Non Inferiority Trial Investigating Surfactants Administered Via MIST

Study Overview
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Brief Summary
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RESEARCH DESIGN Multicenter, randomized, controlled trial. RECRUITMENT Entry criteria Preterm infants 28-35 6/7 weeks' gestation and less than 48 hours of age who have a clinical diagnosis of respiratory distress syndrome. Infants who on NCPAP and FiO2 ≥0.30 will randomized to curosuf or infasurf via MIST. Exclusion criteria Infants will be excluded if there is a congenital anomaly or an alternative cause for respiratory distress. Babies who require emergent intubation will not be enrolled in the interventions. Parental Consent will be obtained prior to randomization.

Detailed Description
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Entry criteria Preterm infants 28-35 6/7 weeks' gestation and less than 48 hours of age who have a clinical diagnosis of respiratory distress syndrome confirmed by a chest x-ray. Infants who on NCPAP and FiO2 ≥0.30 will randomized to Infasurf of Curosurf via MIST. Exclusion criteria Infants will be excluded if there is a congenital anomaly or an alternative cause for respiratory distress. Babies who require emergent intubation will not be enrolled in the interventions. Parental Consent will be obtained prior to randomization. . INTERVENTION Infants who on CPAP who reach the threshold of 30% oxygen will be randomized to calfactant (Infasurf), 3ml/kg or poractant alfa (Curosurf), 2.5ml/kg, administered under direct laryngoscopy using a surfactant instillation catheter (MIST) 16G Angiocath (Becton Dickinson, Sandy, UT, USA). A second dose of calfactant (Infasurf) 3ml/kg or poractant alfa (Curosurf), 1.25ml/kg, will be administered via MIST their fiO2 reaches the threshold of 30% between 6 and 48 hours after the first dose. No further surfactant should be given in the first 7 days unless the infant reaches the intubation criteria. POST-INTERVENTION MANAGEMENT Other than the requirement to adhere to intubation criteria in the first week, and in some cases perform a room air trial at 36 weeks corrected gestation, management will be at the discretion of the clinical team. Titration of CPAP pressure is encouraged, with a permitted maximum of 8 cm H2O. Use of nasal IPPV is allowable for apnea, but discouraged for RDS and should only be after at least one dose of surfactant has been given. Early caffeine therapy is expected. Criteria for intubation: Enrolled infants on CPAP will be intubated if: FiO2 ≥0.45 for 15 minutes, or if there is unremitting apnea (> 6 episodes/hour requiring intervention or in the opinion of the treating physician) or persistent respiratory acidosis (pH<7.25 and pCO2 >60) on blood gasses at least 30 minutes apart or metabolic acidosis refractory to treatment. Need for an anesthetic or an intervention requiring intubation These criteria apply during the first week of life, and to the first episode of intubation only. If the infant is intubated it is expected that another dose of surfactant will be administered. OUTCOMES Primary outcome: Intubation in the first 7 days of age. Secondary outcomes: Respiratory Number of doses of surfactant, Incidence of composite outcome of death or physiological bronchopulmonary dysplasia (BPD). Durations of mechanical respiratory support, CPAP, high flow nasal cannula, (HFNC), oxygen therapy. Pneumothorax or pulmonary hemorrhage. Non respiratory neonatal morbidities intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotising enterocolitis, and patent ductus arteriosus. Corrected age at discharge, length of hospital stay (a proxy for cost). The above data will be collected until discharge. SAMPLE SIZE With intubation with 7 days as the primary outcome, assuming a baseline of 75% avoiding intubation a total of 262 babies would be needed with an inferiority margin of 15%.

Official Title
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Non Inferiority Trial Investigating Surfactants Administered Via MIST

Conditions
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Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: MIST surfactant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants 28-35 6/7 weeks' gestation and less than 48 hours of age who have a clinical diagnosis of respiratory distress syndrome confirmed by a chest x-ray on nasal continuous positive airway pressure (NCPAP) and FiO2 ≥0.30 Exclusion Criteria: Infants will be excluded if there is a congenital anomaly or an alternative cause for respiratory distress. Infants who require emergent intubation will not be enrolled in the interventions.

Ages Eligible for Study
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Maximum Age: 48 Hours

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: Comparison of the efficacy of calfactant compared to poractant alfa administered with a minimally invasive method for the treatment of respiratory distress syndrome in 28-36 week infants
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calfactant (Infasurf)<br>Neonate, 28-35 weeks gestation, less than 48 hours of age, with respiratory distress syndrome on CPAP > 30% oxygen will be given 3ml/kg of Calfacant | Drug: MIST surfactant<br>* Surfactant will be given via MIST while neonate is on CPAP<br>|
| Experimental: Poractant alfa (Curosurf)<br>Neonate, 28-35 weeks gestation, less than 48 hours of age, with respiratory distress syndrome on CPAP > 30% oxygen will be given 2.5ml/kg of Poractant alfa. | Drug: MIST surfactant<br>* Surfactant will be given via MIST while neonate is on CPAP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endotracheal Intubation | Infants will have an endotracheal placed if their inspired oxygen is >45% for more than 15 minutes | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of positive pressure support | Endotracheal ventilation or Non-invasive Ventilation or CPAP or NC flow>2 L | 36 weeks corrected gestational age | 
| Duration of Supplemental oxygen | Oxygen requirement to keep saturations >95% | 36 weeks corrected gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Surfactant, CPAP, Neonate