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

Bronchopulmonary Dysplasia Clinical Trial

— NEuroSIS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01035190
• Other study ID #: GAH-F5_2009-223060
• Status: Completed
• Phase: Phase 3
• First received: December 17, 2009
• Last updated: July 4, 2016
• Start date: April 2010
• Est. completion date: July 2016

Study information

• Verified date: July 2016
• Source: University Children’s Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesCzech Republic: State Institute for Drug ControlFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Israel: Israeli Health Ministry Pharmaceutical AdministrationItaly: The Italian Medicines AgencyNetherlands: Medicines Evaluation Board (MEB)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 863
• Est. completion date: July 2016
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 12 Hours

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Hyperplasia

Intervention

Drug:
• Budesonide
Inhalation, 200 µg/puff

Locations

Country	Name	City	State
Belgium	AZ Sint-Jan Brugge Oostende AV, Department of Neontalogy	Brugge
Belgium	CHU St-Pierre, UMC St-Pieter	Brussels
Belgium	HUDERF, Department of Neonatology	Bruxelles
Belgium	CHU Tivoli, Department of Neonatology	La Louvière
Czech Republic	University Hospital Brno, Department of Neonatology	Brno
Czech Republic	University Hospital Ostrava, Department of Neonatology	Ostrava
Czech Republic	University Hospital Plzen, Department of Neonatology	Plzen
Czech Republic	Charles University, General Faculty Hospital and 1st Faculty of Medicine, Department of Obstetrics and Gynecology	Prague 2
Czech Republic	University Hospital Motol Prague 5, Department of Neonatology	Prague 5
Czech Republic	University Hospital of Tomas Bati, Department of Neonatology	Zlin
Finland	Helsinki University Central Hospital,Hospital for Children and Adolescents, NICU	Helsinki
Finland	University Hospital Kuopio, NICU	Kuopio
Finland	Oulu University Hospital	Oulu
Finland	Tampere University Hospita, NICU	Tampere
Finland	Tartu University Children's Clinic, Paediatric Intensive Care Unit	Tartu
France	CHU de LilleHôpital Jeanne de Flandres, Pôle de Médecine néonataleUnité de Réanimation néonatale	Lille
France	Hospital Cochin Saint-Vincent de Paul, Dept. of Neonatology	Paris
France	Hôpital Clocheville, Service de RéanimationNéonatale	Tours
Germany	University Children's Hospital Aachen, Dept. of Neonatology	Aachen
Germany	University Children's Hospital Carl Gustav Carus Dresden, Dept. of Neonatology	Dresden
Germany	University Children`s Hospital Erlangen, Dept. of Neonatology	Erlangen
Germany	University Children`s Hospital Essen, Dept. of Pediatrics	Essen
Germany	Georg-August University Hospital Goettingen, Dept. of Pediatrics	Goettingen
Germany	University Hospital Hamburg-Eppendorf, Dept. of Neonatology	Hamburg
Germany	Children`s Hospital Hannover auf der Bult, Dept. of Neonatology	Hannover
Germany	University Hospital Hannover, Dept. of Neonatology	Hannover
Germany	University Children`s Hospital Heidelberg, Dept. of Neonatology	Heidelberg
Germany	Hospital Nuernberg Sued, Dept. of Neonatology	Nuernberg
Germany	University Children´s Hospital Tuebingen, Dept. of Neonatology	Tuebingen
Israel	Ben-Gurion University of NegevSoroka Medical Center, Neonatal Department	Beer Sheva
Israel	Bnai Zion Medical Center Haifa, Department of Neonatology	Haifa
Israel	Hadassah Medical Center, Department of Neonatology	Jerusalem
Israel	Meir Medical Center, Premature Baby Unit	Kfar-Saba
Israel	Kaplan Medical Center Rehovot, Dept. of Neonatology	Rehovot
Italy	Ospedale Salesi, SOD Neonatologia	Ancona
Italy	ASO S. Croce e Carie, Terapia Intensiva Neonatale-Neonatologia	Cuneo
Italy	Azienda Ospedaliera di Padova, Dipartimento di Pediatria Salus Pueri	Padova
Italy	Azienda Ospedaliera Universitaria Pisana, U.O. Neonatologia	Pisa
Italy	Ospedale Sant'Anna, Terapia Intensiva Neonatale Clinica -3°piano	Torino
Netherlands	Erasmus MC - Sophia, Department of Neonatology	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
University Children’s Hospital Tuebingen	European Union

Countries where clinical trial is conducted

Belgium,  Czech Republic,  Finland,  France,  Germany,  Israel,  Italy,  Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival without BPD at 36 weeks GA		36 weeks GA	No
Secondary	Neurodevelopment at a corrected age of 18 - 22 months.		18 - 22 months	Yes