Efficacy and Safety of Inhaled Budesonide in Very Preterm Infants at Risk for Bronchopulmonary Dysplasia
Status:
Completed
Trial end date:
2016-07-01
Target enrollment:
Participant gender:
Summary
HYPOTHESIS:
Early prophylactic inhalation of Budesonide reduces the absolute risk of developing
bronchopulmonary dysplasia (BPD) or death in preterm infants born <28 weeks gestational age
(GA) by 10%.
PRIMARY OBJECTIVE:
To determine whether inhalation of Budesonide within 12 hours of life improves survival
without BPD at 36 weeks GA in infants born between 23 and 27 weeks GA.
SECONDARY OBJECTIVES:
To determine whether prophylactic inhalation of Budesonide affects neurodevelopment at a
corrected age of 18-22 months in preterm infants; to determine whether inhalation of
corticosteroids is associated with adverse treatment effects, alters mortality at 36 weeks
GA, BPD incidence at 36 weeks GA, and the duration of positive pressure respiratory support
or supplemental oxygen.
RATIONALE:
Pre- and postnatal exposure of the developing lung to inflammation is central to the
development of BPD and the pulmonary inflammatory response in preterms at risk of developing
BPD is established very early in life. Corticosteroids have antiinflammatory properties and
early inhalation of corticosteroids may allow for beneficial local effects on the pulmonary
system prior to the development of a full inflammatory response with a lower risk of
undesirable systemic side effects.
STUDY DESIGN:
Randomised placebo-controlled, multi-centre clinical trial.
RESEARCH PLAN:
Within 2 years 850 infants of 23-27 weeks GA will be randomised during the first 12 hours of
life to Budesonide or placebo to prevent BPD. Study drugs will be administered via
Aerochamber and continued until infants are either off supplementary oxygen and positive
pressure support or have reached a GA of 32 0/7 weeks regardless of ventilatory status. The
primary outcome of survival without BPD will be determined at 36 weeks GA and BPD will be
defined according to the physiological definition. Study patients will be followed and
neurodevelopmental outcomes will be assessed at a corrected age of 18-22 months.
CLINICAL SIGNIFICANCE:
BPD not only contributes to the mortality of preterm infants but is also associated with
impaired neurosensory development in Extremely Low Birth Weight (ELBW) survivors, frequent
readmission to hospital in the first 2 years of life, as well as with an increased risk of
asthma, lung function abnormalities and persistent respiratory symptoms in adolescence and
young adulthood. Systemic corticosteroids are effective in preventing BPD, but their use is
practically prohibited given their adverse effects on neurodevelopment. Early inhalation of
corticosteroids has been shown to be associated with secondary pulmonary benefits, but its
effect on survival without BPD and on neurodevelopment remains unclear.
Phase:
Phase 3
Details
Lead Sponsor:
University Children's Hospital Tuebingen University Children’s Hospital Tuebingen