Trial of Late SURFactant (TOLSURF) to Prevent BPD - Clinical Coord Ctr

晚期 SURFactant (TOLSURF) 预防 BPD 的试验 - Clinical Coord Ctr

基本信息

项目摘要

DESCRIPTION (provided by applicant): Bronchopulmonary dysplasia (BPD) is a major and costly cause of long-term pulmonary disability in extremely low birth weight (ELBW <1000 g and <30 weeks gestation) infants. The pathogensis of BPD is multi-factorial, has a genetic component, and involves lung injury and inflammation secondary to treatment with oxygen and mechanical ventilation in an underdeveloped, immature lung. Inhaled Nitric Oxide (iNO) therapy in ELBW infants increases survival without BPD, improves pulmonary outcome through 1 year of age, is cost effective, and is not associated with short- or long-term adverse effects. However 50% of iNO-treated infants still develop BPD. ELBW infants are developmentally deficient in pulmonary surfactant and receive replacement surfactant treatment at birth. We observed that deteriorations in respiratory status in ventilated infants are associated with dysfunctional surfactant and low content of surfactant proteins B and C, and propose that these episodes contribute to development of BPD by increasing lung inflammation and injury secondary to greater exposure to oxygen and ventilator-induced volutrauma. INO therapy transiently improves surfactant function, and normal surfactant function in treated infants is associated with improved outcome. We propose that the combination of iNO and late surfactant will interact to promote alveolar development and reduce continuing lung injury, respectively. We hypothesize that late doses of surfactant administered to infants receiving iNO and requiring mechanical ventilation at 7-14 d of age is safe and will increase survival without BPD at 36 wk post menstrual age (PMA). Aim 1 assesses the effect of late doses of surfactant on the occurrence and severity of BPD in ventilated ELBW infants who are receiving iNO in a multi-center randomized, blinded, controlled trial. Demonstrating an increase from 50 to 62.5% in the primary outcome of survival without BPD at 36 wk PMA requires 500 infants to have 80% power and a two-sided alpha of 0.05, allowing for one interim analysis, 7% multiple births, and stopping for either efficacy or futility. Secondary outcomes include discharge off respiratory support at 40 wk (term), duration of ventilation and hospitalization, and pulmonary morbidity and neurodevelopmental outcome at 1 and 2 years of age. Aim 2 assesses effects of late surfactant treatment on surfactant status and lung inflammatory biomarkers. Surfactant is isolated from serial tracheal aspirate samples to determine the association of in vitro surfactant properties with respiratory status, surfactant treatment, and outcome. Assays of tracheal aspirate cytokines will examine safety and potential anti- inflammatory effects of combined treatment. A DNA repository will be established for future analysis of polymorphisms associated with BPD and response to treatment. This application describes the Clinical Coordinating Center for the trial. Project Narrative Bronchopulmonary Dysplasia (BPD) is the chronic lung disease that occurs in premature infants and is associated with prolonged and costly hospitalization, long-term lung diseases, and neurodevelopmental abnormalities and mortality, with a prevalence estimated at 30,000 cases/year in the U.S. This clinical trial by experienced investigators utilizing an established trial network will determine the safety and efficacy of a new therapeutic approach for prevention of BPD in premature infants. This research has potential to decrease chronic infant lung disease and asthma, important areas of public health, reduce cost of care, and improve long-term outcome for premature infants.
描述(由申请人提供): 支气管肺发育不良 (BPD) 是极低出生体重(ELBW <1000 g 且妊娠 <30 周)婴儿长期肺部残疾的主要原因,且代价高昂。 BPD 的发病机制是多因素的,具有遗传因素,并涉及在不发达、不成熟的肺部接受氧气和机械通气治疗后继发的肺损伤和炎症。 ELBW 婴儿吸入一氧化氮 (iNO) 疗法可提高无 BPD 的生存率,改善 1 岁之前的肺部结局,具有成本效益,并且不会产生短期或长期不良反应。然而,50% 接受 iNO 治疗的婴儿仍然患有 BPD。 ELBW 婴儿在发育上缺乏肺表面活性剂,因此在出生时接受表面活性剂替代治疗。我们观察到,通气婴儿呼吸状态的恶化与表面活性剂功能失调以及表面活性剂蛋白 B 和 C 含量低有关,并提出这些情况通过增加肺部炎症和继发于更多氧气暴露和呼吸机引起的体积伤而导致的损伤,从而导致 BPD 的发展。 INO 疗法可暂时改善表面活性剂功能,并且治疗婴儿中表面活性剂功能正常与改善的结果相关。我们认为 iNO 和晚期表面活性剂的组合将相互作用,分别促进肺泡发育和减少持续性肺损伤。我们假设,对接受 iNO 并在 7-14 天需要机械通气的婴儿给予后期表面活性剂剂量是安全的,并且会增加经期后 36 周 (PMA) 时无 BPD 的存活率。目标 1 在一项多中心随机、盲法、对照试验中评估晚期剂量的表面活性剂对接受 iNO 的通气 ELBW 婴儿 BPD 的发生和严重程度的影响。证明 PMA 36 周时无 BPD 的主要生存结果从 50% 增加到 62.5%,需要 500 名婴儿拥有 80% 的功效和 0.05 的两侧 alpha,允许进行一次中期分析,7% 的多胞胎,并因有效或无效而停止。次要结局包括 40 周(足月)时脱离呼吸支持、通气和住院时间以及 1 岁和 2 岁时的肺部发病率和神经发育结果。目标 2 评估后期表面活性剂治疗对表面活性剂状态和肺部炎症生物标志物的影响。从连续气管吸出物样品中分离表面活性剂,以确定体外表面活性剂特性与呼吸状态、表面活性剂治疗和结果的关联。气管吸出细胞因子的测定将检查联合治疗的安全性和潜在的抗炎作用。将建立 DNA 存储库,用于未来分析与 BPD 相关的多态性和治疗反应。该申请描述了试验的临床协调中心。项目叙事支气管肺发育不良 (BPD) 是一种发生在早产儿中的慢性肺部疾病,与长期且昂贵的住院治疗、长期肺部疾病以及神经发育异常和死亡有关,在美国,患病率估计为每年 30,000 例。这项临床试验由经验丰富的研究人员利用现有的试验网络进行,将确定一种新药物的安全性和有效性。 预防早产儿 BPD 的治疗方法。这项研究有可能减少慢性婴儿肺病和哮喘(公共卫生的重要领域)、降低护理成本并改善早产儿的长期结果。

