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

NCT01035190 | Completed Phase 3 DMC

• 1 other identifier: GAH-F5_2009-223060
• Study Type: interventional
• Target: 863
• Locations: 8 countries
• Sites: 40

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.

Conditions

Bronchopulmonary Dysplasia

Keywords

Preterm Infants; Inhaled Corticosteroids; Bronchopulmonary Dysplasia

Outcome Measures

Primary Outcomes (1)

• Survival without BPD at 36 weeks GA

  36 weeks GA

Secondary Outcomes (1)

• Neurodevelopment at a corrected age of 18 - 22 months.

  18 - 22 months

Study Arms (1)

inhaled Budesonide

EXPERIMENTAL

Drug: Budesonide

Interventions

Budesonide DRUG

Inhalation, 200 µg/puff

Also known as: Budiair

inhaled Budesonide

Eligibility Criteria

• Age: Up to 12 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Children's Hospital Tuebingen: lead
• European Union: collaborator

Study Sites (40)

AZ Sint-Jan Brugge Oostende AV, Department of Neontalogy

Bruges, 8000, Belgium

Location

CHU St-Pierre, UMC St-Pieter

Brussels, 1000, Belgium

Location

HUDERF, Department of Neonatology

Brussels, 1020, Belgium

Location

CHU Tivoli, Department of Neonatology

La Louvière, 7100, Belgium

Location

University Hospital Brno, Department of Neonatology

Brno, 62500, Czechia

Location

University Hospital Ostrava, Department of Neonatology

Ostrava, 70852, Czechia

Location

University Hospital Plzen, Department of Neonatology

Pilsen, 30599, Czechia

Location

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

Prague, 12800, Czechia

Location

University Hospital Motol Prague 5, Department of Neonatology

Prague, 15006, Czechia

Location

University Hospital of Tomas Bati, Department of Neonatology

Zlín, 76201, Czechia

Location

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

Helsinki, 00029, Finland

Location

University Hospital Kuopio, NICU

Kuopio, 70211, Finland

Location

Oulu University Hospital

Oulu, 90220, Finland

Location

Tampere University Hospita, NICU

Tampere, 33521, Finland

Location

Tartu University Children's Clinic, Paediatric Intensive Care Unit

Tartu, 50406, Finland

Location

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

Lille, 59035, France

Location

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

Paris, 75014, France

Location

Hôpital Clocheville, Service de RéanimationNéonatale

Tours, 37044, France

Location

University Children's Hospital Aachen, Dept. of Neonatology

Aachen, 52074, Germany

Location

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

Dresden, 01307, Germany

Location

University Children's Hospital Erlangen, Dept. of Neonatology

Erlangen, 91054, Germany

Location

University Children's Hospital Essen, Dept. of Pediatrics

Essen, 45147, Germany

Location

Georg-August University Hospital Goettingen, Dept. of Pediatrics

Göttingen, 37075, Germany

Location

University Hospital Hamburg-Eppendorf, Dept. of Neonatology

Hamburg, 20246, Germany

Location

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

Hanover, 30173, Germany

Location

University Hospital Hannover, Dept. of Neonatology

Hanover, 30625, Germany

Location

University Children's Hospital Heidelberg, Dept. of Neonatology

Heidelberg, 69120, Germany

Location

Hospital Nuernberg Sued, Dept. of Neonatology

Nuremberg, 90471, Germany

Location

University Children´s Hospital Tuebingen, Dept. of Neonatology

Tübingen, 72076, Germany

Location

Ben-Gurion University of NegevSoroka Medical Center, Neonatal Department

Beersheba, 84101, Israel

Location

Bnai Zion Medical Center Haifa, Department of Neonatology

Haifa, 31048, Israel

Location

Hadassah Medical Center, Department of Neonatology

Jerusalem, 96757, Israel

Location

Meir Medical Center, Premature Baby Unit

Kfar Saba, 44410, Israel

Location

Kaplan Medical Center Rehovot, Dept. of Neonatology

Rehovot, 76100, Israel

Location

Ospedale Salesi, SOD Neonatologia

Ancona, 60123, Italy

Location

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

Cuneo, 12100, Italy

Location

Azienda Ospedaliera di Padova, Dipartimento di Pediatria Salus Pueri

Padua, 35128, Italy

Location

Azienda Ospedaliera Universitaria Pisana, U.O. Neonatologia

Pisa, 56100, Italy

Location

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

Torino, 10126, Italy

Location

Erasmus MC - Sophia, Department of Neonatology

Rotterdam, 3015, Netherlands

Location

Related Publications (4)

• 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.

  PMID: 19590247 BACKGROUND

• 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.

  PMID: 38605404 DERIVED

• 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.

  PMID: 29320647 DERIVED

• 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.

  PMID: 26465983 DERIVED

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Prof. Dr. med. Dirk Bassler, MSc

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

  PRINCIPAL INVESTIGATOR

• Prof. Dr. med. Christian F Poets

  Children's Hospital, Tuebingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.Dr. med.

Study Record Dates

• First Submitted: December 17, 2009
• First Posted: December 18, 2009
• Study Start: April 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: July 1, 2016
• Last Updated: July 6, 2016

Record last verified: 2016-07

Locations

BE (4); CZ (6); FI (5); IL (5); FR (3); NL (1); IT (5); DE (11)