Efficacy and Safety of Inhaled Budesonide in Very Preterm Infants at Risk for Bronchopulmonary Dysplasia

Survival of extremely low birth weight (ELBW) infants has improved in recent
decades, however BPD remains a major health care problem. BPD is a chronic lung
disease that occurs in premature infants. BPD not only contributes to the
mortality of preterm infants but is also associated with impaired psychomotor
outcome in ELBW survivors. A number of approaches followed in preventing or
treating BPD have been evaluated in the context of controlled studies. Among
the interventions studied are antenatal and postnatal corticosteroids Systemic
postnatal corticosteroid treatment is perhaps the most controversial approach
known in BPD care. Several reports on the adverse effects of dexamethasone on
growth and neurodevelopmental outcomes appeared, thus the widespread use of
systemic postnatal steroids was replaced by almost complete avoidance of this
form of therapy.
Nevertheless, the incidence of ELBW survivors with BPD is increasing and new
modalities for prevention and treatment need to be explored. Inhaled
corticosteroids have been established as the first-line of treatment in adults
and children with persistent asthma, the most common chronic inflammatory
disease. As in asthma, the biological rationale of corticosteroid therapy in
infants with evolving or established BPD is based on its anti-inflammatory
properties. Some trials concerning inhaled corticosteroids did not prevent BPD,
but was associated with a lower use of systemic glucocorticoid therapy and
mechanical ventilation. One study with Inhaled steroids resulted in a
significantly higher success rate in extubation within the first 2 weeks of
life and a more pronounced improvement in lung compliance.
A study to evaluate the efficacy of inhaled corticosteroids seems to be
justified. The hypothesis of this study is that early prophylactic inhalation
of budesonide reduces the absolute risk of BPD or death in preterm infants born
<28 weeks gestational age by 10%.

Primary objective
- Survival without BPD at 36 weeks gestational age (GA)

Secondary objectives
- Neurodevelopment at a corrected age of 18-22 months
- Adverse treatment effects
- Mortality at 36 weeks gestational age
- BPD incidence at 36 weeks gestational age
- Duration of positive pressure respiratory support or supplemental oxygen

Randomised placebo-controlled, multicentre clinical trial.

Within 2 years 850 infants of 23-27 weeks GA will be randomised during the
first 12 hours of life to Budesonide (BS) of placebo to prevent BPD. Study
drugs will be administered via Aerochamber and continued until infants are
either off supplementary oxygen and poitive pressure support of have reached a
GA of 32 O/7 weeks regardless of ventilatory status.

Inflammation is central to the development of BPD. Corticosteroids (CS) have
antiinflammatory properties and early inhalation of CS may allow for beneficial
local effects on the pulmonary system with a lower risk of undesirable systemic
side effects.