NCT02021006

Antibiotic Prophylaxis and Renal Damage In Congenital Abnormalities of the Kidney and Urinary Tract

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 292 (actual)
• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico · Academic / Other
• Sex: All
• Age: 1 Month – 4 Months
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. Patients enrolled will be randomized in two groups: Group A: no antibiotic prophylaxis. Group B: antibiotic prophylaxis for 24 months. The choice of which antibiotic to prescribe from the list below is left to the discretion of each investigator, on the basis of local antibiotic resistance patterns. * nitrofurantoin 1.5-2 mg/kg per day * amoxicilline/clavulanic acid 15 mg/kg per day (dose expressed in units equivalent to amoxicillin) * cefixime 2 mg/kg per day * trimethoprim/sulfamethoxazole 2.5 mg/kg per day (dose expressed in units equivalent to trimethoprim) The study is comprised of: * Phase 1: Pre-randomization - screening tests to determine eligibility for the trial. * Phase 2: Active treatment - this phase follows randomization and foresees 24 months of antibiotic prophylaxis for Group B and clinical surveillance for Group A. * Phase 3: Follow-up - a further 36 months of clinical, laboratory and instrumental evaluation of renal function and the progression of renal damage for a total follow-up period of 5 years

Conditions

• Vesicoureteral Reflux
• Renal Hypodysplasia, Nonsyndromic, 1
• Chronic Kidney Disease

Interventions

Type	Name	Description
DRUG	nitrofurantoin	antibiotic prophylaxis of urinary tract infections 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 * amoxicilline/clavulanic acid 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)
OTHER	No prophylaxis	children will be followed, but no antibiotic prophylaxis will be administered
DRUG	Amoxicillin-Potassium Clavulanate Combination	antibiotic prophylaxis of urinary tract infections 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 * amoxicilline/clavulanic acid 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)
DRUG	Trimethoprim/sulfamethoxazole	antibiotic prophylaxis of urinary tract infections 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 * amoxicilline/clavulanic acid 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)
DRUG	Cefixime	antibiotic prophylaxis of urinary tract infections 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 * amoxicilline/clavulanic acid 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)

Timeline

• Start date: 2013-12-01
• Primary completion: 2020-01-01
• Completion: 2025-01-01
• First posted: 2013-12-27
• Last updated: 2023-09-28

Locations

1 site across 1 country: Italy