Intratracheal Budesonide With Surfactant to Prevent Bronchopulmmonary Dysplasia.

NCT ID: NCT04862377

Last Updated: 2021-09-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-01

Study Completion Date

2026-04-01

Brief Summary

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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

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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.

Conditions

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Bronchopulmonary Dysplasia Respiratory Distress Syndrome in Premature Infant Prematurity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants
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.

Study Groups

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Standard treatment group

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).

Group Type ACTIVE_COMPARATOR

Poractant Alfa Intratracheal Suspension [Curosurf]

Intervention Type 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.

Interventional treatment group

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.

Group Type EXPERIMENTAL

Poractant Alfa Intratracheal Suspension [Curosurf]

Intervention Type 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.

Budesonide 0.5 MG/ML

Intervention Type 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.

Control group

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Curosurf® Budesonida Aldo-Unión 0.5mg/mL suspensión para inhalación por nebulizador®

Eligibility Criteria

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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.
Maximum Eligible Age

48 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Clinic of Barcelona

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marta Teresa-Palacio, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic of Barcelona

Central Contacts

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Marta Teresa-Palacio, MD

Role: CONTACT

0034 93 227 56 00 ext. 7503

References

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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.

Reference Type BACKGROUND
PMID: 32779407 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32665687 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31216121 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29053024 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28165675 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26351971 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20138301 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18426851 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33369257 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11401896 (View on PubMed)

Other Identifiers

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BuS2020

Identifier Type: -

Identifier Source: org_study_id

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