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: 9316340
• 负责人: BEENA G. SOOD
• 金额: $ 20.37万
• 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 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9316340
• 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)： 肺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。气管内滴注是唯一被批准的表面活性物质输送方式，需要气管内插管和机械通气，但伴随着风险。减少插管和机械通气(MV)需求的干预措施，如无创呼吸机(NIV)，包括鼻腔持续正压、高流量鼻管或鼻间歇性指令通气，正越来越多地被用于早产儿RDS的初始呼吸支持，以改善预后。然而，NIV的使用不仅避免了插管和机械通气的需要，而且还推迟了表面活性物质的使用。因此，在NIV期间提供的雾化表面活性物质有望成为治疗RDS的一种创新和有前途的概念，它保留了早期表面活性物质与肺泡再充盈的优点，同时避免了插管和机械通气的风险。 研究人员的总体假设是，在接受NIV治疗的早产儿中使用雾化表面活性物质治疗RDS是安全可行的，并将在短期内改善氧合和换气，从而减少对重症监护支持的需求、早产并发症、住院时间和医疗费用。这项建议的目的是进行一项单中心、非盲法、1/2期的随机临床试验，雾化表面活性物质治疗接受NIV治疗的早产儿RDS。调查员将通过处理以下具体目标来实现这一目标： 具体目标1：评估由两种获准用于新生儿的雾化器产生的雾化表面活性剂的安全性和可行性，这两种雾化器分别是微型心脏Lo-Flo喷嘴和AeroNeb Solo振动筛网喷雾器。安全性将通过监测心肺参数、NIV回路阻塞、鼻创伤评分和脑氧合情况进行评估。可行性将由婴儿和临床护理人员在耐受性方面进行评估。 具体目标2：确定雾化表面活性物质治疗NIV治疗早产儿RDS的最佳稀释度和剂量。婴儿将被随机分成两种剂量和两种稀释的雾化表面活性物质，从而形成四种给药时间表。 具体目标3：评估雾化表面活性物质的短期疗效，通过在生命的最初72小时内的插管需要和机械通气来评估。还将评估气雾剂的效果。 通过雾化吸入表面活性物质后胃液中表面活性物质的变化。其他次要疗效指标包括呼吸严重程度评分、动脉导管未闭的诊断、是否需要输血、出生后发育、呼吸支持时间、住院时间、早产并发症发生率和死亡。