Aerosolized Surfactant in Neonatal RDS
- Conditions
- Respiratory Distress Syndrome, Newborn
- Interventions
- Drug: Surfactant
- Registration Number
- NCT02294630
- Lead Sponsor
- Sood, Beena G., MD, MS
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 159
- Infants admitted to the NICU at Hutzel Women's Hospital (HWH)/Children's Hospital of Michigan (CHM)
- Gestational age of 240/7-366/7 weeks
- Postnatal age ≤ 24 hours
- 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
- Respiratory support with NIV (CPAP or NIPPV or HFNC) with FiO2 ≥25% or PEEP ≥ 4 cmH20 or HFNC rate ≥ 2 LPM for ≤8 hours
- Written informed consent from parent/guardian
- Previous receipt of surfactant
- Infants with respiratory distress who are unstable and require immediate intubation
- Active air leak syndrome (e.g. pneumothorax, pneumomediastinum)
- Lethal congenital malformations; death anticipated within first 3 days of life; decision to withhold support
- Serious abdominal, cardiac, airway or respiratory malformations including tracheal esophageal fistula, intestinal atresia, omphalocele, gastroschisis, pulmonary hypoplasia, or diaphragmatic hernia
- Neuromuscular disorder resulting in respiratory compromise
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Schedule I Surfactant Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:1 Dose Schedule II Surfactant Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:2 Dose Schedule III Surfactant Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:1 Dose Schedule IV Surfactant Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:2
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events as a Measure of Safety and Feasibility During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours Since surfactant reflux is typically considered to be one of the most likely adverse events associated with the intervention, it was planned to report the number of participants specifically with surfactant reflux for this Outcome Measure
Patient Status as Evaluated by Dose Level 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. Optimal dosing schedule was determined by preliminary evidence of efficacy (Need for intubation within 72 hours), lack of adverse effects, and overall infant comfort as assessed by bedside clinical caregivers.
Short Term Efficacy as Assessed by Need for Intubation Within 72 hours of study intervention It will be suggested that infants be intubated and receive MV if they met 2 or more of 5 failure criteria: i). worsening clinical signs of respiratory distress (increasing tachypnea; expiratory grunting; intercostal, subcostal, and/or sternal recession); ii). apnea treated with positive pressure ventilation (PPV) by mask on 2 or more occasions in 1 hour; iii). FIO2 \>0.5 to maintain pulse oxygen saturations 90%-95% for \>30 minutes; iv). pH \<7.2 on 2 arterial or capillary blood gases taken \>30 minutes apart; and v). partial pressure of CO2 (PCO2) of \>65 mm Hg on 2 CBG/ABGs taken 30 minutes apart.
- Secondary Outcome Measures
Name Time Method Need for Blood Transfusions During initial hospital stay, expected <= 120 days Number of infants requiring blood transfusions
Changes in Surfactant Activity in Gastric Aspirates During study intervention, expected maximum of approximately 8 hours Concentration of major surfactant lipid (PC 16:0/16:0)
Blood Gas Parameters - pH 60±30 minutes after end of study intervention Blood gas pH
Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention During and within 6 hours after end of study intervention, expected maximum of approximately 14 hours Changes in cerebral oxygenation from baseline as evaluated at end of study intervention
Duration of Supplemental Oxygen, Intensive Care, Hospital Stay During initial hospital stay, expected <= 120 days Duration of supplemental oxygen, and hospital stay
Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds During initial hospital stay, expected 1st 2 weeks of life Age at start of feeds, and age at full enteral feeds presented in days
Pulse Oximetry 60±30 minutes after end of study intervention Transcutaneous Pulse oximetry
Cumulative Duration of Non-invasive and Invasive Ventilation at discharge Cumulative duration of non-invasive and invasive ventilation at discharge
Survival to Hospital Discharge During initial hospital stay, expected <= 120 days Survival to hospital discharge
Blood Gas Parameters - pCO2 60±30 minutes after end of study intervention Blood gas pCO2.
Vital Signs - Heart Rate 60±30 minutes after end of study intervention Vital signs included heart rate, respiratory rate and systolic blood pressure
Vital Signs - Respiratory Rate 60±30 minutes after end of study intervention Vital signs included heart rate, respiratory rate and systolic blood pressure
Vital Signs - Systolic Blood Pressure 60±30 minutes after end of study intervention Systolic blood pressure
Number of Doses of Surfactant - Aerosolized & Intratracheal Within 72 hours of study intervention Pneumothorax, Pneumomediastinum or Other Air Leak Within 72 hours of study intervention Growth Parameters At 7 days, 28 days, 36 weeks corrected GA and discharge Weight at discharge
Morbidities Associated With Prematurity During initial hospital stay, expected <= 120 days Grade III \& IV IVH PDA requiring ligation ROP treated with Laser Surgical NEC BPD
Survival to Discharge Without Severe Morbidity During initial hospital stay, expected <= 120 days Survival to discharge without severe BPD, severe IVH, surgical NEC or ROP treated with Laser
Trial Locations
- Locations (1)
Hutzel Women's Hospital
🇺🇸Detroit, Michigan, United States