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.

项目总结/摘要 动脉导管未闭（PDA）是早产儿中最常见的心血管疾病， 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，可能是由于自发闭合， 有症状的PDA是必要的。药物通常用于关闭持续性早产PDA在最初的四个 但1/3的婴儿未能关闭PDA，其中干预是唯一剩下的决定性因素 关闭选项（药物治疗失败）。在出生后的第一个月， 持续性、血流动力学显著性和临床症状性PDA（HSPDA）婴儿亚组， 药物治疗失败后的产后第一周。有创性胸内PDA手术是一种跨- 传统上用于患有HSPDA的婴儿，但手术与不良神经发育之间存在联系 促使广泛采用非干预性支持性治疗。这种观察等待的方法 避免或延迟手术相关并发症，但避免发育中的大脑和肺部暴露于PDA- 相关的血液动力学。有证据表明HSPDA暴露持续时间是CLD的重要预测因素 或者死亡经皮导管闭合术（PPC）是一种新型的微创闭合方法， HSPDA。最近，美国FDA批准（2019年1月）一种用于早产儿的导管封堵器（ADO-II AS）， ≥700 g。然而，PPC在改善重要的新生儿结局方面的有效性相对于Sup. 部分（非干预）HSPDA管理从未通过随机试验（RCT）进行评估。的 不确定的是，是否应早期（出生后7-30天）对所有患有HSDPA的婴儿进行PPC，以预防 PDA相关并发症或仅作为支持性管理长期试验后的最后手段。 本申请的目的是确定PPC是否改善心肺和神经发育， 通过一项多中心随机对照试验比较了两种策略。目的1将确定PPC与sup- 随机化后30天无呼吸机日（VFD）的部分治疗（非存活者将评分为 具有零VFD）。目的2将确定PPC与支持性治疗对继发性心绞痛的影响。 安全性和神经发育结果。目标3将评估3-4岁时的神经发育是否 经后34-36周的神经发育状况改善介导了经后34-36周的矫正年龄。 目的4将评估HDPSA的潜在效应调节剂（例如，性别、人种/种族、胎龄、出生时年龄- domization）对VFD和次要结局的影响。这项试验将立即促进极早产儿的护理 通过确定PPC或支持性治疗失败后的HSPDA婴儿 更好地改善心肺和神经发育结果。