Clinical Trial of Prophylactic Antibiotics for Children with Vesicoureteral Reflu

描述（由申请人提供）： 项目摘要：尿路感染（UTI）是儿童时期最常见的严重细菌感染，约占6岁儿童的3%。目前对患有UTI的幼儿的护理标准是进行排尿性膀胱尿道造影（VCUG），以评估膀胱输尿管反流（VUR）的存在，这种情况存在于约30-40%的UTI儿童中，并被认为会增加肾瘢痕形成的风险。传统上，VCUG上确定的VUR儿童每天接受预防性抗生素治疗，直到VUR消退或手术矫正VUR。最近，VUR在促成肾瘢痕形成中的作用以及VCUG、预防性抗生素和VUR手术的效用受到质疑。人们还对VCUG和日常预防性抗生素的成本和潜在危害表示担忧。在本U 01申请中，我们提出了一项多中心、中心随机、双盲、安慰剂对照、等效性试验，以确定在及时识别UTI症状和早期治疗确诊UTI的情况下，预防性抗生素在减少肾瘢痕形成方面是否优于安慰剂;以及在UTI出现时，DMSA肾瘢痕形成或肾盂肾炎证据是否改变了预防性抗生素的效果。我们还将确定抗生素预防是否增加抗生素抗性大肠杆菌和克雷伯氏菌属的胃肠道（GI）定殖率。和Gl定殖与假单胞菌属（Pseudomonaspp.）认识到本U 01选择的临床试验中心（CTC）实施的方案将通过共识[sic]制定，本申请还描述了费城儿童医院（CHOP）作为NIDDK膀胱输尿管反流临床研究中潜在CTC的优势。这些包括（1）在大型临床研究中招募和留住患者的内容领域专业知识和经验，（2）从其中招募患者的初级保健和泌尿科实践的庞大儿科医疗保健网络，（3）适用于识别潜在参与者的全网络最先进的可搜索电子病历和计费系统，及（4）为进行最高质素的临床研究而设立的机构承诺及基础设施。 相关性：这项试验有可能对美国每年成千上万的UTI儿童的诊断和管理产生重大影响

DESCRIPTION (provided by applicant): Project Summary: Urinary tract infection (UTI) is the most common serious bacterial infection in childhood, affecting approximately 3% of all children by six years of age. The current standard of care for young children who present with UTI is to perform a voiding cystourethrogram (VCUG) to evaluate for the presence of vesicoureteral reflux (VUR), a condition that is present in approximately 30-40% of children with UTI and is thought to increase the risk of renal scarring. Traditionally, children with VUR identified on VCUG are treated with daily prophylactic antibiotics until the VUR resolves, or have surgical correction of the VUR. Recently the role of VUR in contributing to renal scarring and the utility of VCUG, prophylactic antibiotics and VUR surgery have been questioned. Concerns have also been raised about the cost and potential harms of VCUGs and daily prophylactic antibiotics. In this U01 application we propose a multi-center, centrally randomized, double-blind, placebo-controlled, equivalence trial to determine whether, in the setting of prompt recognition of UTI symptoms and early treatment of confirmed UTI, prophylactic antibiotics are better than placebo in reducing renal scarring; and whether DMSA evidence of renal scarring or pyelonephritis at presentation of UTI modifies the effect of prophylactic antibiotics. We will also determine whether antibiotic prophylaxis increases the rate of gastrointestinal (Gl) colonization with antibiotic resistant E.coli and Klebsiella spp. and Gl colonization with Pseudomonas spp. Recognizing that the protocols implemented by the Clinical Trial Centers (CTCs) selected for this U01 will be developed by concensus [sic], this application also describes the strengths that the Children's Hospital of Philadelphia (CHOP) brings as a potential CTC in the NIDDK's Clinical Study of Vesicoureteral Reflux. These include (1) content area expertise and experience recruiting and retaining patients in large clinical studies, (2) a vast pediatric healthcare network of primary care and urology practices from which to recruit patients, (3) a network-wide state-of-the-art searchable electronic medical record and billing system suitable for identifying potential participants, and (4) an institutional commitment to and infrastructure for conducting the highest quality clinical research. Relevance: The trial has the potential to substantially impact the diagnostic work-up and management for the tens of thousands of children in the US who develop UTIs each year