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.

项目概要/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结果，包括慢性肺病（CLD）和脑损伤。虽然 治疗并不能使所有患有 PDA 的婴儿受益，可能是由于自然闭合，对一些患有 PDA 的婴儿进行治疗 有症状的 PDA 是必要的。药物通常用于在最初的四个月内闭合持续性早产 PDA 产后几周，但 1/3 的婴儿未能闭合 PDA，其中干预是唯一有效的方法 关闭选项（药物治疗失败）。产后第一个月存在治疗困境 患有持续性、血流动力学显着且有临床症状的 PDA (HSPDA) 的婴儿亚群 药物治疗失败后的产后第一周。侵入性胸腔内 PDA 手术 通常用于患有 HSPDA 的婴儿，但手术与不良神经发育之间存在关联 促使人们广泛采用非介入性支持治疗。这种警惕等待的方式 避免或延迟手术相关并发症，但会延长发育中的大脑和肺部暴露于 PDA 的时间 相关血流动力学。越来越多的证据表明，HSPDA 暴露持续时间是慢性肺病 (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方法 HSPDA。美国 FDA 最近批准 (1/2019) 导管封堵器 (ADO-II AS) 用于早产儿体重 ≥700克。然而，PPC 在改善重要新生儿结局方面的有效性相对于支持 从未通过随机试验 (RCT) 评估过主动（非干预）HSPDA 管理。这 不确定的是是否应该对所有患有 HSDPA 的婴儿尽早（产后 7-30 天）进行 PPC 以预防 PDA 相关并发症或很少作为长期支持性治疗试验后的最后手段。 本申请的目的是确定 PPC 是否可以改善心肺和神经发育输出 通过比较这两种策略的多中心随机对照试验得出。目标 1 将确定 PPC 与 support 的效果 随机分组后 30 天无呼吸机日 (VFD) 的局部治疗（非幸存者将被评分为 具有零 VFD）。目标 2 将确定 PPC 与支持治疗对继发性心肺功能的影响 金钱、安全性和神经发育结果。目标 3 将评估 3-4 岁的神经发育是否 月校正年龄是通过经后 34-36 周神经发育状况的改善来调节的。 目标 4 将评估 HDPSA 的潜在影响因素（例如性别、种族/族裔、胎龄、随机年龄） domization）对VFD和次要结果的影响。该试验将立即推进极早产儿的护理 通过确定是 PPC 还是支持治疗，治疗失败后患有 HSPDA 的婴儿 更好地改善心肺和神经发育结果。