Aerosolized Surfactant in Neonatal RDS (AS-02)

Sood, Beena G., MD, MS

Status and phase: Completed; Phase 2; Phase 1

Conditions: Respiratory Distress Syndrome, Newborn

Treatments: Drug: Surfactant

Study type: Interventional

Identifiers

NCT02294630

FD004793 (Other Identifier)

1R01FD004793-01A1

1206011023

Details and patient eligibility

About

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 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. Aerosolized surfactant delivered during NIV is an innovative and promising concept for the treatment of RDS - 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. The objective of this proposal is to perform a single-center unblinded Phase II randomized clinical trial of aerosolized surfactant for the treatment of RDS in preterm neonates undergoing NIV. Funding Source - FDA-OOPD.

Enrollment: 159 patients

Sex: All

Ages: Under 24 hours old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Infants admitted to the NICU at Hutzel Women's Hospital (HWH)/Children's Hospital of Michigan (CHM)
2. Gestational age of 240/7-366/7 weeks
3. Postnatal age ≤ 24 hours
4. Clinical diagnosis of RDS based on (i) presence of at least two of the four classic symptoms (need of supplemental oxygen, tachypnea, intercostal retractions or grunting), and (ii) exclusion of other causes of respiratory failure and (iii) Clinician intent to administer surfactant if infant requires intubation
5. Respiratory support with NIV (CPAP or NIPPV or HFNC) with FiO2 ≥25% or PEEP ≥ 4 cmH20 or HFNC rate ≥ 2 LPM for ≤8 hours
6. Written informed consent from parent/guardian

Exclusion criteria

1. Previous receipt of surfactant
2. Infants with respiratory distress who are unstable and require immediate intubation
3. Active air leak syndrome (e.g. pneumothorax, pneumomediastinum)
4. Lethal congenital malformations; death anticipated within first 3 days of life; decision to withhold support
5. Serious abdominal, cardiac, airway or respiratory malformations including tracheal esophageal fistula, intestinal atresia, omphalocele, gastroschisis, pulmonary hypoplasia, or diaphragmatic hernia
6. Neuromuscular disorder resulting in respiratory compromise

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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159 participants in 4 patient groups

Dose Schedule I

Active Comparator group

Description:

Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:1

Treatment:

Drug: Surfactant

Dose Schedule II

Active Comparator group

Description:

Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:2

Treatment:

Drug: Surfactant

Dose Schedule III

Active Comparator group

Description:

Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:1

Treatment:

Drug: Surfactant

Dose Schedule IV

Active Comparator group

Description:

Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:2

Treatment:

Drug: Surfactant