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

NCT ID: NCT01035190

Last Updated: 2016-07-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

863 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-04-30

Study Completion Date

2016-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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Bronchopulmonary Dysplasia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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inhaled Budesonide

Group Type EXPERIMENTAL

Budesonide

Intervention Type DRUG

Inhalation, 200 µg/puff

Interventions

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Budesonide

Inhalation, 200 µg/puff

Intervention Type DRUG

Other Intervention Names

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Budiair

Eligibility Criteria

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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
Maximum Eligible Age

12 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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European Union

OTHER

Sponsor Role collaborator

University Children's Hospital Tuebingen

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. med. Dirk Bassler, Msc

Prof.Dr. med.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Prof. Dr. med. Dirk Bassler, MSc

Role: PRINCIPAL_INVESTIGATOR

University Children's Hospital Tuebingen / University Hospital Zurich, Department of Neonatology

Prof. Dr. med. Christian F Poets

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital, Tuebingen

Locations

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AZ Sint-Jan Brugge Oostende AV, Department of Neontalogy

Bruges, , Belgium

Site Status

CHU St-Pierre, UMC St-Pieter

Brussels, , Belgium

Site Status

HUDERF, Department of Neonatology

Brussels, , Belgium

Site Status

CHU Tivoli, Department of Neonatology

La Louvière, , Belgium

Site Status

University Hospital Brno, Department of Neonatology

Brno, , Czechia

Site Status

University Hospital Ostrava, Department of Neonatology

Ostrava, , Czechia

Site Status

University Hospital Plzen, Department of Neonatology

Pilsen, , Czechia

Site Status

Charles University, General Faculty Hospital and 1st Faculty of Medicine, Department of Obstetrics and Gynecology

Prague, , Czechia

Site Status

University Hospital Motol Prague 5, Department of Neonatology

Prague, , Czechia

Site Status

University Hospital of Tomas Bati, Department of Neonatology

Zlín, , Czechia

Site Status

Helsinki University Central Hospital,Hospital for Children and Adolescents, NICU

Helsinki, , Finland

Site Status

University Hospital Kuopio, NICU

Kuopio, , Finland

Site Status

Oulu University Hospital

Oulu, , Finland

Site Status

Tampere University Hospita, NICU

Tampere, , Finland

Site Status

Tartu University Children's Clinic, Paediatric Intensive Care Unit

Tartu, , Finland

Site Status

CHU de LilleHôpital Jeanne de Flandres, Pôle de Médecine néonataleUnité de Réanimation néonatale

Lille, , France

Site Status

Hospital Cochin Saint-Vincent de Paul, Dept. of Neonatology

Paris, , France

Site Status

Hôpital Clocheville, Service de RéanimationNéonatale

Tours, , France

Site Status

University Children's Hospital Aachen, Dept. of Neonatology

Aachen, , Germany

Site Status

University Children's Hospital Carl Gustav Carus Dresden, Dept. of Neonatology

Dresden, , Germany

Site Status

University Children's Hospital Erlangen, Dept. of Neonatology

Erlangen, , Germany

Site Status

University Children's Hospital Essen, Dept. of Pediatrics

Essen, , Germany

Site Status

Georg-August University Hospital Goettingen, Dept. of Pediatrics

Göttingen, , Germany

Site Status

University Hospital Hamburg-Eppendorf, Dept. of Neonatology

Hamburg, , Germany

Site Status

Children's Hospital Hannover auf der Bult, Dept. of Neonatology

Hanover, , Germany

Site Status

University Hospital Hannover, Dept. of Neonatology

Hanover, , Germany

Site Status

University Children's Hospital Heidelberg, Dept. of Neonatology

Heidelberg, , Germany

Site Status

Hospital Nuernberg Sued, Dept. of Neonatology

Nuremberg, , Germany

Site Status

University Children´s Hospital Tuebingen, Dept. of Neonatology

Tübingen, , Germany

Site Status

Ben-Gurion University of NegevSoroka Medical Center, Neonatal Department

Beersheba, , Israel

Site Status

Bnai Zion Medical Center Haifa, Department of Neonatology

Haifa, , Israel

Site Status

Hadassah Medical Center, Department of Neonatology

Jerusalem, , Israel

Site Status

Meir Medical Center, Premature Baby Unit

Kfar Saba, , Israel

Site Status

Kaplan Medical Center Rehovot, Dept. of Neonatology

Rehovot, , Israel

Site Status

Ospedale Salesi, SOD Neonatologia

Ancona, , Italy

Site Status

ASO S. Croce e Carie, Terapia Intensiva Neonatale-Neonatologia

Cuneo, , Italy

Site Status

Azienda Ospedaliera di Padova, Dipartimento di Pediatria Salus Pueri

Padua, , Italy

Site Status

Azienda Ospedaliera Universitaria Pisana, U.O. Neonatologia

Pisa, , Italy

Site Status

Ospedale Sant'Anna, Terapia Intensiva Neonatale Clinica -3°piano

Torino, , Italy

Site Status

Erasmus MC - Sophia, Department of Neonatology

Rotterdam, , Netherlands

Site Status

Countries

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Belgium Czechia Finland France Germany Israel Italy Netherlands

References

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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.

Reference Type BACKGROUND
PMID: 19590247 (View on PubMed)

Ciora OA, Seegmuller T, Fischer JS, Wirth T, Hafner F, Stoecklein S, Flemmer AW, Forster K, Kindt A, Bassler D, Poets CF, Ahmidi N, Hilgendorff A. Delineating morbidity patterns in preterm infants at near-term age using a data-driven approach. BMC Pediatr. 2024 Apr 11;24(1):249. doi: 10.1186/s12887-024-04702-5.

Reference Type DERIVED
PMID: 38605404 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29320647 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26465983 (View on PubMed)

Other Identifiers

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GAH-F5_2009-223060

Identifier Type: -

Identifier Source: org_study_id

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