Posterior Urethral Valves
Conditions
Keywords
Posterior urethral valves, Febrile Urinary Infection, Circumcision, Antibiotic prophylaxis
Brief summary
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)
Detailed description
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). The results from this study brought us, as well as several other teams (who either contacted us directly or as comments to our published study) to question the utility of antibiotic prophylaxis in circumcised boys with PUV (antibiotic prophylaxis has potential deleterious effects, both individually, and in terms of public health perspective). Circumcision alone could be a legitimate prophylactic strategy, in terms of balance between efficacy and risk of promoting antibiotic resistance. We therefore aim to conduct a new clinical trial in boys with PUV to assess the effects of circumcision alone (without antibiotic prophylaxis) on the risk of fUTI using an efficient randomized trial design in this pediatric rare disease setting by incorporating data from the previous CIRCUP trial. This would allow us the identify risk of presenting a febrile UTI in circumcised boys with PUV and no antibiotic prophylaxis. This would help us determine the optimal strategy for UTI prevention in this population and discuss options with the parents.
Interventions
DRUGAntibiotics strategy
daily antibiotic prophylaxis up to two years
PROCEDURECircumcision
Circumcision performed at the time of valve resection
Sponsors
University Hospital, Bordeaux
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
1 Days to 31 Days
Healthy volunteers
No
Inclusion criteria
\- 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 \-
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to first febrile urinary tract infections (fUTI) between baseline and 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median number of fUTIs | at 2 years | Median number of fUTIs at 2 years in children with at least 1 fUTI during follow-up |
| The proportion of children with worsening renal scans (defined as an increase in heterogeneity and number of cortical defects) | between baseline and 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 circumcision and antibiotic prophylaxis |
| Absolute risk difference of first fUTI with circumcision alone versus antibiotic prophylaxis alone | at 2 years | Absolute risk difference of first fUTI with circumcision alone versus antibiotic prophylaxis alone |
| Absolute risk difference of first fUTI with circumcision and antibiotic prophylaxis versus antibiotic prophylaxis alone | at 2 years | Absolute risk difference of first fUTI with circumcision and antibiotic prophylaxis versus antibiotic prophylaxis alone |
Countries
France
Contacts
CONTACTAurore Capelli, PhD
CONTACTLuke HARPER, MD
PRINCIPAL_INVESTIGATORLuke HARPER, MD
University Hospital, Bordeaux
Outcome results
None listed