项目成果

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Roberta Anderson Ballard其他文献

Roberta Anderson Ballard的其他文献

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{{ truncateString('Roberta Anderson Ballard', 18)}}的其他基金

Trial of Late SURFactant (TOLSURF) to Prevent BPD - Clinical Coord Ctr
晚期 SURFactant (TOLSURF) 预防 BPD 的试验 - Clinical Coord Ctr
  • 批准号:
    7928129
  • 财政年份:
    2009
  • 资助金额:
    $ 178.74万
  • 项目类别:
Trial of Late SURFactant (TOLSURF) to Prevent BPD - Clinical Coord Ctr
晚期 SURFactant (TOLSURF) 预防 BPD 的试验 - Clinical Coord Ctr
  • 批准号:
    8119622
  • 财政年份:
    2009
  • 资助金额:
    $ 178.74万
  • 项目类别:
Trial of Late SURFactant (TOLSURF) to Prevent BPD - Clinical Coord Ctr
晚期 SURFactant (TOLSURF) 预防 BPD 的试验 - Clinical Coord Ctr
  • 批准号:
    8520379
  • 财政年份:
    2009
  • 资助金额:
    $ 178.74万
  • 项目类别:
Trial of Late SURFactant (TOLSURF) to Prevent BPD - Clinical Coord Ctr
晚期 SURFactant (TOLSURF) 预防 BPD 的试验 - Clinical Coord Ctr
  • 批准号:
    8309224
  • 财政年份:
    2009
  • 资助金额:
    $ 178.74万
  • 项目类别:
LOW DOSE INO IN CHRONIC LUNG DISEASE IN PRETERM INFANT
低剂量 INO 治疗早产儿慢性肺病
  • 批准号:
    7207786
  • 财政年份:
    2005
  • 资助金额:
    $ 178.74万
  • 项目类别:
LOW DOSE INO IN CHRONIC LUNG DISEASE IN PRETERM INFANT
低剂量 INO 治疗早产儿慢性肺病
  • 批准号:
    7207684
  • 财政年份:
    2005
  • 资助金额:
    $ 178.74万
  • 项目类别:
PATHOBIOLOGY OF BRONCHOPULMONARY DYSPLASIA
支气管肺发育不良的病理学
  • 批准号:
    7207674
  • 财政年份:
    2005
  • 资助金额:
    $ 178.74万
  • 项目类别:
PATHOBIOLOGY OF BRONCHOPULMONARY DYSPLASIA
支气管肺发育不良的病理学
  • 批准号:
    7207784
  • 财政年份:
    2005
  • 资助金额:
    $ 178.74万
  • 项目类别:
Low dose INO in chronic lung disease in preterm infant
低剂量 INO 治疗早产儿慢性肺病
  • 批准号:
    7041808
  • 财政年份:
    2004
  • 资助金额:
    $ 178.74万
  • 项目类别:
Pathobiology of bronchopulmonary dysplasia
支气管肺发育不良的病理学
  • 批准号:
    7041889
  • 财政年份:
    2004
  • 资助金额:
    $ 178.74万
  • 项目类别:

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