Clinical trial NCT04862377: Intratracheal Budesonide With Surfactant to Prevent Bronchopulmmonary Dysplasia.
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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Bronchopulmonary Dysplasia
Respiratory Distress Syndrome in Premature Infant
Prematurity
Keywords: Bronchopulmonary dysplasia
Respiratory Distress Syndrome in premature infant
Prematurity
Lung injury
Poractant alfa
Pulmonary surfactant
Budesonide
Anti-inflammatory agents
Glucocorticoids
Lung ultrasound
IL-6
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
First posted: 2021-04-28
Enrollment: 50
Sex: ALL
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomised trial. Infants who fit criteria for surfactante administration will be randomly assigned into 2 groups: "Standard treatment group" receiving only intratracheal surfactant, and "Interventional treatment group" receiving intratracheal surfactant combined with budesoinde.

It will be a third group of patients ≤32 weeks ("Control group") who won´t fit criteria for surfactant administration.
Primary purpose: PREVENTION

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Lung ultrasound score at 7 days of life.
timeFrame: 7 days of life
measure: IL-6 concentration in respiratory secretions at 7 days of life.
timeFrame: 7 days of life
Secondary outcomes:
measure: Lung ultrasound score at 28 days of life.
timeFrame: 28 days of life
measure: IL-6 concentration in respiratory secretions at 28 days of life.
timeFrame: 28 days of life
measure: Number of days of oxygen
timeFrame: 7 and 28 days of age, 36 weeks of post-menstrual age.
measure: Number of days of respiratory support
timeFrame: 7 and 28 days of age, 36 weeks of post-menstrual age.
measure: Mean airway pressure (MAP)
timeFrame: 7 and 28 days of age, 36 weeks of post-menstrual age.
measure: Incidence of bronchopulmonary dysplasia
timeFrame: 36 weeks of post-menstrual age.
measure: Respiratory status and neurodevelopment
timeFrame: 24 months of age.
Other outcomes:
Locations:
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Marta Teresa-Palacio, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Oulego-Erroz I, Alonso-Quintela P, Terroba-Seara S, Jimenez-Gonzalez A, Rodriguez-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.
citation: Alonso-Ojembarrena A, Lubian-Lopez 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.
citation: Forster K, Sass S, Ehrhardt H, Mous DS, Rottier RJ, Oak P, Schulze A, Flemmer AW, Gronbach J, Hubener 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. No abstract available.
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.
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.
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.
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.
citation: Aldecoa-Bilbao V, Balcells-Esponera C, Herranz Barbero A, Borras-Novell C, Izquierdo Renau M, Iriondo Sanz M, Salvia Roiges 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.
citation: Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. doi: 10.1164/ajrccm.163.7.2011060. No abstract available.