Intratracheal Budesonide With Surfactant to Prevent Bronchopulmmonary Dysplasia.

Bronchopulmonary Dysplasia Clinical Trial

— BuS  

Official title:

Efficacy and Safety of the Intratracheal Administration of Budesonide With Porcine Pulmonary Surfactant in Very Preterm Infants to Prevent Bronchopulmonary Dysplasia: Randomized Clinical Trial (BuS Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04862377
• Other study ID #: BuS2020
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: October 1, 2021
• Est. completion date: April 1, 2026

Study information

• Verified date: April 2021
• Source: Hospital Clinic of Barcelona
• Contact: Marta Teresa-Palacio, MD
• Phone: 0034 93 227 56 00
• Email: teresa[@]clinic.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to determine whether intratracheal administration of budesonide combined with surfactant, as compared to surfactant alone, will modify ecographic (lung ultrasound score) and biological markers (IL-6 concentration in respiratory secretions) at 7 days of life in preterm infants ≤32 weeks of gestational age (GA).

Description:

Bronchopulmonary dysplasia (BPD) is one of the main morbidities associated with extreme prematurity and, despite the improvement of respiratory care in the latest years, overall incidence is not decreasing. Etiology of BPD is multifactorial and local inflammation plays an important role in it, therfore, local anti-inflammatory drugs could be effective in preventing BPD.

Recent randomised trials have shown a lower incidence of BPD/death with the use of a combination of budesonide with surfactat compared to surfactant alone, and further clinical trials are currently ongoing.

This is a controlled phase IV, randomised, unicenter clinical trial designed to evaluate the effect of intratracheal administration of budesonide combined with surfactant, as compared to surfactant alone, in BPD in preterm infants ≤32 weeks of GA. Investigators will compare ecographic and biological markers, as well as respiratory outcomes.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: April 1, 2026
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 48 Hours

Eligibility

Inclusion Criteria:

• Infants born equal or earlier than 32 weeks of gestational age admitted in the Neonatal Intensive Care Unit.

• Parental consent signed.

• Less than or equal to 48 hours postnatal age.

Exclusion Criteria:

• Infants with known major congenital anomalies (eg. congenital upper airwayobstruction, congenital lung anomaly, severe pulmonary hypoplasia, hydrops,neuromuscular diseases, chromosomopaties)

• Infants with poor prognosis and risk of imminent death

• Infants who have received the first dose of surfactant before of the enrolment to the study.

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Hyperplasia
• Premature Birth
• Prematurity
• Respiratory Distress Syndrome in Premature Infant
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• Poractant Alfa Intratracheal Suspension [Curosurf]
Poractant alfa (Curosurf®): First dose of treatment: 200mg/Kg. Further doses (up to a total maximum of 3 within first 48 hours of life): 100mg/Kg.
• Budesonide 0.5 MG/ML
Poractant alfa (Curosurf®) + Budesonide nebulizer solution (Budesonida Aldo-Unión 0.5mg/mL suspensión para inhalación por nebulizador®): First dose: 200mg/Kg of surfactant + 0.25mg/Kg of budesonide. Further doses (up to a total maximum of 3 within first 48 hours of life): 100mg/Kg of surfactant + 0.25mg/Kg of budesonide.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona

References & Publications (10)

Aldecoa-Bilbao V, Balcells-Esponera C, Herranz Barbero A, Borràs-Novell C, Izquierdo Renau M, Iriondo Sanz M, Salvia Roigés M. Lung ultrasound for early surfactant treatment: Development and validation of a predictive model. Pediatr Pulmonol. 2021 Feb;56(2):433-441. doi: 10.1002/ppul.25216. Epub 2020 Dec 23. — View Citation

Alonso-Ojembarrena A, Lubián-López SP. Lung ultrasound score as early predictor of bronchopulmonary dysplasia in very low birth weight infants. Pediatr Pulmonol. 2019 Sep;54(9):1404-1409. doi: 10.1002/ppul.24410. Epub 2019 Jun 10. — View Citation

Förster K, Sass S, Ehrhardt H, Mous DS, Rottier RJ, Oak P, Schulze A, Flemmer AW, Gronbach J, Hübener C, Desai T, Eickelberg O, Theis FJ, Hilgendorff A. Early Identification of Bronchopulmonary Dysplasia Using Novel Biomarkers by Proteomic Screening. Am J Respir Crit Care Med. 2018 Apr 15;197(8):1076-1080. doi: 10.1164/rccm.201706-1218LE. — View Citation

