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，美国每年有多达5万名儿童在尿路感染后新诊断为膀胱输尿管返流(VUR)。众所周知，在其中一些儿童中，输尿管反流与反复感染、肾盂肾炎和随后的肾疤痕形成有关。这可能会在儿童时期或成年后导致高血压和肾功能不全。然而，对于这些儿童的最佳治疗，或者实际上，他们是否都需要治疗，仍然存在很大的困惑。虽然扩张性反流级别较高(IV和V级)的儿童似乎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级、II级或III级反流。大多数患有低度反流的儿童在青春期之前就会长大，不再反流。因此，手术矫正这些儿童的反流不是很常见。这些儿童的肾脏疤痕和反复尿路感染的发生率也较低。虽然长期的抗生素预防在预防尿路感染方面效果很好，但有人认为在这一组中可能没有必要，因为疤痕和复发感染的发生率很低，而且反流程度很低。最近，一种新的微创治疗反流的方法已经被开发出来，一种被称为“脱流”的材料已经被FDA批准用于这一目的。这种物质通过膀胱镜在输尿管开口周围注射。这种膨胀剂引起的孔口结构的变化可以治愈回流。由于其易用性和应用的低发病率，有人建议将其作为大多数低级别反流儿童的初始治疗。成功的脱流治疗可能会使长期监测的需要变得不必要，无论是服用还是停用抗生素。因此，对于数千名患有反流的儿童中的大多数，最佳治疗方案仍不清楚。他们仅仅需要每天使用抗生素吗？在不采取预防措施的情况下，是否可以安全地观察它们？他们需要进行非卧床膀胱镜检查吗？一项前瞻性的随机研究被提议用来回答这个问题，女孩年龄1-5岁，有II级或III级反流，在尿路感染后被诊断出来。三个主要的治疗组将是抗生素预防，观察不预防，或内窥镜治疗与去流出(ET)。检测的临床终点是反复发热性或非发热性尿路感染和肾疤痕。

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