search
Back to results

Intratracheal Budesonide With Surfactant to Prevent Bronchopulmmonary Dysplasia. (BuS)

Primary Purpose

Bronchopulmonary Dysplasia, Respiratory Distress Syndrome in Premature Infant, Prematurity

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Poractant Alfa Intratracheal Suspension [Curosurf]
Budesonide 0.5 MG/ML
Sponsored by
Hospital Clinic of Barcelona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Bronchopulmonary Dysplasia focused on measuring Bronchopulmonary dysplasia, Respiratory Distress Syndrome in premature infant, Prematurity, Lung injury, Poractant alfa, Pulmonary surfactant, Budesonide, Anti-inflammatory agents, Glucocorticoids, Lung ultrasound, IL-6

Eligibility Criteria

undefined - 48 Hours (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Active Comparator

    Experimental

    No Intervention

    Arm Label

    Standard treatment group

    Interventional treatment group

    Control group

    Arm Description

    Infants randomised to the "standard treatment" arm will receive intratracheal surfactant as per usual clinical indications of respiratory distress syndrome in these preterm infants. In that sense, and based in those clinical indications, we have developed a risk calculator for surfactant administration in preterm infants ≤32 weeks GA. We will use it to decide what patients will receive surfactant (calculator available on: https://1drv.ms/x/s!Arjkl83HIXSngP8TWh8O6oi6Ztdw3w?e=gNCMxP).

    Infants randomised to the "interventional treatment" arm will receive intratracheal surfactant mixed with budesonide. Indication of surfactant, as equal as for the "standard treatment" arm, will be decided using the calculator.

    Infants ≤32 weeks with no indications for surfactant administration. Their clinical management will be the usual in our neonatal unit.

    Outcomes

    Primary Outcome Measures

    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).
    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).

    Secondary Outcome Measures

    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).
    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).
    Number of days of oxygen
    Number of days on FiO2 >21% supplied by any respiratory support
    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
    Mean airway pressure (MAP)
    Maximum MAP mesured in cmH2O at 7 and 28 days of age, 36 weeks of postmenstrual age.
    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).
    Respiratory status and neurodevelopment
    Neurodevelopment will be assessed using Bayley-III test.

    Full Information

    First Posted
    March 5, 2021
    Last Updated
    September 6, 2021
    Sponsor
    Hospital Clinic of Barcelona
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT04862377
    Brief Title
    Intratracheal Budesonide With Surfactant to Prevent Bronchopulmmonary Dysplasia.
    Acronym
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2021 (Anticipated)
    Primary Completion Date
    April 1, 2024 (Anticipated)
    Study Completion Date
    April 1, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Hospital Clinic of Barcelona

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    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

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    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.
    Masking
    Participant
    Masking Description
    When eligibility of an infant is confirmed, consent will be obtained. Infants candidates to surfactant administration will be randomly assigned to either receive surfactant with budesonide, or surfactant alone, using a web-based randomisation system with an allocation ratio of 1:1. Primary care provider in charge of the patient at the time of the enrolment will be responsible for the randomization, and for the preparation of the drug (surfactant alone, or surfactant with budesonide). Participants will be masked.
    Allocation
    Randomized
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Standard treatment group
    Arm Type
    Active Comparator
    Arm Description
    Infants randomised to the "standard treatment" arm will receive intratracheal surfactant as per usual clinical indications of respiratory distress syndrome in these preterm infants. In that sense, and based in those clinical indications, we have developed a risk calculator for surfactant administration in preterm infants ≤32 weeks GA. We will use it to decide what patients will receive surfactant (calculator available on: https://1drv.ms/x/s!Arjkl83HIXSngP8TWh8O6oi6Ztdw3w?e=gNCMxP).
    Arm Title
    Interventional treatment group
    Arm Type
    Experimental
    Arm Description
    Infants randomised to the "interventional treatment" arm will receive intratracheal surfactant mixed with budesonide. Indication of surfactant, as equal as for the "standard treatment" arm, will be decided using the calculator.
    Arm Title
    Control group
    Arm Type
    No Intervention
    Arm Description
    Infants ≤32 weeks with no indications for surfactant administration. Their clinical management will be the usual in our neonatal unit.
    Intervention Type
    Drug
    Intervention Name(s)
    Poractant Alfa Intratracheal Suspension [Curosurf]
    Other Intervention Name(s)
    Curosurf®
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Budesonide 0.5 MG/ML
    Other Intervention Name(s)
    Budesonida Aldo-Unión 0.5mg/mL suspensión para inhalación por nebulizador®
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Lung ultrasound score at 7 days of life.
    Description
    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).
    Time Frame
    7 days of life
    Title
    IL-6 concentration in respiratory secretions at 7 days of life.
    Description
    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).
    Time Frame
    7 days of life
    Secondary Outcome Measure Information:
    Title
    Lung ultrasound score at 28 days of life.
    Description
    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).
    Time Frame
    28 days of life
    Title
    IL-6 concentration in respiratory secretions at 28 days of life.
    Description
    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).
    Time Frame
    28 days of life
    Title
    Number of days of oxygen
    Description
    Number of days on FiO2 >21% supplied by any respiratory support
    Time Frame
    7 and 28 days of age, 36 weeks of post-menstrual age.
    Title
    Number of days of respiratory support
    Description
    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
    Time Frame
    7 and 28 days of age, 36 weeks of post-menstrual age.
    Title
    Mean airway pressure (MAP)
    Description
    Maximum MAP mesured in cmH2O at 7 and 28 days of age, 36 weeks of postmenstrual age.
    Time Frame
    7 and 28 days of age, 36 weeks of post-menstrual age.
    Title
    Incidence of bronchopulmonary dysplasia
    Description
    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).
    Time Frame
    36 weeks of post-menstrual age.
    Title
    Respiratory status and neurodevelopment
    Description
    Neurodevelopment will be assessed using Bayley-III test.
    Time Frame
    24 months of age.

    10. Eligibility

    Sex
    All
    Maximum Age & Unit of Time
    48 Hours
    Accepts Healthy Volunteers
    No
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Marta Teresa-Palacio, MD
    Phone
    0034 93 227 56 00
    Ext
    7503
    Email
    teresa@clinic.cat
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Marta Teresa-Palacio, MD
    Organizational Affiliation
    Hospital Clinic of Barcelona
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    32779407
    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.
    Results Reference
    background
    PubMed Identifier
    32665687
    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.
    Results Reference
    background
    PubMed Identifier
    31216121
    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.
    Results Reference
    background
    PubMed Identifier
    29053024
    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.
    Results Reference
    background
    PubMed Identifier
    28165675
    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.
    Results Reference
    background
    PubMed Identifier
    26351971
    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.
    Results Reference
    background
    PubMed Identifier
    20138301
    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.
    Results Reference
    background
    PubMed Identifier
    18426851
    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.
    Results Reference
    background
    PubMed Identifier
    33369257
    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.
    Results Reference
    background
    PubMed Identifier
    11401896
    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.
    Results Reference
    background

    Learn more about this trial

    Intratracheal Budesonide With Surfactant to Prevent Bronchopulmmonary Dysplasia.

    We'll reach out to this number within 24 hrs