Clinical trial NCT01035190: Efficacy and Safety of Inhaled Budesonide in Very Preterm Infants at Risk for Bronchopulmonary Dysplasia
Official title: Efficacy and Safety of Inhaled Budesonide in Very Preterm Infants at Risk for Bronchopulmonary Dysplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bronchopulmonary Dysplasia
Keywords: Preterm Infants
Inhaled Corticosteroids
Bronchopulmonary Dysplasia
Lead sponsor: University Children's Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: European Union
First posted: 2009-12-18
Enrollment: 863
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Survival without BPD at 36 weeks GA
timeFrame: 36 weeks GA
Secondary outcomes:
measure: Neurodevelopment at a corrected age of 18 - 22 months.
timeFrame: 18 - 22 months
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge Oostende AV, Department of Neontalogy
city: Brussels
country: Belgium
facility: CHU St-Pierre, UMC St-Pieter
city: Bruxelles
country: Belgium
facility: HUDERF, Department of Neonatology
city: La Louvière
country: Belgium
facility: CHU Tivoli, Department of Neonatology
city: Brno
country: Czech Republic
facility: University Hospital Brno, Department of Neonatology
city: Ostrava
country: Czech Republic
facility: University Hospital Ostrava, Department of Neonatology
city: Plzen
country: Czech Republic
facility: University Hospital Plzen, Department of Neonatology
city: Prague 2
country: Czech Republic
facility: Charles University, General Faculty Hospital and 1st Faculty of Medicine, Department of Obstetrics and Gynecology
city: Prague 5
country: Czech Republic
facility: University Hospital Motol Prague 5, Department of Neonatology
city: Zlin
country: Czech Republic
facility: University Hospital of Tomas Bati, Department of Neonatology
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital,Hospital for Children and Adolescents, NICU
city: Kuopio
country: Finland
facility: University Hospital Kuopio, NICU
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospita, NICU
city: Tartu
country: Finland
facility: Tartu University Children's Clinic, Paediatric Intensive Care Unit
city: Lille
country: France
facility: CHU de LilleHôpital Jeanne de Flandres, Pôle de Médecine néonataleUnité de Réanimation néonatale
city: Paris
country: France
facility: Hospital Cochin Saint-Vincent de Paul, Dept. of Neonatology
city: Tours
country: France
facility: Hôpital Clocheville, Service de RéanimationNéonatale
city: Aachen
country: Germany
facility: University Children's Hospital Aachen, Dept. of Neonatology
city: Dresden
country: Germany
facility: University Children's Hospital Carl Gustav Carus Dresden, Dept. of Neonatology
city: Erlangen
country: Germany
facility: University Children's Hospital Erlangen, Dept. of Neonatology
city: Essen
country: Germany
facility: University Children's Hospital Essen, Dept. of Pediatrics
city: Goettingen
country: Germany
facility: Georg-August University Hospital Goettingen, Dept. of Pediatrics
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf, Dept. of Neonatology
city: Hannover
country: Germany
facility: Children's Hospital Hannover auf der Bult, Dept. of Neonatology
city: Hannover
country: Germany
facility: University Hospital Hannover, Dept. of Neonatology
city: Heidelberg
country: Germany
facility: University Children's Hospital Heidelberg, Dept. of Neonatology
city: Nuernberg
country: Germany
facility: Hospital Nuernberg Sued, Dept. of Neonatology
city: Tuebingen
country: Germany
facility: University Children´s Hospital Tuebingen, Dept. of Neonatology
city: Beer Sheva
country: Israel
facility: Ben-Gurion University of NegevSoroka Medical Center, Neonatal Department
city: Haifa
country: Israel
facility: Bnai Zion Medical Center Haifa, Department of Neonatology
city: Jerusalem
country: Israel
facility: Hadassah Medical Center, Department of Neonatology
city: Kfar-Saba
country: Israel
facility: Meir Medical Center, Premature Baby Unit
city: Rehovot
country: Israel
facility: Kaplan Medical Center Rehovot, Dept. of Neonatology
city: Ancona
country: Italy
facility: Ospedale Salesi, SOD Neonatologia
city: Cuneo
country: Italy
facility: ASO S. Croce e Carie, Terapia Intensiva Neonatale-Neonatologia
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova, Dipartimento di Pediatria Salus Pueri
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana, U.O. Neonatologia
city: Torino
country: Italy
facility: Ospedale Sant'Anna, Terapia Intensiva Neonatale Clinica -3°piano
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia, Department of Neonatology
Study officials:
affiliation: University Children's Hospital Tuebingen / University Hospital Zurich, Department of Neonatology
name: Prof. Dr. med. Dirk Bassler, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital, Tuebingen
name: Prof. Dr. med. Christian F Poets
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. No abstract available.
citation: Bassler D, Shinwell ES, Hallman M, Jarreau PH, Plavka R, Carnielli V, Meisner C, Engel C, Koch A, Kreutzer K, van den Anker JN, Schwab M, Halliday HL, Poets CF; Neonatal European Study of Inhaled Steroids Trial Group. Long-Term Effects of Inhaled Budesonide for Bronchopulmonary Dysplasia. N Engl J Med. 2018 Jan 11;378(2):148-157. doi: 10.1056/NEJMoa1708831.
citation: Bassler D, Plavka R, Shinwell ES, Hallman M, Jarreau PH, Carnielli V, Van den Anker JN, Meisner C, Engel C, Schwab M, Halliday HL, Poets CF; NEUROSIS Trial Group. Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia. N Engl J Med. 2015 Oct 15;373(16):1497-506. doi: 10.1056/NEJMoa1501917.