POET Study: A Randomized Multi-institutional Clinical Trial of Girls with Reflux

总体描述（由申请人提供）： 据估计，在美国每年有多达50，000名儿童在尿路感染后被新诊断为膀胱输尿管反流（VUR）。众所周知，在这些儿童中，VUR与复发性感染、肾盂肾炎和随后的肾瘢痕形成有关。这可能会导致高血压和肾功能不全以后在儿童或成年生活。然而，关于这些儿童的最佳治疗，或者说，他们是否都需要治疗，仍然存在很大的困惑。虽然似乎具有较高等级的扩张性反流（IV级和V级）的儿童具有最大的临床后遗症风险，但他们是少数患者。90%的儿童有I、II或III级反流。大多数患有低度反流的儿童在青春期前会超过他们的反流。因此，这些儿童的反流手术矫正不太常见。这些儿童的肾瘢痕形成率和尿路感染复发率也较低。虽然长期抗生素预防在预防泌尿系感染方面效果良好，但有人提出，在这一组中可能没有必要，因为瘢痕形成和复发性感染的发生率较低，伴有低度反流。最近，开发了一种新的反流微创治疗方法，FDA已批准一种称为“Deflux”的材料用于此目的。该材料通过膀胱镜注入输尿管口周围。由该填充剂引起的孔口构造的变化治愈了回流。由于其易于使用和低发病率的应用，它已被提议，这是作为初始治疗大多数儿童低度反流。使用Deflux的成功治疗可能需要长期监测，无论是否使用抗生素。因此，对于成千上万的反流儿童中的大多数，最佳治疗方法仍然未知。是否需要每天服用抗生素？它们可以在没有预防措施的情况下安全地观察吗？他们是否需要门诊膀胱镜检查？一项前瞻性随机研究，提出了回答这个问题的女孩，年龄1至5岁的II级或III级反流，诊断后尿路感染。三个主要治疗组为抗生素预防、观察（无预防）或内镜治疗（使用Deflux（ET））。测量的临床终点将是反复发热或非发热性尿路感染和肾瘢痕。

DESCRIPTION, OVERALL (provided by applicant): It is estimated that up to 50,000 children are newly diagnosed annually in the United States with vesicoureteral reflux (VUR) after a urinary tract infection. It is known that in some of these children, VUR is associated with recurrent infection, pyelonephritis and subsequent renal scarring. This can lead to hypertension and renal insufficiency later on in childhood or in adult life. There remains great confusion, however, regarding the optimal treatment of these children or indeed, if they all require treatment. While it appears that children with the higher grades of dilating reflux (grades IV & V) are at the greatest risk for clinical sequelae, they are a minority of patients. 90% of children have grades I, II or III reflux. The majority of children with low grade reflux will outgrow their reflux before adolescence. Surgical correction of reflux in these children is less commonly required, therefore. Rates of renal scarring and recurrent urinary tract infection are also lower in these children. While long term antibiotic prophylaxis works well in preventing urinary infection, it has been proposed that it may not be necessary in this group, since rates of scarring and recurrent infection are low with low grade reflux. Recently, a new minimally invasive treatment of reflux has been developed and a material known as "Deflux" has been approved by the FDA for this purpose. This material is injected via a cystoscope around the ureteral orifice. The change in configuration of the orifice caused by this bulking agent cures the reflux. Because of its ease of use and low morbidity of application, it has been proposed that this be employed as initial therapy in the majority of children with low grade reflux. Successful treatment with Deflux might render the need for long term surveillance, either on or off antibiotics unnecessary. The optimal treatment for the majority of the thousands of children with reflux, therefore, remains unknown. Do they simply require daily antibiotics? Can they be safely observed without prophylaxis? Do they require an ambulatory cystoscopic procedure? A prospective randomized study is proposed to answer this question in girls, aged one to five years with grades II or III reflux, diagnosed after a urinary tract infection. The three major treatment groups would be antibiotic prophylaxis, observation without prophylaxis, or endoscopic therapy with Deflux (ET). The clinical endpoints measured would be recurrent febrile or non-febrile urinary infections and renal scarrin