RIVUR Study

原发性膀胱输尿管反流(VUR)是儿童最常见的泌尿系统异常，发病率约为1%，在发热尿路感染(UTI)后确诊时增加到30%-40%。输尿管返流易发生尿路感染，并与肾脏瘢痕形成有关，可导致高血压、蛋白尿和进行性肾损害。目前对VUR的治疗是在选定的病例中通过手术干预进行长期的抗菌预防。然而，目前还没有设计良好的前瞻性研究来证实这种治疗方法对患者是有益的。2005年12月，美国国立卫生研究院/美国国立卫生研究院发起了针对膀胱输尿管返流儿童的随机干预研究，该研究是一项多中心、随机、双盲、安慰剂对照试验，旨在确定在预防L-IV级膀胱输尿管反流患儿的尿路感染复发和肾脏瘢痕形成方面，每日使用抗菌药物是否优于安慰剂。研究对象还被评估细菌耐药性、便秘、排尿功能障碍、肾功能变化、生活质量、用药依从性和卫生资源的利用。血液和尿液储存库样本被收集用于遗传学和其他辅助研究。为了验证研究假设，总共600名儿童将被随机分配到每日抗菌预防(甲氧苄啶-磺胺甲恶唑)或安慰剂(每组300人)，并跟踪观察2年。这项研究的招募始于2007年5月，截至2009年11月6日，373名患者(62%)已被随机分配，其中包括从底特律核心临床站点招募的120名患者中的68名(57%)。根据目前的征聘预测，到2010年12月，第600名参与者将被随机分配，这将需要跟踪到2012年12月。然而，RIVUR研究目前的资金将于2010年5月到期。这项申请的主要目的是获得资金，以确保成功完成这项非常重要且设计独特的研究的持续的患者登记、评估、随访和数据收集，该研究已经随机收集了有史以来为VUR双盲、安慰剂对照研究收集的最大数量的最佳定义幼儿队列。

Primary vesicoureteric reflux (VUR) is the most common urological abnormality in children, with a prevalence of about one percent, which increases to 30%- 40% when diagnosed after febrile urinary tract infection (UTI). VUR predisposes to UTI and is associated with renal scarring, which may cause hypertension, proteinuria, and progressive renal damage. The current treatment of VUR is long-term antimicrobial prophylaxis with surgical intervention in selected cases. However, there has been no well-designed prospective study to validate that this management is beneficial to the patient. In December 2005, NIH/NIDDK initiated the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) study, which is a multicenter, randomized, double-blind, placebo-controlled trial designed to determine whether daily antimicrobial prophylaxis is superior to placebo in preventing recurrent UTI and renal scarring in children with grade l-IV VUR. The study subjects are also evaluated for bacterial resistance, constipation, voiding dysfunction, changes in renal function, quality of life, medication compliance, and the utilization of health resources. Blood and urine repository samples are collected for genetic and other ancillary studies. To test the study hypotheses, a total of 600 children will be randomly assigned to daily antimicrobial prophylaxis (trimethoprim-sulfamethoxazole) or placebo (300 in each group) and followed for a 2-year period. The recruitment for the study started in May 2007 and as of November 6, 2009, 373 (62%) patients have been randomized, which includes 68 (57%) of the 120 patients to be recruited from Detroit Core Clinical Site. Based on the current recruitment projections, the 600th participant will be randomized by December 2010, who will need to be followed until December 2012. However, the current funding for the RIVUR study expires in May 2010. The main objective of this application is to obtain funding to ensure continued patient enrollment, evaluation, follow-up, and data collection for a successful completion of this very important and uniquely designed study, which has already randomized the largest number of best defined cohort of young children ever collected for a double-blind, placebo controlled, study on VUR.