Medium vs Low Oxygen Threshold for the Surfactant Administration

Study Overview
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Brief Summary
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The aim of this study will be to assess the better fraction inspired oxygen (FiO2) threshold for the surfactant treatment in preterm infants with respiratory distress syndrome (RDS) randomized to receive exogenous surfactant at 25% or 35% of FiO2 threshold. The pulmonary gas-exchanges will be evaluated by oxygen saturation (SpO2) to FiO2 ratio (SFR) and will be used to define the better FiO2 threshold for the surfactant treatment.

Detailed Description
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Exogenous surfactant therapy is an effective treatment of neonatal respiratory distress syndrome (RDS) and has been associated with reduced severity of respiratory distress and mortality. The 2019 European guidelines for neonatal RDS treatment suggest as the threshold of inspired oxygen (FiO2) for the surfactant treatment at 30% for all gestational age, but there are no randomized studies that confirm this indication. Some observational studies reported that a relevant number of patients who are not routinely treated with surfactant had respiratory complications, thus they received exogenous surfactant. To date, the optimal FiO2 threshold for surfactant administration remains unclear. In this single-center, randomized, phase 4 trial, preterm infants (gestational age<32 weeks) with RDS will be randomized to receive exogenous surfactant at 25% or 35% of FiO2 threshold. According to the unit policy, the exogenous surfactant will be administered by an endotracheal tube in intubated infants, or by Intubation-Surfactant-Extubation (InSurE) / Less Invasive Surfactant Administration (LISA) methods in infants who will not remain intubated. The method used for the surfactant administration will be at the discretion of the caring physician.

Official Title
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Comparison of Two Fraction Oxygen Inspired (FiO2) Thresholds for the Surfactant Administration in Preterm Infants With Respiratory Disease Syndrome: a Single-center Randomized Phase IV Clinical Trial

Conditions
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Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Poractant Alfa 80 mg/mL Intratracheal Suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: gestational age less than 32 weeks; diagnosis of respiratory distress (RDS); need for ventilatory support; written informed consent. Exclusion Criteria: congenital malformations; genetic disorders; perinatal asphyxia. neonatal pneumonia or wet lung or meconium aspiration syndrome at birth.

Ages Eligible for Study
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Minimum Age: 24 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low FiO2 threshold<br>A fraction of inspired oxygen (FiO2) of 25% to have an oxygen saturation (SpO2) of 90-92%. | Drug: Poractant Alfa 80 mg/mL Intratracheal Suspension<br>* Exogenous surfactant (Poractant Alfa) administration at a dose of 200 mg/kg.<br>|
| Experimental: Medium FiO2 threshold<br>A fraction of inspired oxygen (FiO2) of 35% to have an oxygen saturation (SpO2) of 90-92%. | Drug: Poractant Alfa 80 mg/mL Intratracheal Suspension<br>* Exogenous surfactant (Poractant Alfa) administration at a dose of 200 mg/kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory pulmonary function | The oxygen saturation (SpO2) to fraction of inspired oxygen (FiO2) ratio (SFR) | At day 3 of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endotracheal intubation | The need of endotracheal intubation after surfactant administration | At day 3, 7 and 28 of life, and at 36 weeks of postmenstrual age or at the discharge if it occurs first | 
| Oxygen therapy | The need of oxygen therapy | At day 3, 7 and 28 of life, and at 36 weeks of postmenstrual age or at the discharge if it occurs first | 
| Respiratory Support-1 | The need of respiratory support | At day 3, 7 and 28 of life, and at 36 weeks of postmenstrual age or at the discharge if it occurs first | 
| Respiratory Support-1 | Oxygenation index as indicator of the intensity of ventilatory | At day 3, 7 and 28 of life, and at 36 weeks of postmenstrual age or at the discharge if it occurs first | 
| Respiratory severity-1 | Silvermann score as secondary respiratory severity index | At day 3, 7 and 28 of life, and at 36 weeks of postmenstrual age or at the discharge if it occurs first | 
| Respiratory severity-2 | Lung ultrasound score (LUS) score as secondary respiratory severity index | At day 3, 7 and 28 of life, and at 36 weeks of postmenstrual age or at the discharge if it occurs first | 
| Long-term respiratory pulmonary function | The oxygen saturation (SpO2) to fraction of inspired oxygen (FiO2) ratio (SFR) | At day 7 and 28 of life, and at 36 weeks of postmenstrual age or at the discharge if it occurs first, and 1 year of corrected age | 
| Complications of prematurity | The incidence of intraventricular hemorrhage of grade 3-4, periventricular leukomalacia, bronchopulmonary dysplasia, sepsis and retinopathy of prematurity | From birth to 36 weeks of postmenstrual age or discharge if it occurred first | 
| In-hospital death | death before 36 weeks of gestation | From birth to 36 week of gestation or discharge if it occurred first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RDS, Surfactant, Threshold, Oxygen, Preterm, Infant