Twin-Twin Transfusion Syndrome Trial

双胎输血综合症试验

• 批准号: 6536423
• 负责人: TIMOTHY M CROMBLEHOLME
• 金额: $ 149.97万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-24 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6536423
• 关键词: amniotic fluid; body fluid balance therapy; clinical trials; echocardiography; embryo /fetus therapy; human pregnant subject; human subject; human therapy evaluation; magnetic resonance imaging; patient oriented research; photocoagulation therapy; placenta disorders; twin /multiplet; ultrasonography

DESCRIPTION (provided by applicant): The twin twin transfusion syndrome (TTTS) is the most common serious complication of monochorionic twin gestations, affecting between 4 and 35% of monochorionic twin pregnancies each year in the United States. The TTTS accounts for 17% of all perinatal mortality associated with twin gestations. Standard therapy in the United States has been limited to serial amnioreduction which appears to improve the overall outcome but has had little impact on the more severe end of the spectrum in TTTS. In addition, survivors of TTTS treated by serial amnioreduction have an 18 to 26% incidence of significant neurologic and cardiac morbidity. Selective fetoscopic laser photocoagulation of chorioangiopagus has emerged as an alternative treatment strategy in TTTS with comparable survival to serial amnioreduction in non-randomized, non- prospective clinical studies. The superiority of fetoscopic laser treatment of TTTS remains unproven. In our preliminary data we have observed enhanced survival with selective fetoscopic laser photocoagulation in pregnancies with TTTS that had already failed serial amnioreduction or rnicroseptostomy. We hypothesize that treatment of the underlying chorioangiopagus by selective fetoscopic laser photocoagulation will not only improve the survival of twins but will reduce the incidence of neurologic, cardiac, and developmental sequelae of TTTS. We propose to test this hypothesis by a prospective randomized multicenter trial to compare serial amnioreduction with selective fetoscopic laser photocoagulation. In. the course of this study we will address the following specific aims: 1) To demonstrate that selective laser photocoagulation of chorioangiopagus in severe tETS results in significantly improved survival of twins compared to aggressive serial amnioreduction therapy. Survival of recipients and donors, both within the same pregnancy and overall survival to 30 days after birth will be examined; 2) To demonstrate that selective laser photocoagulation results in significantly improved cardiac, neurologic, and developmental outcomes in survivors of severe TTTS compared to survivors treated by aggressive serial amnioreduction. This will be a multicenter prospective randomized clinical trial with patients randomized either to serial amnioreduction at one of 16 participating centers or selective fetoscopic laser surgery at one or two participating centers. The fetal echocardiograms will be reviewed in a blinded fashion to evaluate cardiac morbidity and response to treatment.. Similarly, prenatal ultrasounds, as well as ultrasounds and MRI s obtained in the first week of life and after 4 weeks, will be reviewed in a blinded fashion to evaluate the neurologic morbidity and distinguish prenatal from perinatal events. Long-term neurodevelopmental outcome will be evaluated by the NIGH]) Neonatal Network at 18 to 22 months of age. The overall goal of the study is to improve the outcomes of twins with TTTS by determining which treatment for TTTS has a better survival as well as cardiac, neurologic, and developmental outcome.

描述（由申请人提供）：双胞胎输血综合症 (TTTS) 是单绒毛膜双胞胎最常见的严重并发症 妊娠，影响 4% 至 35% 的单绒毛膜双胎妊娠 年在美国。 TTTS 占所有围产期的 17% 与双胞胎妊娠相关的死亡率。美国的标准治疗 各州仅限于连续羊膜减缩术，这似乎可以改善 总体结果，但对更严重的结局影响不大 TTTS 中的频谱。此外，TTTS 的幸存者还接受了系列治疗 羊膜减缩术有 18% 至 26% 的显着神经系统和 心脏发病率。选择性胎儿镜激光光凝术 绒毛膜血管造影已成为 TTTS 的替代治疗策略 与非随机、非连续羊膜减缩术的生存率相当 前瞻性临床研究。胎儿镜激光治疗的优越性 TTTS 尚未得到证实。在我们的初步数据中，我们观察到增强 妊娠期选择性胎儿镜激光光凝术的生存率 连续羊膜减缩术或微隔造口术已经失败的 TTTS。我们 假设通过选择性治疗潜在的绒毛膜血管病 胎儿镜激光光凝术不仅可以提高双胞胎的存活率 但会降低神经系统、心脏和发育障碍的发生率 TTTS的后遗症。我们建议通过前瞻性测试来检验这一假设 比较连续羊膜减缩术与选择性羊膜减缩术的随机多中心试验 胎儿镜激光光凝术。在。在本研究的过程中我们将 解决以下具体目标： 1) 证明选择性激光 严重 tETS 中绒毛膜血管造影的光凝效果显着 与积极的连续羊膜减缩术相比，双胞胎的生存率有所提高 治疗。受赠者和捐献者在同一妊娠期间的存活率 将检查出生后 30 天的总体存活率； 2）展示 选择性激光光凝可显着改善 严重 TTTS 幸存者的心脏、神经和发育结局 与接受积极连续羊膜减缩术治疗的幸存者相比。这将 是一项针对患者的多中心前瞻性随机临床试验 在 16 个参与中心之一随机接受连续羊膜减缩术 或在一两个参与中心进行选择性胎儿镜激光手术。这 胎儿超声心动图将以盲法进行审查以评估 心脏病发病率和对治疗的反应。同样，产前超声检查， 以及出生后第一周和出生后获得的超声波和 MRI 检查 4周，将以盲法方式进行审查以评估神经系统 发病率并区分产前和围产期事件。长期 神经发育结果将由 NIGH]) 新生儿网络进行评估 18至22个月大。研究的总体目标是提高 通过确定 TTTS 的哪种治疗方法有效果，可以了解 TTTS 双胞胎的结果 更好的生存以及心脏、神经和发育结果。