Inhaled Budesonide for Non-ventilated Infants at High Risk of Bronchopulmonary Dysplasia: the i-BUD Pilot Study
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Inhaled budesonide Inhaled budesonide 1mg/dose (2ml) three tid |
Drug: Inhaled budesonide
Inhaled budesonide 1 mg tid until 36 weeks' corrected gestational age or fully weaned from supplemental oxygen and respiratory support (CPAP or high flow nasal canula)
Other Names:
|
| Placebo Comparator: Normal saline Normal saline inhalation 2ml tid |
Drug: Normal saline
2 ml normal saline by inhalation
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Total days on supplemental oxygen from birth to discharge [Participants will be followed for the duration of hospital stay, an expected average of 8 weeks]
Secondary Outcome Measures
- Bronchopulmonary dysplasia [At 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]
- Death or bronchopulmonary dysplasia [Participants will be followed for the duration of hospital stay, an expected average of 8 weeks]
- Days on supplement oxygen after the study enrollment [Participants 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).
- Days with significant apneas [Participants 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
- Culture proven sepsis [Participants will be followed for the duration of hospital stay, an expected average of 8 weeks]
- Gastrointestinal bleeding [Participants will be followed for the duration of hospital stay, an expected average of 8 weeks]
- Persistent hyperglycemia [Participants 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
- Hypertension [Participants 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
- Salivary cortisol level [2 weeks after the study entry and at the first follow up visit at 6 week's corrected age]
- Postnatal growth [at 36 weeks corrected gestational age and at first follow-up visit at 6 weeks' corrected age]
Weight, Head Circumference and Length
- Patent ductus arteriosus [Participants will be followed for the duration of hospital stay, an expected average of 8 weeks]
PDA diagnosed clinically or by echocardiography
Other Outcome Measures
- Intraventricular hemorrhage [Participants will be followed for the duration of hospital stay, an expected average of 8 weeks]
Any grade of intraventricular hemorrhage as assessed on cranial ultrasound
- Periventricular leukomalacia [Participants will be followed for the duration of hospital stay, an expected average of 8 weeks]
Cystic periventricular leukomalacia as assessed by cranial ultrasound
- Retinopathy of prematurity [Participants will be followed for the duration of hospital stay, an expected average of 8 weeks]
Stage 3 or 4 or surgery as determined from ophthalmological examination
- Necrotizing enterocolitis [Participants will be followed for the duration of hospital stay, an expected average of 8 weeks]
Bell's stage 2 or higher
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sunnybrook Health Sciences Centre | Toronto | Ontario | Canada | M4N 3M5 |
Sponsors and Collaborators
- Dr. Michael Dunn
Investigators
- Principal Investigator: Michael Dunn, M.D., Staff Neonatologist
- Principal Investigator: Tetsuya Isayama, M.D., Clinical Fellow
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 001-2013
- CTRL # 165648