Aerosolized Survanta in Neonatal Respiratory Distress Syndrome: Phase I/II Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 159
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events as a Measure of Safety and Feasibility
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 24 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Dose Schedule I
Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:1
干预措施: Surfactant (Drug)
Dose Schedule II
Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:2
干预措施: Surfactant (Drug)
Dose Schedule III
Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:1
干预措施: Surfactant (Drug)
Dose Schedule IV
Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:2
干预措施: Surfactant (Drug)
结局指标
主要结局
Number of Participants With Adverse Events as a Measure of Safety and Feasibility
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Need for Blood Transfusions(During initial hospital stay, expected <= 120 days)
- Changes in Surfactant Activity in Gastric Aspirates(During study intervention, expected maximum of approximately 8 hours)
- Blood Gas Parameters - pH(60±30 minutes after end of study intervention)
- 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)
- Duration of Supplemental Oxygen, Intensive Care, Hospital Stay(During initial hospital stay, expected <= 120 days)
- Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds(During initial hospital stay, expected 1st 2 weeks of life)
- Pulse Oximetry(60±30 minutes after end of study intervention)
- Cumulative Duration of Non-invasive and Invasive Ventilation(at discharge)
- Survival to Hospital Discharge(During initial hospital stay, expected <= 120 days)
- Blood Gas Parameters - pCO2(60±30 minutes after end of study intervention)
- Vital Signs - Heart Rate(60±30 minutes after end of study intervention)
- Vital Signs - Respiratory Rate(60±30 minutes after end of study intervention)
- Vital Signs - Systolic Blood Pressure(60±30 minutes after end of study intervention)
- 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)
- Morbidities Associated With Prematurity(During initial hospital stay, expected <= 120 days)
- Survival to Discharge Without Severe Morbidity(During initial hospital stay, expected <= 120 days)