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 专利导管动脉（PDA）是早产儿中最常见的心血管疾病，与 死亡率和有害的长期结局，包括慢性肺病（CLD）和脑损伤。虽然 治疗并不能使所有PDA婴儿受益，这可能是由于赞助者，对某些婴儿的治疗 有症状的PDA是必要的。药物通常用于关闭最初四个的持久性早产PDA 产后几周，但无法关闭1/3的婴儿的PDA，其中干预是唯一剩下的确定性 关闭选项（药物管理失败）。在出生后的第一个月存在治疗困境 具有持续性，血液动力学意义和临床上有症状的PDA（HSPDA）的婴儿的子集 产后第一周的药物管理失败。侵入性的胸膜内PDA手术进行了 针对患有HSPDA的婴儿的双期就业，但是手术与不良神经发育之间的关联 促使宽度采用非差异，支持性治疗。这种警惕的等待方法 避免或延迟程序相关的并发症，但会延长大脑的发展并暴露于PDA- 相关的血液动力学。有证据表明，HSPDA暴露持续时间是CLD的重要预测指标 和/或死亡。基于经皮导管的闭合（PPC）是一种新颖的，最小的侵入性手段 HSPDA。美国FDA最近批准了一种封闭式（ADO-II AS）（1/2019），以实现早产儿的体重 - ≥700克。但是，PPC在改善重要的新生儿结果方面的有效性 从未通过随机试验（RCT）评估Portive（非干预）HSPDA管理。这 不确定性是所有患有HSDPA婴儿的PPC是否应提早进行PPC（第7-30天）以防止 长期对支持管理的试验，与PDA相关的并发症或最少作为最后的度假胜地。 该应用程序的目的是确定PPC是否改善了心肺和神经发育外 AIM 1将确定PPC与SUP-的影响 随机化后30天对无呼吸机（VFD）进行验证治疗（非幸存者将评分为 零VFD）。 AIM 2将确定PPC与受支持的治疗对继发性心脏的影响 Monary，安全性和神经发育结果。 AIM 3将评估神经发育是否在3-4 校正年龄在月经后34-36周时改善神经发育特征的介导。 AIM 4将评估HDPSA的潜在效应修饰符（例如，性别，种族/种族，胎龄，年龄在RAN- VFD和次要结果的剂量）。该审判将立即提高极端早产的照顾 通过确定PPC或支持治疗方法，患有HSPDA的婴儿在医疗管理失败后 更好地改善了心肺和神经发育结果。