Antibiotic Prophylaxis and Renal Damage In Congenital Abnormalities of the Kidney and Urinary Tract
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 292
- 试验地点
- 1
- 主要终点
- urinary tract infections rate
研究概览
简要总结
The exact role of urinary tract infection in the appearance of chronic kidney disease is unclear. Children with congenital malformations of kidney and urinary tract have the higher risk of impairment of renal function. To understand if the use of antibiotic prophylaxis can reduce the risk of urinary tract infection in children with these malformations, this study will randomize children in two groups. Group A will not take antibiotic prophylaxis, Group B will take antibiotic prophylaxis for 2 years. This study will assess if antibiotic prophylaxis reduce the risk of urinary tract infections in these children and if urinary tract infections influence the appearance of renal damage.
Our hypothesis is that prophylaxis reduce the risk of infection in severe vesicoureteral reflux and that urinary tract infections, in morphologically normal kidneys, will not result in chronic renal failure.
详细描述
Bacterial urinary tract infections (UTI) are common in young children. The presence of fever is considered to be a marker of renal parenchymal involvement. Renal damage during the acute phase of infection may lead to scarring, yet the role that scarring plays in the appearance of chronic kidney failure is unknown. It is also unclear what influence scars have on the natural course of kidney function, especially in children with renal hypodysplasia, with or without vesicoureteral reflux (VUR). Renal hypodysplasia is the most common cause for dialysis and transplantation in the pediatric population.
Patients suffering from recurrent UTIs and VUR have often undergone corrective surgery. For many years, it was also thought necessary to prescribe long-term antibiotic prophylaxis to all children with VUR. These treatment strategies were based on the ideas and opinions of the experts, rather than on hard scientific evidence. As regards the prevention of recurrent UTIs and the subsequent development of renal scarring, a long-term international study on Reflux was not able to demonstrate that surgical correction is more effective than antibiotic prophylaxis. Very little data is available regarding the use of long-term antibiotic prophylaxis in children with high grade reflux with or without renal hypodysplasia.
The use of antibiotics during the first few months of life has been associated with a significant increase in body mass index (BMI). Even though this effect is probably limited, it could have a significant impact on public health given the widespread use of antibiotics and due to the considerable increase in cases of pediatric and adult obesity seen over the last few years.
In spite of the lack of evidence, the use of prophylaxis is largely routine practice in most centres. Therefore, a randomized study is necessary in order to evaluate whether prophylaxis reduces the risk of symptomatic infections and subsequent renal damage.
To assess the role of prophylaxis in patient with high grade vesicoureteral reflux we will perform a multicentre, prospective, randomized, controlled, open-label, study.
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
- 1 Month 至 4 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 1 and 4 months (> 4 weeks and <20 weeks of post-natal age)
- •Gestational age > 35 weeks
- •Glomerular filtration rate (calculated according to Schwartz) > 15 ml/min/1.73 m2
- •No previous symptomatic UTI
- •Imaging Diagnostic work-up completed and presence of grade III to V vesicoureteral reflux
- •Informed consent of parents
排除标准
- •Age <1 and >4 months
- •Gestational age < 35 weeks
- •Glomerular filtration rate (calculated according to Schwartz) < 15 ml/min/1.73 m2 at three months of age
- •Patients with neurogenic bladder, myelomeningocele, ureteropelvic junction and/or ureterovesical junction obstruction, or other malformations leading to potential voiding disturbances.
- •Presence of urethral valves
- •Patients with no or low grade reflux (grade I and II).
- •Hypersensitivity to the all the utilized antimicrobial agent
- •Children with serious clinical conditions which, according to the investigator, prevent them from being included in the study cohort.
- •Use of experimental drugs in the month previous to the beginning of the study
- •Children unable to follow the established protocol procedures or whose parents are unable to sign the informed consent.
