Prophylactic Antimicrobials in Children with Vesicoure

水囊尿儿童的预防性抗菌药物

• 批准号: 7036313
• 负责人: ALEJANDRO HOBERMAN
• 金额: $ 33.69万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7036313
• 关键词: antiinfective agents; chemoprevention; clinical research; clinical trials; cooperative study; disease /disorder prevention /control; human subject; human therapy evaluation; infant human (0-1 year); injury; kidney disorder; patient oriented research; pediatric pharmacology; pediatrics; preschool child (1-5); relapse /recurrence; scars; urinary bladder disorder; urinary tract imaging /visualization; urinary tract infection

DESCRIPTION (provided by applicant): Urinary tract infection (UTI) affects 2.6% to 3.4% of children in the US annually, and accounts for more than 1 million office visits, 94,000 hospital outpatient visits and (40,000 admissions each year. The economic burden just for UTI hospitalizations totals $180 million. Vesicoureteral reflux (VUR) occurs in 35% of children with UTI, increasing the risk of infection and long-term sequelae. This proposal aims to evaluate the effectiveness of management strategies in improving outcomes of children with VUR. Continuous antimicrobial prophylaxis has become accepted therapy for children with VUR, although scant evidence is available to support this practice. Similarly, the role of subureteral endoscopic surgery has not been properly evaluated. Recent changes in practice underscore the importance of determining the efficacy of prophylactic antimicrobials. These include: 1) earlier diagnosis and treatment of UTIs resulting in reduced renal scarring, 2) parental awareness of increased antimicrobial resistance and willingness to follow a "watchful waiting" path; and 3) prenatal identification of functional and anatomical obstructions of the urinary tract with widespread use of ultrasound (separating these children from those diagnosed with VUR following an index UTI). This proposal consists of a multicenter, randomized, placebo-controlled, double-blind clinical trial to evaluate the efficacy of prophylactic antimicrobials in preventing renal scarring and reinfections in children aged 2-36 months old with VUR. Children with Grades l-lll VUR will be randomized to receive prophylactic antimicrobial therapy or placebo; a third arm could readily be added to evaluate the efficacy of subureteral endoscopic surgery. Children with grades IV-V VUR will receive antimicrobial prophylaxis because they have the highest risk of developing renal scarring. Children will be recruited from 1) an Acute Care Pathway and 2) a Referral Care Pathway to enhance generalizability of study findings. Children's Hospital of Pittsburgh is in a unique position to participate in this cooperative agreement as a pediatric nephrology/urology Clinical Treatment Center. Distinguishing features of our setting include 1) an interdisciplinary team of experienced clinical investigators representing the various subspecialties, which has 2) a strong record of clinical research accomplishments in pediatric UTI and VUR, and 3) extensive expertise in research methods and in recruiting and retaining a large number of children in clinical trials

描述(由申请人提供)： 尿路感染(UTI)每年影响2.6%至3.4%的美国儿童，每年有100多万人次到办公室就诊，94,000人次到医院门诊，40,000人次入院。仅UTI住院治疗的经济负担就总计1.8亿美元。膀胱输尿管反流(VUR)发生在35%的尿路感染儿童中，增加了感染和长期后遗症的风险。本提案旨在评估管理策略在改善输尿管返流儿童预后方面的有效性。持续的抗菌预防已经成为儿童输尿管返流的公认治疗方法，尽管几乎没有证据支持这一做法。同样，内窥镜手术的作用也没有得到正确的评价。最近实践中的变化强调了确定预防性抗菌剂疗效的重要性。这些措施包括：1)早期诊断和治疗尿路感染，从而减少肾疤痕形成；2)父母对抗生素耐药性增加的认识，并愿意遵循“警惕等待”的方法；3)广泛使用超声波，产前识别功能性和解剖上的尿路梗阻(根据尿路感染指数将这些儿童与被诊断为VUR的儿童区分开来)。这项建议包括一项多中心、随机、安慰剂对照、双盲临床试验，以评估预防性抗菌药在预防2-36个月大的输尿管返流儿童肾脏瘢痕和再感染方面的有效性。VUR分级为L-11VUR的儿童将随机接受预防性抗菌治疗或安慰剂治疗；可以随时增加第三只手臂，以评估输尿管下内窥镜手术的疗效。IV-V级VUR的儿童将接受抗菌预防，因为他们发展为肾脏疤痕的风险最高。将从1)急症护理途径和2)转诊护理途径招募儿童，以加强研究结果的概括性。匹兹堡儿童医院作为一家儿科肾病/泌尿外科临床治疗中心，以独特的地位参与了这项合作协议。我们环境的显著特点包括：1)由代表各个子专科的经验丰富的临床研究人员组成的跨学科团队，2)在儿科尿路感染和尿路感染方面有良好的临床研究成就，3)在研究方法和在临床试验中招募和留住大量儿童方面具有广泛的专业知识。