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

Overview

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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 2013

Interventions

  • Drug: Budesonide
    • Inhalation, 200 µg/puff

Arms, Groups and Cohorts

  • Experimental: inhaled Budesonide

Clinical Trial Outcome Measures

Primary Measures

  • Survival without BPD at 36 weeks GA
    • Time Frame: 36 weeks GA

Secondary Measures

  • Neurodevelopment at a corrected age of 18 – 22 months.
    • Time Frame: 18 – 22 months

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: 12 Hours

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Children’s Hospital Tuebingen
  • Collaborator
    • European Union
  • Provider of Information About this Clinical Study
    • Principal Investigator: Prof. Dr. med. Dirk Bassler, Msc, Prof.Dr. med. – University Children’s Hospital Tuebingen
  • Overall Official(s)
    • Prof. Dr. med. Dirk Bassler, MSc, Principal Investigator, University Children’s Hospital Tuebingen / University Hospital Zurich, Department of Neonatology
    • Prof. Dr. med. Christian F Poets, Principal Investigator, Children’s Hospital, Tuebingen

References

Bassler D, Halliday HL, Plavka R, Hallman M, Shinwell ES, Jarreau PH, Carnielli V, van den Anker J, Schwab M, Poets CF. The Neonatal European Study of Inhaled Steroids (NEUROSIS): an eu-funded international randomised controlled trial in preterm infants. Neonatology. 2010;97(1):52-5. doi: 10.1159/000227294. Epub 2009 Jul 7.

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