Phase 1/2 Study of Aerosolized Survanta for the Treatment of Neonatal Respiratory Distress Syndrome

Wayne State University, Detroit MI

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Respiratory distress syndrome (RDS), caused by surfactant deficiency, is the leading cause of mortality and morbidity in preterm infants. Intratracheal instillation, the only approved means of surfactant delivery, requires endotracheal intubation and mechanical ventilation with their attendant risks. Interventions that decrease need for intubation and mechanical ventilation (MV) like noninvasive ventilation (NIV) including nasal continuous positive airway pressure, high flow nasal cannula or nasal intermittent mandatory ventilation are increasingly being used for initial respiratory support in preterm neonates with RDS to improve outcomes. However, the use of NIV not only averts the need for intubation and mechanical ventilation, but also delays surfactant administration. Therefore, aerosolized surfactant delivered during NIV is expected to be an innovative and promising concept for the treatment of RDS by retaining the advantages of early surfactant with alveolar recruitment while obviating the risks of intubation and mechanical ventilation. The investigators' overall hypothesis is that treatment of RDS with aerosolized surfactant in preterm infants undergoing NIV is safe and feasible and will result in short-term improvement in oxygenation and ventilation thus leading to a decrease in need for intensive care support, complications of prematurity, duration of hospitalization and health care costs. The objective of this proposal is to perform a single-center, unblinded, Phase 1/2, randomized clinical trial of aerosolized surfactant for the treatment of RDS in preterm neonates undergoing NIV. The investigators will achieve this objective by addressing the following Specific Aims: Specific Aim 1: Evaluate safety and feasibility of aerosolized surfactant generated with two nebulizers approved for use in neonates - the MiniHeart Lo-Flo jet & the AeroNeb Solo vibrating mesh nebulizer. Safety will be evaluated by monitoring cardiorespiratory parameters, blockage of NIV circuit, nasal trauma scores & cerebral oxygenation. Feasibility will be assessed in terms of tolerance by both the infant & clinical caregivers. Specific Aim 2: Determine the optimal dilution and dose of aerosolized surfactant for treatment of RDS in preterm neonates undergoing NIV. Infants will be randomized to 2 doses and 2 dilutions of aerosolized surfactant resulting in 4 dosing schedules. Specific Aim 3: Evaluate short term efficacy of aerosolized surfactant as assessed by need for intubation and MV in the first 72 hours of life. Efficacy of aerosol delivery will also be assessed by change in surfactant activity in gastric aspirates after aerosolized surfactant. Additional secondary efficacy measures include respiratory severity score, diagnosis of patent ductus arteriosus, need for blood transfusions, postnatal growth, duration of respiratory support, length of hospital stay, incidence of complications of prematurity and death.