BuS: Intratracheal Budesonide With Surfactant to Prevent Bronchopulmmonary Dysplasia.

Sponsor

Hospital Clinic of Barcelona (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04862377

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Bronchopulmonary Dysplasia Respiratory Distress Syndrome in Premature Infant Prematurity	Drug: Poractant Alfa Intratracheal Suspension [Curosurf] Drug: Budesonide 0.5 MG/ML	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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:

Single (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.

Primary Purpose:

Prevention

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)

Anticipated Study Start Date :

Oct 1, 2021

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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).	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. Other Names: Curosurf®
Experimental: 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.	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. Other Names: Curosurf® 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. Other Names: Budesonida Aldo-Unión 0.5mg/mL suspensión para inhalación por nebulizador®
No Intervention: Control group Infants ≤32 weeks with no indications for surfactant administration. Their clinical management will be the usual in our neonatal unit.

Arm

Intervention/Treatment

Active Comparator: 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).

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.

Other Names:

Curosurf®

Experimental: 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.

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.

Other Names:

Curosurf®

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.

Other Names:

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

No Intervention: Control group

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

Outcome Measures

Primary Outcome Measures

Lung ultrasound score at 7 days of life. [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. [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. [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. [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 [7 and 28 days of age, 36 weeks of post-menstrual age.]
Number of days on FiO2 >21% supplied by any respiratory support
Number of days of respiratory support [7 and 28 days of age, 36 weeks of post-menstrual age.]
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) [7 and 28 days of age, 36 weeks of post-menstrual age.]
Maximum MAP mesured in cmH2O at 7 and 28 days of age, 36 weeks of postmenstrual age.
Incidence of bronchopulmonary dysplasia [36 weeks of post-menstrual age.]
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 [24 months of age.]
Neurodevelopment will be assessed using Bayley-III test.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 48 Hours

Sexes Eligible for Study:

All

Accepts 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.