Renal Anhydramnios Fetal Therapy (RAFT) Trial

肾性羊水不足胎儿治疗 (RAFT) 试验

• 批准号: 10378754
• 负责人: Meredith Ann Atkinson
• 金额: $ 65.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10378754
• 关键词: Abruptio Placentae; Address; Affect; American; Amniocentesis; Amniotic Fluid; Amniotic Fluid Embolism; Bilateral; Biological Markers; Birth; Case Study; Cessation of life; Child; Childhood; Chronic; Clinical; Data; Data Coordinating Center; Decision Making; Diagnosis; Dialysis procedure; Disease; Early Diagnosis; Educational workshop; Eligibility Determination; Equipment and supply inventories; Exclusion Criteria; Family; Feasibility Studies; Fetal Diseases; Fetal Lung; Fetal safety; Fetus; First Pregnancy Trimester; Goals; Growth; Head; Hemodialysis; Hemorrhage; Hospitals; Impairment; Infant; Infusion procedures; Institutional Review Boards; Intervention; Kidney; Kidney Failure; Kidney Transplantation; Knowledge; Letters; Light; Lung; Magnetic Resonance Imaging; Maternal complication; Measurement; Measures; Modeling; Multi-Institutional Clinical Trial; National Institute of Child Health and Human Development; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Neonatal; Outcome; Oxygen; Parents; Patients; Peritoneal Dialysis; Pregnancy; Premature Birth; Premature Labor; Prospective Studies; Proteomics; Protocols documentation; Publishing; Pulmonary artery structure; Quality of life; Radiology Specialty; Renal Tissue; Renal function; Reporting; Respiratory Failure; Respiratory physiology; Safety; Saline; Secondary to; Site; Stress; Survivors; Techniques; Testing; Therapy trial; Toddler; Transplantation; Treatment Efficacy; United States; Urinary tract; Urine; Uterine Rupture; Woman; Work; base; clinical practice; cohort; congenital anomalies of the kidney; early onset; early pregnancy; efficacy study; experience; fetal; health goals; improved; in utero; inclusion criteria; innovation; intraamniotic infection; lipidomics; living kidney donor; lung development; lung preservation; lung volume; maternal safety; neonatal period; neonate; novel; pilot trial; post-transplant; postnatal; prenatal; prenatal therapy; preterm premature rupture of membranes; prospective; pulmonary function; pulmonary hypoplasia; renal agenesis; safety and feasibility; safety study; treatment strategy; ultrasound

Summary The goal of this proposal is to evaluate the safety, feasibility and efficacy of serial amnioinfusions, a novel fetal therapy for early pregnancy renal anhydramios (EPRA). EPRA occurs in more than 1 in 2000 pregnancies and affects 1500 families in the U.S annually. EPRA has previously been considered universally fatal due to its associated pulmonary hypoplasia and neonatal respiratory failure. More recently, preliminary data from case reports have demonstrated an association between serial amnioinfusion therapy and short-term postnatal survival in EPRA fetuses, with excellent respiratory function in the neonatal period. Furthermore, long-term survival has been observed in a few cases, largely due to advances in neonatal dialysis and the advent of safe living donor kidney transplantation in toddlers. Serial amnioinfusions for the management of EPRA have been implemented in clinical practice, but no systematic and prospective study evaluating this treatment has occurred. Therefore, there is a lack of generalizable knowledge about the maternal/fetal safety, feasibility and short- and long-term clinical outcomes of this intervention. This proposal to study Renal Anhydramnios Fetal Therapy (RAFT) consists of a multi-center, non-randomized prospective trial to address the following specific aims: (1) To determine the maternal and fetal safety and feasibility of serial amnioinfusions for EPRA (2) To examine the short-term efficacy of RAFT and (3) To determine the long-term efficacy of RAFT on survival and quality of life. A consortium of 8 advanced fetal centers will operate under a single institutional review board with one protocol that has strict inclusion and exclusion criteria. Each center has been selected based on long experience and expertise in advanced fetal therapy and neonatal dialysis. This pilot trial will also seek to elucidate the mechanism of RAFT by capturing radiologic and amniotic fluid biomarkers during therapy. Furthermore, it will permit the first prospective analysis of the in utero natural history of EPRA by rigorously tracking patients who do not terminate their EPRA pregnancy but do not wish to undergo serial amnioinfusions. The RAFT trial not only has the potential to improve our understanding of the effect of serial amnioinfusions on lung growth in EPRA but also on other fetal diseases that impair lung function. Furthermore, serial amnioinfusions in EPRA pregnancies and serial acquisition of amniotic fluid biomarkers along with assessment of radiologic biomarkers may shed new light on the mechanisms of normal lung development. Most importantly, this trial will provide crucial data to assist families in making decisions about fetal therapy for fetuses affected by EPRA, making incremental progress toward the goal of health from birth for all children.

概括 该提案的目的是评估连续羊膜的安全性，可行性和功效，这是一种新颖的胎儿 怀孕早期肾脏藻类（EPRA）的治疗。 EPRA发生在2000年的怀孕中超过1例，并且 每年在美国影响1500个家庭。 EPRA以前由于其普遍致命而被认为是致命的 相关的肺动脉症和新生儿呼吸衰竭。最近，来自案例的初步数据 报告表明，串行羊膜灌注疗法与短期产后之间存在关联 EPRA胎儿的存活率，在新生儿时期具有出色的呼吸功能。此外，长期 在少数情况下已经观察到生存，这主要是由于新生儿透析的进步和安全的出现 幼儿中的活供体肾脏移植。 EPRA管理的串行羊膜吸收率已经 在临床实践中实施，但没有评估这种治疗方法的系统和前瞻性研究 发生。因此，缺乏有关母亲/胎儿安全性，可行性和 这种干预的短期和长期临床结果。这项研究肾脏藻类胎儿的建议 治疗（RAFT）由一个多中心的非随机前瞻性试验组成，以解决以下特定 目的：（1）确定ePRA连续羊膜症的母亲和胎儿安全性以及可行性 （2）检查筏的短期疗效和（3）确定筏的长期疗效 生存和生活质量。由8个高级胎儿中心组成的财团将在一个机构下运营 审核委员会具有一项具有严格包含和排除标准的协议。每个中心都被选中 基于晚期胎儿疗法和新生儿透析的长期经验和专业知识。该试点审判也将 寻求通过在治疗过程中捕获放射线和羊水生物标志物来阐明筏的机制。 此外，它将通过严格地对EPRA的子宫内自然史进行首次前瞻性分析 跟踪未终止EPRA妊娠但不希望经历系列羊膜症的患者。 RAFT试验不仅有潜力提高我们对连续羊膜症对的影响的理解 EPRA的肺部生长以及其他损害肺功能的胎儿疾病。此外，系列 EPRA妊娠和羊水生物标志物的串行获取以及评估 放射生物标志物可能对正常肺发育的机制开发新的启示。最多 重要的是，该试验将提供关键数据，以帮助家庭做出有关胎儿治疗的决定 受EPRA影响的胎儿，从出生到所有儿童的健康目标方面取得了渐进的进步。