研究组 & 干预措施
ANTIBIOTIC PROPHYLAXIS
Children in this arm will take antibiotic prophylaxis for 2 years. Patients in this arm will do clinical/instrumental follow-up for 5 years.
The antibiotic for prophylaxis will be chosen by Physicians according to the local resistance spectrum of bacteria responsible of UTIs
Physicians can chose one the following schedules:
- nitrofurantoin 1.5-2 mg/kg per day
- Amoxicillin-Potassium Clavulanate Combination 15 mg/kg per day (dose expressed in units equivalent to amoxicilline)
- cefixime 2 mg/kg per day
- trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim)
干预措施: nitrofurantoin (Drug)
ANTIBIOTIC PROPHYLAXIS
Children in this arm will take antibiotic prophylaxis for 2 years. Patients in this arm will do clinical/instrumental follow-up for 5 years.
The antibiotic for prophylaxis will be chosen by Physicians according to the local resistance spectrum of bacteria responsible of UTIs
Physicians can chose one the following schedules:
- nitrofurantoin 1.5-2 mg/kg per day
- Amoxicillin-Potassium Clavulanate Combination 15 mg/kg per day (dose expressed in units equivalent to amoxicilline)
- cefixime 2 mg/kg per day
- trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim)
干预措施: Amoxicillin-Potassium Clavulanate Combination (Drug)
ANTIBIOTIC PROPHYLAXIS
Children in this arm will take antibiotic prophylaxis for 2 years. Patients in this arm will do clinical/instrumental follow-up for 5 years.
The antibiotic for prophylaxis will be chosen by Physicians according to the local resistance spectrum of bacteria responsible of UTIs
Physicians can chose one the following schedules:
- nitrofurantoin 1.5-2 mg/kg per day
- Amoxicillin-Potassium Clavulanate Combination 15 mg/kg per day (dose expressed in units equivalent to amoxicilline)
- cefixime 2 mg/kg per day
- trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim)
干预措施: Trimethoprim/sulfamethoxazole (Drug)
ANTIBIOTIC PROPHYLAXIS
Children in this arm will take antibiotic prophylaxis for 2 years. Patients in this arm will do clinical/instrumental follow-up for 5 years.
The antibiotic for prophylaxis will be chosen by Physicians according to the local resistance spectrum of bacteria responsible of UTIs
Physicians can chose one the following schedules:
- nitrofurantoin 1.5-2 mg/kg per day
- Amoxicillin-Potassium Clavulanate Combination 15 mg/kg per day (dose expressed in units equivalent to amoxicilline)
- cefixime 2 mg/kg per day
- trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim)
干预措施: Cefixime (Drug)
NO PROPHYLAXIS
Children in this arm will not take antibiotic prophylaxis. Patients in this arm will do clinical/instrumental follow-up for 5 years
干预措施: No prophylaxis (Other)
结局指标
主要结局
urinary tract infections rate
时间窗: during the first 24 months from enrolment
Urinary tract infections will be strictly monitored in all enrolled patients (both group A and group B). The rate of urinary tract infections in the first 24 months from the enrolment will be compared between 2 groups
次要结局
- renal scars(at 2 years and 5 years from enrolment)
- serum creatinine (renal function)(at the enrolment,1 year, 2 years, 3 years, 4 years, 5 years)
- hypertension(at 4, 8, 12, 18, 24, 36, 48, 60 months from enrolment)
- proteinuria(at 4, 8, 12, 18, 24, 36, 48, 60 months from enrolment)
- body mass index(at 2 and 5 years from enrolment)
- febrile urinary tract infections(during the first 24 months from enrolment)
- serum cystatin C (renal function)(at the enrolment,1 year, 2 years, 3 years, 4 years, 5 years)
- modification in gut microbiota induced by continuous antibiotic exposure during the first months of life(at the enrollment, 4 months, 8 months, 12 months, 2 years, 3 years, 4 years, 5 years)
研究者
Giovanni Montini
Prof.
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico