Evaluation of the Effectiveness of Antibiotic Prophylaxis in Children With a History of Upper Urinary Tract Infections:a Multicentre Randomised Study
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 660
- 试验地点
- 18
- 主要终点
- The primary end-point is UTI Recurrence Rate during the 12-month observation period and the Development of renal damage (parenchymal scar) after 12 months.
研究概览
简要总结
Our hypothesis is that long-term antimicrobial prophylaxis does not reduce the recurrence of infection and the risk of appearance of kidney scars in children with a documented previous upper UTI.
详细描述
Background
Upper urinary tract infections (UTI) are common in children, especially when functional and anatomical abnormalities of the urinary tract co-exist, such as vesico-ureteral reflux (VUR), urinary tract obstruction uropathy and bladder dysfunction. They are associated with the risk of long-term complications, including permanent renal damage (renal scarring), which occurs in 15% of cases. The objective of the diagnosis and medical treatment of UTI in children is the prevention of such complications. Medical treatment includes long-term antimicrobial prophylaxis to be continued for periods ranging from 6 months to 2 years. Recent studies have revealed the emergence of therapy-induced resistance. A review of the literature has highlighted the lack of properly designed, large clinical trials, demonstrating the efficacy of long-term low-dose antimicrobial prophylaxis in terms of reduction in UTI recurrence.
Methods and design
The study is a controlled, randomised, open-label, 3-armed, parallel-group clinical trial comparing no prophylaxis (group 1) with prophylaxis with co-trimoxazole 15 mg/kg daily (group 2) and with amoxicillin + clavulanic acid 15 mg/kg daily (group 3) for 12 months.
Assuming that the incidence of recurrences is 20%, defining efficacy as an incidence of 10% per group and setting error = 0.05 and power = 90%, 220 patients per group (i.e. a total of 660 patients) are required The study population will consist of children aged between 2 months and 6 years, with normal renal function (creatinine clearance 70 ml/min/1.73m2) and a first episode of documented UTI, who presents at least one of the following: an acute pyelonephritic lesion at the DMSA scan and/or a VUR at the baseline micturating cystography.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 2 Months 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 2 months and 6 years
- •Creatinine clearance (calculated according to Schwartz) 70 ml/min/1.73 m2 (for children in their first year of life, serum creatinine levels within normal range for age and sex)
- •First documented upper UTI (diagnostic criteria in Table 1)
- •Imaging Diagnostic work-up completed (Table 2) with at least the presence of an acute lesion at the DMSA scan and or a primary non severe reflux ( 1st or 3rd degree)
- •Informed consent of parents
排除标准
- •Patients with chronic renal insufficiency or 30% relative function of one kidney at DMSA scan
- •Patients with urinary tract disorders, such as vesico-ureteral reflux due to complex malformations of the urinary tract, obstruction of the posterior urethra, ureterocele or single kidney, neurogenic bladder
- •Patients with reflux 4th degree
- •Patients with pyelonephritis that developed during prophylaxis instituted because of prenatal diagnosis of urinary tract dilatation Hypersensitivity to one of the two selected antimicrobial agents
结局指标
主要结局
The primary end-point is UTI Recurrence Rate during the 12-month observation period and the Development of renal damage (parenchymal scar) after 12 months.
次要结局
- The secondary objectives are the comparison, in terms of efficacy and effectiveness, between two antimicrobial agents that are currently approved for prophylactic use: co-trimoxazole 15 mg/kg daily versus amoxicillin + clavulanic acid 15 mg/kg daily.