Intratracheal Budesonide With Surfactant to Prevent Bronchopulmmonary Dysplasia.

NCT04862377 | Not Yet Recruiting Phase 3

• 1 other identifier: BuS2020
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

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).

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (7)

• Lung ultrasound score at 28 days of life.

  28 days of life

• IL-6 concentration in respiratory secretions at 28 days of life.

  28 days of life

• Number of days of oxygen

  7 and 28 days of age, 36 weeks of post-menstrual age.

• Number of days of respiratory support

  7 and 28 days of age, 36 weeks of post-menstrual age.

• Mean airway pressure (MAP)

  7 and 28 days of age, 36 weeks of post-menstrual age.

Study Arms (3)

Standard treatment group

ACTIVE COMPARATOR

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).

Drug: Poractant Alfa Intratracheal Suspension [Curosurf]

Interventional treatment group

EXPERIMENTAL

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.

Drug: Poractant Alfa Intratracheal Suspension [Curosurf]; Drug: Budesonide 0.5 MG/ML

Control group

NO INTERVENTION

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

Interventions

Poractant Alfa Intratracheal Suspension [Curosurf] DRUG

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.

Also known as: Curosurf®

Interventional treatment group; Standard treatment group

Budesonide 0.5 MG/ML DRUG

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.

Also known as: Budesonida Aldo-Unión 0.5mg/mL suspensión para inhalación por nebulizador®

Interventional treatment group

Eligibility Criteria

• Age: Up to 48 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead

Related Publications (10)

• 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.

  PMID: 32779407 BACKGROUND

• 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.

  PMID: 32665687 BACKGROUND

• 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.

  PMID: 31216121 BACKGROUND

• 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.

  PMID: 29053024 BACKGROUND

• 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.

  PMID: 28165675 BACKGROUND

• 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.

  PMID: 26351971 BACKGROUND

• 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.

  PMID: 20138301 BACKGROUND

• 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.

  PMID: 18426851 BACKGROUND

• 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.

  PMID: 33369257 BACKGROUND

• 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.

  PMID: 11401896 BACKGROUND

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth; Lung Injury

Interventions

poractant alfa; Budesonide

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Thoracic Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

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

Study Officials

• Marta Teresa-Palacio, MD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marta Teresa-Palacio, MD

CONTACT

0034 93 227 56 00; teresa@clinic.cat

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 5, 2021
• First Posted: April 28, 2021
• Study Start: October 1, 2021
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2026
• Last Updated: September 13, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share