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

雾化 Survanta 治疗新生儿呼吸窘迫综合征的 1/2 期研究

• 批准号: 9099512
• 负责人: BEENA G. SOOD
• 金额: $ 39.99万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9099512
• 关键词: Phase; Study; Aerosolized; Survanta; Treatment

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.

描述（由申请人提供）： 由表面活性物质缺乏引起的呼吸窘迫综合征（RDS）是早产儿死亡和发病的主要原因。气管内滴注是唯一批准的表面活性剂递送方式，需要气管内插管和机械通气，伴随着风险。减少插管和机械通气（MV）需求的干预措施，如无创通气（NIV），包括鼻持续气道正压通气、高流量鼻插管或鼻间歇指令通气，越来越多地用于RDS早产儿的初始呼吸支持，以改善结局。 然而，NIV的使用不仅避免了插管和机械通气的需要，而且还延迟了表面活性剂的施用。因此，雾化表面活性剂在NIV期间递送预计是一种创新的和有前途的概念，用于治疗RDS，保留早期表面活性剂与肺泡复张的优点，同时避免插管和机械通气的风险。 研究者的总体假设是，在接受NIV的早产儿中使用雾化表面活性剂治疗RDS是安全可行的，并且将导致氧合和通气的短期改善，从而导致重症监护支持的需求减少，早产儿并发症，住院时间和医疗保健费用减少。本提案的目的是进行一项单中心、非盲、I/II期、随机临床试验，研究雾化表面活性剂治疗接受NIV的早产儿RDS。研究者将通过解决以下具体目标来实现这一目标： 具体目标1：评价两种获批用于新生儿的雾化器（MiniHeart Lo-Flo jet和AeroNeb Solo振动网孔雾化器）产生的雾化表面活性剂的安全性和可行性。将通过监测心肺参数、NIV回路堵塞、鼻创伤评分和脑氧合来评价安全性。将根据婴儿和临床护理人员的耐受性评估可行性。 具体目标2：确定雾化表面活性剂治疗NIV早产儿RDS的最佳稀释度和剂量。将婴儿随机分配至2个剂量和2个雾化表面活性剂稀释液组，形成4个给药方案。 具体目标3：通过评估出生后前72小时内插管和MV的需求，评价雾化表面活性剂的短期疗效。还将评估气雾剂给药的有效性 通过在雾化表面活性剂后胃吸出物中表面活性剂活性的变化。其他次要疗效指标包括呼吸严重程度评分、动脉导管未闭诊断、输血需求、出生后生长、呼吸支持持续时间、住院时间、早产并发症和死亡发生率。