InfasurfAero™ Versus Sham Treatment in Preterm Newborns With RDS

Study Overview
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Brief Summary
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The purpose of this clinical study is to determine the effectiveness and safety of Infasurf® administered through the InfasurfAero™, a novel oral airway delivery device specifically designed to give Infasurf in a less complicated way and without the need for a breathing tube or interrupting nasal respiratory support.

Detailed Description
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This single-dose, double-blind, random allocation, sham-control, clinical trial will recruit spontaneously breathing newborns with RDS stable on non-invasive nasal respiratory support. Enrolled clinical study subjects will be randomly allocated to receive respiratory air with Infasurf® (Intervention Arm) or respiratory air alone (Sham Control Arm) through the InfasurfAero™. The objectives of this clinical study are to i) assess the effectiveness of a single dose of Infasurf administered through the InfasurfAero in preventing CPAP failure, and ii) assess the safety of Infasurf administered through the InfasurfAero. Subjects will be enrolled at one of 10+ sites. 7 sites are currently recruited.

Official Title
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InfasurfAero™ Versus Sham Treatment in Preterm Newborns With RDS: A Single-dose, Double-blind, Random Allocation, Sham-control, Clinical Trial

Conditions
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Respiratory Distress Syndrome (Neonatal), Intubation Complication, Death; Neonatal

Intervention / Treatment
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* Combination Product: Infasurf Aero™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria include ALL of the following: Written informed consent obtained by parent or legal representative prior to or after birth Gestational age at birth ≥ 29 0/7 AND ≤ 36 6/7 weeks Birthweight ≥ 1,000 AND ≤ 3,500 grams Age ≥ 1 hour AND ≤ 6 hours Clinical diagnosis of surfactant-deficient RDS, with EITHER i. a Silverman-Anderson Retraction Score ≥ 5 (in Room Air), OR ii. signs of respiratory distress (tachypnea, retractions, grunting) AND radiographic confirmation Require non-invasive respiratory support (i.e., continuous positive airway pressure or non-invasive ventilation) Respiratory Severity Score (RSS) ≥ 1.25 AND ≤ 2.4 Exclusion Criteria: Exclusion criteria are ANY of the following: Surfactant administration prior to randomization Mechanical ventilation prior to randomization Major congenital anomaly (suspected or confirmed) Abnormality of the airway (suspected or confirmed) Respiratory distress presumed secondary to an etiology other than RDS (e.g., suspected pulmonary hypoplasia, pneumothorax, meconium aspiration syndrome, pneumonia, septic or hypovolemia shock, hypoxic ischemic encephalopathy) Culture-positive bacterial sepsis requiring at least 5 days of antibiotic therapy Apgar score < 3 at 5 minutes of age Umbilical cord gas pH <7.0 or BD > 10 Any condition that, in the opinion of the Investigator, would place the neonate at undue risk

Ages Eligible for Study
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Minimum Age: 29 Weeks
Maximum Age: 36 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
Interventional Model Description: This single-dose, double-blind, random allocation, sham-control, clinical trial will recruit spontaneously breathing newborns with RDS stable on non-invasive nasal respiratory support. Enrolled clinical study subjects will be randomly allocated to receive respiratory air with Infasurf® (Intervention Arm) or respiratory air alone (Sham Control Arm) through the InfasurfAero™.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>A single dose of Calfactant at 6ml/kg administered via the Infasurf Aero™ Nebulizer until completion. | Combination Product: Infasurf Aero™<br>* A single dose of Calfactant administered by pacifier interface by inhalation via the Infasurf Aero nebulizer at 6ml/kg.<br>|
| Sham Comparator: Control Arm<br>Low flow respiratory air alone through the InfasurfAero™ Nebulizer until completion. | Combination Product: Infasurf Aero™<br>* A single dose of Calfactant administered by pacifier interface by inhalation via the Infasurf Aero nebulizer at 6ml/kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CPAP failure and or death | CPAP failure is defined as a respiratory severity score (RSS) (MAP x FiO2) >2.5 on two consecutive assessments at least 30 minutes apart, or an RSS > 2.4 and one or more of the following: (i) Silverman-Andersen respiratory severity score (https://www.thecalculator.co/health/Silverman-Score-Calculator-1125.html) of ≥ 5 despite respiratory support. (ii) Severe apnea (2 or more episodes per hour, or 1 or more episodes requiring manual positive pressure ventilation). (iii) Respiratory acidosis (pCO2 > 65 with a pH < 7.2 on blood gas). RSS will be the primary indicator of CPAP failure. However with the addition of the Silverman-Anderson scores, severe apnea and respiratory acidosis, CPAP failure may occur earlier than solely defined by RSS score. | Within 1st week of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic lung disease and or death | Chronic lung disease is defined as altitude adjusted oxygen requirement at 36 weeks post menstrual age. | 36 weeks post menstrual age (PMA). | 
| Incidence of MV | Incidence of Mechanical Ventilation | 36 weeks PMA | 
| Duration of MV | length of time of Mechanical Ventilation | 36 weeks PMA | 
| Incidence of intubation | Any occurrence of tracheal intubation | 36 weeks PMA | 
| Incidence of invasive surfactant replacement therapy | any occurrence of liquid surfactant administration via and endotracheal tube | 72 hours post birth | 
| Duration of non-invasive support | Length of time of respiratory support other than Intubation | 36 weeks PMA | 
| Duration of supplemental oxygen | Length of time any oxygen is administered. | 36 weeks PMA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neonatal, Infasurf, Calfactant, Inhalation, Nebulization, Preterm, InfasurfAero, Respiratory Distress Syndrome, NICU, CPAP, Intubation, Aerosol, CPAP Failure