Efficacy and Safety of Circumcision Alone on Risk of Febrile Urinary Tract Infections in Boys With Posterior Urethral Valves: a Prospective Randomized Open-label Multicentric Trial Enriched With Historic Controls.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 72
- 试验地点
- 13
- 主要终点
- Time to first febrile urinary tract infections (fUTI) between baseline and 2 years
研究概览
简要总结
Boys with posterior urethral valves (PUV) are at increased risk of developing febrile urinary tract infections (fUTIs). As shown in the CIRCUP trial, circumcision plus antibiotic prophylaxis reduces the risk of FUTIs compared with antibiotic prophylaxis alone. This multicenter randomised controlled trial prospectively compares circumcision alone with circumcision plus antibiotic prophylaxis for the prevention of fUTIs in boys with PUV, enriched with external historical data from the CIRCUP trial)
详细描述
Posterior urethral valves (PUV) are the most common cause of Lower Urinary Tract Obstruction (LUTO) in boys. They affect around 1:5000 births, causing increased intravesical pressure during fetal kidney development. They are associated with congenital renal dysplasia, abnormal bladder function and represent the most common obstructive cause of End-Stage Renal Failure in childhood. Postnatal primary valve ablation is the treatment of choice.
Despite optimal postnatal management, these patients present an increased risk of febrile urinary tract infection (fUTI). Febrile urinary tract infections in infants cause morbidity, require intravenous treatment and if they recur, can contribute to renal damage. Long-term prophylactic antibiotic treatment was therefore, until recently, the standard of care.
At the same time, circumcision was also supposed to decrease the rate of fUTI. This is why we conducted, between 2012 and 2017, the CIRCUP randomized controlled trial (PHRC-I) to determine whether circumcision in addition to antibiotic prophylaxis further decreased the risk of fUTI in boys with PUV, within the first two years of life.
We chose boys with PUV as they were undergoing surgery for their valve resection in any case, and the circumcision did not require an additional anaesthesia.
The results of the CIRCUP study were clear. The risk of fUTI was 3% in the Circumcision and antibiotic prophylaxis group vs 20% in the antibiotic prophylaxis alone group (RR: 10.3 (95% CI: 1.3 - 82.5)) (Circumcision and risk of febrile urinary tract infection in boys with posterior urethral valves. Harper L et al. 2022. Eur Urol (5), Annex 1).
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 Day 至 31 Days（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •- Inclusion Criteria:
- •For prospective groups:
- •Male child aged 1 to 31 days Posterior urethral valves diagnosed by cystography within the first 28 days of life Valve resection and circumcision performed before 1 month of life. Adult guardians (>18 years) Parental guardians affiliated with a social security system Parental guardians who have signed an informed consent allowing their child to participate in the study Parental guardians giving consent must be able to understand the trial in its entirety
- •For retrospective groups from CIRCUP : Parental guardians who are not opposed to their child's participation in the trial
排除标准
- •Mental state rendering the person giving consent incapable of understanding the trial Parents being a relative of the investigator or a relative of someone from the team directly involved in the trial, including assistant doctors, pharmacists, nurses, and trial coordinators Known contra-indication to all antibiotics used in the study (alfatil, Bactrim, augmentin) Long-term antibiotics use indicated for other reasons than PUV
研究组 & 干预措施
Research strategy
Prospective strategy administered to participants of CIRCUP 2: Antibiotics-sparing strategy: Circumcision alone, performed at the time of valve resection
干预措施: Circumcision (Procedure)
Reference strategy 1
Circumcision, performed at the time of valve resection, plus daily antibiotic prophylaxis up to two years Prospective strategy administered to participants of CIRCUP 2 + Use of data from historical controls from CIRCUP
干预措施: Antibiotics strategy (Drug)
Reference strategy 1
Circumcision, performed at the time of valve resection, plus daily antibiotic prophylaxis up to two years Prospective strategy administered to participants of CIRCUP 2 + Use of data from historical controls from CIRCUP
干预措施: Circumcision (Procedure)
Reference strategy 2
Daily antibiotic prophylaxis up to two years Use of data from historical controls from CIRCUP
干预措施: Antibiotics strategy (Drug)
结局指标
主要结局
Time to first febrile urinary tract infections (fUTI) between baseline and 2 years
时间窗: between baseline and 2 years
The diagnosis of fUTI is defined as fever (\>38.5° Celsius) with evidence of pyuria and culture-proven infection on urinalysis, obtained by urethral catheterization or suprapubic aspiration, as well as biological signs of inflammation.
次要结局
- Median number of fUTIs(at 2 years)
- The proportion of children with worsening renal scans (defined as an increase in heterogeneity and number of cortical defects)(between baseline and 2-years)
- Absolute risk difference of first fUTI with circumcision alone versus circumcision and antibiotic prophylaxis(at 2 years)
- Absolute risk difference of first fUTI with circumcision alone versus antibiotic prophylaxis alone(at 2 years)
- Absolute risk difference of first fUTI with circumcision and antibiotic prophylaxis versus antibiotic prophylaxis alone(at 2 years)