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

Eberhard Karls University of Tübingen

Status and phase

Completed

Phase 3

Conditions

Bronchopulmonary Dysplasia

Treatments

Drug: Budesonide

Study type

Interventional

Funder types

Other

Identifiers

NCT01035190

GAH-F5_2009-223060

Details and patient eligibility

About

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.

Enrollment

863 patients

Sex

All

Ages

Under 12 hours old

Volunteers

No Healthy Volunteers

Inclusion criteria

a gestational age of 23 0/7-27 6/7 weeks,
a postnatal age < 12 hours
the necessity for any form of positive pressure support (mechanical or nasal ventilation or CPAP

Exclusion criteria

involve a clinical decision not to administer therapies (infant not considered viable)
dysmorphic features or congenital malformations that adversely affect life expectancy or neurodevelopment and known or suspected congenital heart disease