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

Phase 3

Completed

• Conditions: Bronchopulmonary Dysplasia
• Interventions: Drug: Budesonide

• Registration Number: NCT01035190
• Lead Sponsor: University Children's Hospital Tuebingen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-12-17
• Study First Submitted QC: 2009-12-17
• Study First Posted: 2009-12-18
• Study Start: 2010-04
• Primary Completion: 2013-10
• Status Verified: 2016-07
• Study Completion: 2016-07
• Last Update Submitted: 2016-07-04
• Last Update Posted: 2016-07-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 863

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
inhaled Budesonide	Budesonide	-

Primary Outcome Measures

Name	Time	Method
Survival without BPD at 36 weeks GA	36 weeks GA

Secondary Outcome Measures

Name	Time	Method
Neurodevelopment at a corrected age of 18 - 22 months.	18 - 22 months

Trial Locations

Locations (40)

University Hospital of Tomas Bati, Department of Neonatology; 🇨🇿 Zlin, Czech Republic

Tampere University Hospita, NICU; 🇫🇮 Tampere, Finland

Erasmus MC - Sophia, Department of Neonatology; 🇳🇱 Rotterdam, Netherlands

University Hospital Brno, Department of Neonatology; 🇨🇿 Brno, Czech Republic

CHU St-Pierre, UMC St-Pieter; 🇧🇪 Brussels, Belgium

CHU Tivoli, Department of Neonatology; 🇧🇪 La Louvière, Belgium

Oulu University Hospital; 🇫🇮 Oulu, Finland

Children's Hospital Hannover auf der Bult, Dept. of Neonatology; 🇩🇪 Hannover, Germany

HUDERF, Department of Neonatology; 🇧🇪 Bruxelles, Belgium

University Hospital Plzen, Department of Neonatology; 🇨🇿 Plzen, Czech Republic

University Hospital Kuopio, NICU; 🇫🇮 Kuopio, Finland

CHU de LilleHôpital Jeanne de Flandres, Pôle de Médecine néonataleUnité de Réanimation néonatale; 🇫🇷 Lille, France

Tartu University Children's Clinic, Paediatric Intensive Care Unit; 🇫🇮 Tartu, Finland

University Hospital Hamburg-Eppendorf, Dept. of Neonatology; 🇩🇪 Hamburg, Germany

University Children's Hospital Essen, Dept. of Pediatrics; 🇩🇪 Essen, Germany

Azienda Ospedaliera Universitaria Pisana, U.O. Neonatologia; 🇮🇹 Pisa, Italy

Ospedale Sant'Anna, Terapia Intensiva Neonatale Clinica -3°piano; 🇮🇹 Torino, Italy

University Children´s Hospital Tuebingen, Dept. of Neonatology; 🇩🇪 Tuebingen, Germany

Ospedale Salesi, SOD Neonatologia; 🇮🇹 Ancona, Italy

AZ Sint-Jan Brugge Oostende AV, Department of Neontalogy; 🇧🇪 Brugge, Belgium

Charles University, General Faculty Hospital and 1st Faculty of Medicine, Department of Obstetrics and Gynecology; 🇨🇿 Prague 2, Czech Republic

University Hospital Ostrava, Department of Neonatology; 🇨🇿 Ostrava, Czech Republic

Hospital Cochin Saint-Vincent de Paul, Dept. of Neonatology; 🇫🇷 Paris, France

Hôpital Clocheville, Service de RéanimationNéonatale; 🇫🇷 Tours, France

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

Georg-August University Hospital Goettingen, Dept. of Pediatrics; 🇩🇪 Goettingen, Germany

University Hospital Hannover, Dept. of Neonatology; 🇩🇪 Hannover, Germany

Hospital Nuernberg Sued, Dept. of Neonatology; 🇩🇪 Nuernberg, Germany

Bnai Zion Medical Center Haifa, Department of Neonatology; 🇮🇱 Haifa, Israel

Ben-Gurion University of NegevSoroka Medical Center, Neonatal Department; 🇮🇱 Beer Sheva, 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, Israel

ASO S. Croce e Carie, Terapia Intensiva Neonatale-Neonatologia; 🇮🇹 Cuneo, Italy

Azienda Ospedaliera di Padova, Dipartimento di Pediatria Salus Pueri; 🇮🇹 Padova, Italy

University Children's Hospital Heidelberg, Dept. of Neonatology; 🇩🇪 Heidelberg, Germany

Helsinki University Central Hospital,Hospital for Children and Adolescents, NICU; 🇫🇮 Helsinki, Finland

University Hospital Motol Prague 5, Department of Neonatology; 🇨🇿 Prague 5, Czech Republic