Trial Of Late SURFactant (TOLSURF) to Prevent BPD-Data Coordinating Center

试验晚期 SURFactant (TOLSURF) 预防 BPD-数据协调中心

• 批准号: 7564148
• 负责人: Dennis M Black
• 金额: $ 19.95万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7564148
• 关键词: 1 year old; 2 year old; Address; Adherence; Adverse effects; Age; Alveolar; Anti-Inflammatory Agents; Anti-inflammatory; Area; Aspirate substance; Asthma; Biological Assay; Biological Markers; Biometry; Birth; Blinded; Bronchopulmonary Dysplasia; California; Caring; Chronic lung disease; Clinic; Clinical; Clinical Trials; Clinical Trials Data Monitoring Committees; Combined Modality Therapy; Communication; DNA; Data; Data Analyses; Data Collection; Data Coordinating Center; Data Quality; Database Management Systems; Databases; Deterioration; Development; Documentation; Dose; Electronic Mail; Ensure; Environmental air flow; Epidemiology; Exposure to; Extremely Low Birth Weight Infant; Futility; Future; Genetic; Goals; Guidelines; Hospitalization; In Vitro; Infant; Inflammation; Inflammatory; Information Systems; Injury; Internet; Late Effects; Link; Lung; Lung Inflammation; Lung diseases; Manuals; Mechanical ventilation; Monitor; Morbidity - disease rate; Multiple Birth Offspring; National Heart, Lung, and Blood Institute; Operative Surgical Procedures; Outcome; Oxygen; Polymorphism Analysis; Pregnancy; Premature Infant; Prevalence; Prevention; Procedures; Property; Protocols documentation; Public Health; Publications; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactants; Quality Control; Randomized; Randomized Controlled Clinical Trials; Reporting; Research; Research Personnel; Safety; Sampling; San Francisco; Secondary to; Severities; Side; System; Telefacsimile; Time Study; Training; Treatment outcome; Universities; Ventilator; Volutrauma; Work; base; clinical research site; control trial; cost; cost effective; cytokine; data integrity; design; disability; experience; high standard; improved; inhaled nitric oxide; long term hospitalization; lung injury; mortality; novel therapeutic intervention; performance site; premature; prevent; primary outcome; repository; respiratory; response; secondary outcome; surfactant; web site

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）是极低的出生体重（ELBW <1000 g和<30周妊娠）婴儿的长期肺部残疾的主要原因。 BPD的病原体是多因素的，具有遗传成分，涉及肺损伤和炎症，其继发于用氧气和机械通气的较低发达的，未成熟的肺中的炎症。 ELBW婴儿中吸入的一氧化氮（INO）疗法在没有BPD的情况下会增加存活率，可改善肺癌的成本，直至1岁，具有成本效益，并且与短期或长期不良影响无关。但是，50％的INO治疗婴儿仍会发展为BPD。 ELBW婴儿在发育上缺乏肺表面活性剂，并在出生时接受替代表面活性剂治疗。我们观察到，通风婴儿的呼吸状况恶化与功能障碍表面活性剂和表面活性剂蛋白B含量低有关，并提出这些发作是通过增加肺部炎症和损伤的促进氧气和造成氧气和频率更大的氧气和ventilator诱导的Volutrauma的损伤来有助于BPD的发展。 INO治疗会瞬时提高表面活性剂功能，并且在治疗婴儿中正常的表面活性剂功能与改善的预后有关。我们建议，INO和晚期表面活性剂的结合将分别相互作用，以促进牙槽发育并减少持续的肺损伤。我们假设给接受INO的婴儿服用并需要在7-14 d时使用机械通气的婴儿的表面活性剂是安全的，并且在月经年龄（PMA）36 WK的情况下将增加生存率。 AIM 1评估了晚期剂量表面活性剂对在多中心随机，盲目对照试验中接受INO的通风ELBW婴儿中BPD的发生和严重程度的影响。在没有BPD 36周PMA的情况下，在没有BPD的主要结果中，证明500％的婴儿的功率为80％，两侧α为0.05，允许一个临时分析，7％的多个出生，并且停止效力或徒劳。次要结果包括在40周（术语），通风和住院期间排出呼吸道，以及1岁和2岁的肺部发病率和神经发育结果。 AIM 2评估晚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。表面活性剂是从系列气管抽吸物样品中分离出来的，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。气管抽吸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。将建立一个DNA存储库，以将来对与BPD相关的多态性和对治疗的反应进行分析。该申请描述了试验的临床协调中心。项目叙述性支气管肺发育不良（BPD）是一种慢性肺部疾病，发生在早产婴儿中，与长期昂贵的住院，长期肺部疾病以及神经发育异常和死亡率和神经发育异常和死亡率相关，并通过经验丰富的试验估计，在美国经验丰富的A型中估计，该临床效果将确定且效果，以确定效果。预防早产婴儿BPD的治疗方法。这项研究有可能减少慢性婴儿肺部疾病和哮喘，重要领域的重要领域，降低护理成本并改善早产婴儿的长期预后。