Heo M, Jeon GW. Intratracheal administration of budesonide with surfactant in very low birth weight infants to prevent bronchopulmonary dysplasia. Turk J Pediatr. 2020;62(4):551-559. doi: 10.24953/turkjped.2020.04.004. — View Citation

Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. — View Citation

Kuo HT, Lin HC, Tsai CH, Chouc IC, Yeh TF. A follow-up study of preterm infants given budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants. J Pediatr. 2010 Apr;156(4):537-41. doi: 10.1016/j.jpeds.2009.10.049. Epub 2010 Feb 6. — View Citation

Oulego-Erroz I, Alonso-Quintela P, Terroba-Seara S, Jiménez-González A, Rodríguez-Blanco S. Early assessment of lung aeration using an ultrasound score as a biomarker of developing bronchopulmonary dysplasia: a prospective observational study. J Perinatol. 2021 Jan;41(1):62-68. doi: 10.1038/s41372-020-0724-z. Epub 2020 Jul 14. — View Citation

Venkataraman R, Kamaluddeen M, Hasan SU, Robertson HL, Lodha A. Intratracheal Administration of Budesonide-Surfactant in Prevention of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants: A Systematic Review and Meta-Analysis. Pediatr Pulmonol. 2017 Jul;52(7):968-975. doi: 10.1002/ppul.23680. Epub 2017 Feb 6. Review. — View Citation

Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, Tsai CH, Lin HC. Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2016 Jan 1;193(1):86-95. doi: 10.1164/rccm.201505-0861OC. — View Citation

Yeh TF, Lin HC, Chang CH, Wu TS, Su BH, Li TC, Pyati S, Tsai CH. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics. 2008 May;121(5):e1310-8. doi: 10.1542/peds.2007-1973. Epub 2008 Apr 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lung ultrasound score at 7 days of life.	LUS will be performed with the patients in supine position and slightly lying on the side of the taken view. Each lung will be divided in five areas through longitudinal orientation and images will be taken using the linear probe (VF 13-5MHz).	7 days of life
Primary	IL-6 concentration in respiratory secretions at 7 days of life.	Nasopharyngeal aspirate (NPA) will be collected by standard procedure. IL-6 concentration will be determined by Human IL-6 Quantikine ELISA (R&D Systems Inc., Minneapolis, MN, USA).	7 days of life
Secondary	Lung ultrasound score at 28 days of life.	LUS will be performed with the patients in supine position and slightly lying on the side of the taken view. Each lung will be divided in five areas through longitudinal orientation and images will be taken using the linear probe (VF 13-5MHz).	28 days of life
Secondary	IL-6 concentration in respiratory secretions at 28 days of life.	Nasopharyngeal aspirate (NPA) will be collected by standard procedure. IL-6 concentration will be determined by Human IL-6 Quantikine ELISA (R&D Systems Inc., Minneapolis, MN, USA).	28 days of life
Secondary	Number of days of oxygen	Number of days on FiO2 >21% supplied by any respiratory support	7 and 28 days of age, 36 weeks of post-menstrual age.
Secondary	Number of days of respiratory support	Number of days on each level of respiratory support: No respiratory support; Nasal cannula at flow rates = 2L/min; Nasal cannula at flow rates > 2L/min; CPAP/BIPAP; Invasive mechanical ventilation	7 and 28 days of age, 36 weeks of post-menstrual age.
Secondary	Mean airway pressure (MAP)	Maximum MAP mesured in cmH2O at 7 and 28 days of age, 36 weeks of postmenstrual age.	7 and 28 days of age, 36 weeks of post-menstrual age.
Secondary	Incidence of bronchopulmonary dysplasia	BPD will be defined according to the 2001 workshop definition (Jobe AH, Bancalari E. Bronchopulmonary dysplasia. American Journal of Respiratory and Critical Care Medicine. American Lung Association; 2001; pp 1723-9).	36 weeks of post-menstrual age.
Secondary	Respiratory status and neurodevelopment	Neurodevelopment will be assessed using Bayley-III test.	24 months of age.

External Links

•   Risk calculator for surfactant administration