1/2 percutaneous intervention versus observational trial of arterial ductus in lower gestational age infants (PIVOTAL)

1/2 经皮介入治疗与低胎龄儿动脉导管观察性试验 (PIVOTAL)

• 批准号: 10349765
• 负责人: Carl Backes
• 金额: $ 81.23万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-21 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10349765
• 关键词: Adoption; Age; Arteries; Belief; Birth; Blood Circulation; Brain; Brain Injuries; Caliber; Cardiopulmonary; Cardiovascular system; Caregivers; Caring; Catheters; Cessation of life; Chronic lung disease; Clinical; Complex; Consensus; Consent; Devices; Duct (organ) structure; Effectiveness; Equipoise; Ethnic Origin; Exposure to; Feasibility Studies; Gestational Age; Goals; Growth and Development function; Health Personnel; Heart; Human; Infant; Infant Health; Intensive Care; International; Intervention; Left; Legal patent; Link; Lung; Measures; Mechanical ventilation; Mediating; Medical; Medication Management; Mission; Morbidity - disease rate; Neonatal; Neonatal Intensive Care Units; Operative Surgical Procedures; Outcome; Output; Patent Ductus Arteriosus; Patient observation; Patient-Focused Outcomes; Patients; Peripheral; Pharmaceutical Preparations; Pregnancy; Premature Infant; Procedures; Process; Public Health; Pulmonary Hypertension; Pulmonary artery structure; Race; Randomized; Randomized Controlled Trials; Resort; Respiratory Disease; Risk; Safety; Severity of illness; Site; Techniques; Testing; Thoracic cavity structure; Uncertainty; United States Food and Drug Administration; United States National Institutes of Health; Veins; Ventilator; Ventricular; Vulnerable Populations; artery occlusion; base; efficacy study; experience; fetal; hemodynamics; improved; in utero; minimally invasive; mortality; neonatal outcome; neurodevelopment; novel; postnatal; prevent; randomized trial; recruit; respiratory; secondary outcome; sex; specific biomarkers; trial comparing

PROJECT SUMMARY/ABSTRACT Patent ductus arteriosus (PDA), the most common cardiovascular condition in preterm infants, is associated with mortality and harmful longer-term outcomes including chronic lung disease (CLD) and brain injury. Although treatment does not benefit all infants with PDA, likely due to spontaneous closure, treatment of some infants with symptomatic PDA is necessary. Medications are often used to close persistent preterm PDA in the initial four weeks postnatal, but fail to close the PDA in 1/3 of infants, in whom an intervention is the only remaining definitive closure option (failed pharmacological management). A treatment dilemma exists in the first postnatal month for the subset of infants with persistent, hemodynamically significant, and clinically symptomatic PDA (HSPDA) after postnatal week one following failed pharmacological management. Invasive, intrathoracic PDA surgery was tra- ditionally employed for infants with HSPDA, but associations between surgery and adverse neurodevelopment prompted widespread adoption of non-interventional, supportive treatment. This watchful-waiting approach avoids or delays procedure-related complications, but prolongs developing brain and lung exposure to PDA- related hemodynamics. Evidence is emerging that duration of HSPDA exposure is an important predictor of CLD and/or death. Percutaneous catheter-based closure (PPC) is a novel, minimally-invasive means of closing a HSPDA. A duct occluder (ADO-II AS) was recently approved (1/2019) by the US FDA for preterm infants weigh- ing ≥700 grams. However, the effectiveness of PPC in improving important neonatal outcomes relative to sup- portive (non-intervention) HSPDA management has never been evaluated via a randomized trial (RCT). The uncertainty is whether PPC should be performed early (days 7-30 postnatal) for all infants with HSDPA to prevent PDA-related complications or only rarely as a last resort following a prolonged trial of supportive management. The objective in this application is to determine if PPC improves cardiopulmonary and neurodevelopmental out- comes via a multicenter RCT comparing the two strategies. Aim 1 will determine the effect of PPC versus sup- portive treatment on ventilator-free days (VFDs) at 30 days post-randomization (non-survivors will be scored as having zero VFDs). Aim 2 will determine the effect of PPC versus supportive treatment on secondary cardiopul- monary, safety and neurodevelopmental outcomes. Aim 3 will evaluate whether neurodevelopment at 3-4 months corrected age is mediated by improved neurodevelopmental profiles at 34-36 weeks postmenstrual age. Aim 4 will evaluate potential effect modifiers of HDPSA (e.g., sex, race/ethnicity, gestational age, age at ran- domization) on VFDs and secondary outcomes. This trial will immediately advance the care of extremely preterm infants with HSPDA following failed medical management by identifying whether PPC or supportive treatment better improves cardiopulmonary and neurodevelopmental outcomes.

项目摘要/摘要 动脉导管未闭(PDA)是早产儿最常见的心血管疾病，与 死亡率和有害的长期后果，包括慢性肺病(CLD)和脑损伤。虽然 治疗并不是所有患有PDA的婴儿都受益，可能是由于自发闭合，治疗某些婴儿患有 有症状的动脉导管未闭是必要的。在最初的四个月里，药物经常被用来关闭持续性早产PDA 出生几周后，但1/3的婴儿未能关闭PDA，在这些婴儿中，干预是唯一确定的 关闭选项(失败的药理学管理)。在出生后的第一个月就存在着治疗的两难 持续性、血流动力学显着和临床症状PDA(HSPDA)的婴儿亚组 在药物治疗失败后的第一周。胸内侵入性动脉导管未闭手术 适用于患有HSPDA的婴儿，但手术与不良神经发育之间的关联 促使广泛采用非干预性、支持性治疗。这种警惕等待的方式 避免或推迟与手术相关的并发症，但延长发育中的大脑和肺暴露于PDA- 与血流动力学相关。越来越多的证据表明，接触HSPDA的时间是CLD的重要预测因素 和/或死亡。经皮导管封堵术(PPC)是一种新颖的微创封堵术。 HSPDA。美国FDA最近(2019年1月1日)批准了一种用于早产儿体重的导管封堵器(ADO-II AS)。 ING≥700g。然而，与超常妊娠相比，PPC在改善重要新生儿结局方面的有效性。 预防性(非干预)HSPDA治疗从未通过随机试验(RCT)进行评估。这个 不确定性是是否应该对所有患有HSDPA的婴儿早期(出生后7-30天)进行PPC，以防止 与PDA相关的并发症或在长期的支持性治疗试验后仅作为最后手段的情况很少发生。 这项应用的目的是确定PPC是否改善了心肺和神经发育。 通过多中心随机对照试验对这两种战略进行了比较。目标1将确定购买力平价与超级市场的效果 随机分组后30天无呼吸机天数(VFDs)的预防性治疗(未存活者评分为 具有零VFD)。目的2将确定PPC与支持治疗对继发性心力衰竭的影响。 肺、安全和神经发育结果。目标3将评估3-4岁的神经发育 月经后34-36周的神经发育状况改善是影响月经校正年龄的因素。 目标4将评估HDPSA的潜在影响因素(例如，性别、种族/民族、胎龄、跑步年龄- 对VFD和次要结果的控制)。这项试验将立即推进极早产的护理 通过确定PPC或支持性治疗失败而导致HSPDA的婴儿 更好地改善心肺和神经发育结果。