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Inhaled Budesonide for Non-ventilated Infants at High Risk of Bronchopulmonary Dysplasia: the i-BUD Pilot Study

Phase 2
Withdrawn
Conditions
Bronchopulmonary Dysplasia
Interventions
Drug: Normal saline
Registration Number
NCT01895075
Lead Sponsor
Dr. Michael Dunn
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Normal salineNormal salineNormal saline inhalation 2ml tid
Inhaled budesonideInhaled budesonideInhaled budesonide 1mg/dose (2ml) three tid
Primary Outcome Measures
NameTimeMethod
Total days on supplemental oxygen from birth to dischargeParticipants will be followed for the duration of hospital stay, an expected average of 8 weeks
Secondary Outcome Measures
NameTimeMethod
Patent ductus arteriosusParticipants will be followed for the duration of hospital stay, an expected average of 8 weeks

PDA diagnosed clinically or by echocardiography

Culture proven sepsisParticipants will be followed for the duration of hospital stay, an expected average of 8 weeks
Salivary cortisol level2 weeks after the study entry and at the first follow up visit at 6 week's corrected age
Death or bronchopulmonary dysplasiaParticipants will be followed for the duration of hospital stay, an expected average of 8 weeks
Days on supplement oxygen after the study enrollmentParticipants will be followed for the duration of hospital stay, an expected average of 8 weeks
Days on continuous positive airway pressure (CPAP)Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Support with continuous positive airway pressure, including use of biphasic CPAP and high flow nasal canula (\>= 1L/minutes).

Bronchopulmonary dysplasiaAt 36+0/7 weeks corrected gestational age

Bronchopulmonary dysplasia is defined as supplemental oxygen use at 36+0/7 weeks corrected gestational age

Mortality (all causes)Participants will be followed for the duration of hospital stay, an expected average of 8 weeks
Days with significant apneasParticipants will be followed for the duration of hospital stay, an expected average of 8 weeks

Significant apneas with more than 12 episodes requiring stimulation or more than one episode requiring mask-bagging in a six hour period

Gastrointestinal bleedingParticipants will be followed for the duration of hospital stay, an expected average of 8 weeks
Postnatal growthat 36 weeks corrected gestational age and at first follow-up visit at 6 weeks' corrected age

Weight, Head Circumference and Length

Persistent hyperglycemiaParticipants will be followed for the duration of hospital stay, an expected average of 8 weeks

blood glucose \> 10mmol/L more than twice in one day

HypertensionParticipants will be followed for the duration of hospital stay, an expected average of 8 weeks

blood pressure ≥ 95th percentile for infant's gestational and postnatal ages

Trial Locations

Locations (1)

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

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