Bronchopulmonary DysplasiaPhase 3NEuroSISNCT01035190
Efficacy and Safety of Inhaled Budesonide in Very Preterm Infants at Risk for Bronchopulmonary Dysplasia
A Phase 3 study testing Budesonide in people with Bronchopulmonary Dysplasia, run by University Children's Hospital Tuebingen at 40 sites in 8 countries.
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%. Read more about this study
- Who is it for?
- Ages Up to 12 hours
- Conditions the study is for
- Bronchopulmonary Dysplasia
- What is being tested?
- Budesonide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 863 participants
- Where
- 40 sitesin 8 countries
- Study dates
- Apr 2010to Jul 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 12 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
40 sites in 8 countries.
40 sites in 8 countries
Germany11 sites
University Children's Hospital Aachen, Dept. of Neonatology
Aachen, 52074
University Children's Hospital Carl Gustav Carus Dresden, Dept. of Neonatology
Dresden, 01307
University Children's Hospital Erlangen, Dept. of Neonatology
Erlangen, 91054
University Children's Hospital Essen, Dept. of Pediatrics
Essen, 45147
Georg-August University Hospital Goettingen, Dept. of Pediatrics
Göttingen, 37075
University Hospital Hamburg-Eppendorf, Dept. of Neonatology
Hamburg, 20246
Children's Hospital Hannover auf der Bult, Dept. of Neonatology
Hanover, 30173
University Hospital Hannover, Dept. of Neonatology
Hanover, 30625
University Children's Hospital Heidelberg, Dept. of Neonatology
Heidelberg, 69120
Hospital Nuernberg Sued, Dept. of Neonatology
Nuremberg, 90471
University Children´s Hospital Tuebingen, Dept. of Neonatology
Tübingen, 72076
Czechia6 sites
University Hospital Brno, Department of Neonatology
Brno, 62500
University Hospital Ostrava, Department of Neonatology
Ostrava, 70852
University Hospital Plzen, Department of Neonatology
Pilsen, 30599
Charles University, General Faculty Hospital and 1st Faculty of Medicine, Department of Obstetrics and Gynecology
Prague, 12800
University Hospital Motol Prague 5, Department of Neonatology
Prague, 15006
University Hospital of Tomas Bati, Department of Neonatology
Zlín, 76201
Finland5 sites
Helsinki University Central Hospital,Hospital for Children and Adolescents, NICU
Helsinki, 00029
University Hospital Kuopio, NICU
Kuopio, 70211
Oulu University Hospital
Oulu, 90220
Tampere University Hospita, NICU
Tampere, 33521
Tartu University Children's Clinic, Paediatric Intensive Care Unit
Tartu, 50406
Israel5 sites
Ben-Gurion University of NegevSoroka Medical Center, Neonatal Department
Beersheba, 84101
Bnai Zion Medical Center Haifa, Department of Neonatology
Haifa, 31048
Hadassah Medical Center, Department of Neonatology
Jerusalem, 96757
Meir Medical Center, Premature Baby Unit
Kfar Saba, 44410
Kaplan Medical Center Rehovot, Dept. of Neonatology
Rehovot, 76100
Italy5 sites
Ospedale Salesi, SOD Neonatologia
Ancona, 60123
ASO S. Croce e Carie, Terapia Intensiva Neonatale-Neonatologia
Cuneo, 12100
Azienda Ospedaliera di Padova, Dipartimento di Pediatria Salus Pueri
Padova, 35128
Azienda Ospedaliera Universitaria Pisana, U.O. Neonatologia
Pisa, 56100
Ospedale Sant'Anna, Terapia Intensiva Neonatale Clinica -3°piano
Torino, 10126
Belgium4 sites
AZ Sint-Jan Brugge Oostende AV, Department of Neontalogy
Bruges, 8000
CHU St-Pierre, UMC St-Pieter
Brussels, 1000
HUDERF, Department of Neonatology
Brussels, 1020
CHU Tivoli, Department of Neonatology
La Louvière, 7100
France3 sites
CHU de LilleHôpital Jeanne de Flandres, Pôle de Médecine néonataleUnité de Réanimation néonatale
Lille, 59035
Hospital Cochin Saint-Vincent de Paul, Dept. of Neonatology
Paris, 75014
Hôpital Clocheville, Service de RéanimationNéonatale
Tours, 37044
Netherlands1 site
Erasmus MC - Sophia, Department of Neonatology
Rotterdam, 3015
About this study
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%.
Read more
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.
- Conditions
- Bronchopulmonary Dysplasia
- Being tested
- Budesonide
- Keywords
- Preterm Infants, Inhaled Corticosteroids, Bronchopulmonary Dysplasia
- Medical subject headings
- Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BudesonideDrug
Also called Budiair
Inhalation, 200 µg/puff
| Study group | Role | What they receive |
|---|---|---|
| inhaled Budesonide | Experimental | Not described Receives: Drug: Budesonide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival without BPD at 36 weeks GA
Measured: 36 weeks GA
Secondary outcomes (1)
Neurodevelopment at a corrected age of 18 - 22 months.
Measured: 18 - 22 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2009 (estimated)
- Study startApr 2010
- Primary completionOct 2013
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Bronchopulmonary DysplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 863 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Children's Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- European Union
- Responsible party
- Principal investigator, Prof. Dr. med. Dirk Bassler, Msc, University Children's Hospital Tuebingen
- Investigators
- Prof. Dr. med. Dirk Bassler, MSc, Principal investigator, University Children's Hospital Tuebingen / University Hospital Zurich, Department of NeonatologyProf. Dr. med. Christian F Poets, Principal investigator, Children's Hospital, Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01035190
- Sponsor's protocol ID
- GAH-F5_2009-223060
- Acronym
- NEuroSIS
- Status last verified
- Jul 2016
- First submitted
- 17 Dec 2009
- Last updated
- 6 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 19590247Ciora 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.
PubMed 38605404Bassler 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.
PubMed 29320647Bassler 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.
PubMed 26465983
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Inhaled Budesonide in Very Preterm Infants at Risk for Bronchopulmonary Dysplasia
- ClinicalTrials.gov ID
- NCT01035190
- Acronym / sponsor ID
- NEuroSIS / GAH-F5_2009-223060
- Conditions
- Bronchopulmonary Dysplasia
- Keywords
- Preterm Infants, Inhaled Corticosteroids, Bronchopulmonary Dysplasia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 863 participants (actual)
- Lead sponsor
- University Children's Hospital TuebingenUniversity, hospital or other
- Collaborators
- European Union
- Study start
- Apr 2010
- Primary completion
- Oct 2013 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 18 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| inhaled Budesonide | Experimental | Drug: Budesonide |
Who may qualify
- Ages
- Up to 12 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BudesonideAlso: BudiairInhalation, 200 µg/puff | Drug | inhaled Budesonide |
Primary outcome
Survival without BPD at 36 weeks GA
Time frame: 36 weeks GA
1 secondary outcome
Neurodevelopment at a corrected age of 18 - 22 months.
Time frame: 18 - 22 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2016.
- Background: PubMed 19590247Bassler 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.
- Derived from this study: PubMed 38605404Ciora 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.
- Derived from this study: PubMed 29320647Bassler 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.
- Derived from this study: PubMed 26465983Bassler 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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
40 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Budesonide in people with Bronchopulmonary Dysplasia, run by University Children's Hospital Tuebingen at 40 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in Germany, Czechia, Finland, Israel, Italy and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival without BPD at 36 weeks GA (time frame: 36 weeks GA). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01035190, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2016.