Clinical trial NCT02294630: Aerosolized Surfactant in Neonatal RDS
Official title: Aerosolized Survanta in Neonatal Respiratory Distress Syndrome: Phase I/II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Respiratory Distress Syndrome, Newborn
Lead sponsor: Sood, Beena G., MD, MS
Sponsor class: INDIV
First posted: 2014-11-19
Enrollment: 159
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Feasibility
timeFrame: During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours
measure: Patient Status as Evaluated by Dose Level
timeFrame: During study drug administration, expected maximum of approximately 8 hours for adverse effects and infant comfort; need for intubation was assessed within 72 hours of study intervention.
measure: Short Term Efficacy as Assessed by Need for Intubation
timeFrame: Within 72 hours of study intervention
Secondary outcomes:
measure: Blood Gas Parameters - pH
timeFrame: 60±30 minutes after end of study intervention
measure: Blood Gas Parameters - pCO2
timeFrame: 60±30 minutes after end of study intervention
measure: Pulse Oximetry
timeFrame: 60±30 minutes after end of study intervention
measure: Vital Signs - Heart Rate
timeFrame: 60±30 minutes after end of study intervention
measure: Vital Signs - Respiratory Rate
timeFrame: 60±30 minutes after end of study intervention
measure: Vital Signs - Systolic Blood Pressure
timeFrame: 60±30 minutes after end of study intervention
measure: Number of Doses of Surfactant - Aerosolized & Intratracheal
timeFrame: Within 72 hours of study intervention
measure: Pneumothorax, Pneumomediastinum or Other Air Leak
timeFrame: Within 72 hours of study intervention
measure: Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention
timeFrame: During and within 6 hours after end of study intervention, expected maximum of approximately 14 hours
measure: Changes in Surfactant Activity in Gastric Aspirates
timeFrame: During study intervention, expected maximum of approximately 8 hours
measure: Cumulative Duration of Non-invasive and Invasive Ventilation
timeFrame: at discharge
measure: Duration of Supplemental Oxygen, Intensive Care, Hospital Stay
timeFrame: During initial hospital stay, expected <= 120 days
measure: Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds
timeFrame: During initial hospital stay, expected 1st 2 weeks of life
measure: Need for Blood Transfusions
timeFrame: During initial hospital stay, expected <= 120 days
measure: Growth Parameters
timeFrame: At 7 days, 28 days, 36 weeks corrected GA and discharge
measure: Morbidities Associated With Prematurity
timeFrame: During initial hospital stay, expected <= 120 days
measure: Survival to Hospital Discharge
timeFrame: During initial hospital stay, expected <= 120 days
measure: Survival to Discharge Without Severe Morbidity
timeFrame: During initial hospital stay, expected <= 120 days
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Hutzel Women's Hospital
state: Michigan
Study officials:
affiliation: Wayne State University
name: Beena G. Sood, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sood BG, Cortez J, Kolli M, Sharma A, Delaney-Black V, Chen X. Aerosolized surfactant in neonatal respiratory distress syndrome: Phase I study. Early Hum Dev. 2019 Jul;134:19-25. doi: 10.1016/j.earlhumdev.2019.05.005. Epub 2019 May 20.
citation: Sood BG, Thomas R, Delaney-Black V, Xin Y, Sharma A, Chen X. Aerosolized Beractant in neonatal respiratory distress syndrome: A randomized fixed-dose parallel-arm phase II trial. Pulm Pharmacol Ther. 2021 Feb;66:101986. doi: 10.1016/j.pupt.2020.101986. Epub 2020 Dec 16.