicating a positive effect for the prevention of BPD. The result of this pilot study might also justify and support to proceed to a large confirmatory study to evaluate an effect of the intervention on BPD, in which the estimate of the impact on BPD gained in this pilot trial may be used to calculate a sample size.


Eligibility criteria: Inclusion Criteria:

* Spontaneous breathing preterm Infants on day 14 to day 42 of age
* Born at \< 30 0/7 weeks gestational age
* Requiring FiO2 ≥ 25% on CPAP including biphasic CPAP or high flow nasal canula

Exclusion Criteria:

* Presence of chromosomal defects or major congenital anomalies
* Presence of severe infections including sepsis, meningitis, pneumonia, systemic fungal infections
* History of administration of systemic corticosteroids for pulmonary problems, not including that for hypotension

Primary outcomes:
measure: Total days on supplemental oxygen from birth to discharge
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Secondary outcomes:
measure: Bronchopulmonary dysplasia
timeFrame: At 36+0/7 weeks corrected gestational age
measure: Mortality (all causes)
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Death or bronchopulmonary dysplasia
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Days on supplement oxygen after the study enrollment
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Days on continuous positive airway pressure (CPAP)
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Days with significant apneas
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Culture proven sepsis
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Gastrointestinal bleeding
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Persistent hyperglycemia
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Hypertension
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Salivary cortisol level
timeFrame: 2 weeks after the study entry and at the first follow up visit at 6 week's corrected age
measure: Postnatal growth
timeFrame: at 36 weeks corrected gestational age and at first follow-up visit at 6 weeks' corrected age
measure: Patent ductus arteriosus
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Other outcomes:
measure: Intraventricular hemorrhage
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Periventricular leukomalacia
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Retinopathy of prematurity
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: Necrotizing enterocolitis
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Staff Neonatologist
name: Michael Dunn, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Fellow
name: Tetsuya Isayama, M.D.
role: PRINCIPAL_INVESTIGATOR
References: