A Multicenter Randomized Controlled Trial Comparing Short-Course Amoxicillin/Clavulanic Acid After Fever Resolution to Standard 10-Day Regimen for Febrile Urinary Tract Infections in Children

The primary objective is to assess whether antibiotic therapy using amoxicillin and clavulanic acid, administered for 24 hours following fever resolution, is non-inferior to a standard 10-day regimen regarding the rate of urinary tract infection recurrence within 30 days post-treatment. The secondary objectives include:

• Evaluation of short-term clinical efficacy, defined as the complete resolution of infection symptoms without requiring alternative antibiotic therapy.
• Assessment of antibiotic-resistant or opportunistic strains in cases of relapse.

The sponsor did not provide information regarding the total number of participants. The study population consists of pediatric patients, including both males and females, within the age range of 3 months to 3 years. Participants are selected based on a clinical diagnosis of febrile urinary tract infection, characterized by a temperature of ≥38°C and positive results for nitrite or leukocyte esterase during urinalysis. A diagnosis is confirmed via a positive urine culture demonstrating bacterial growth exceeding 10^5 CFU/ml, or 10^4 CFU/ml in samples obtained through bladder catheterization. Inclusion requires written informed consent from parents or legal guardians.

This multicenter, randomized controlled trial evaluates the efficacy of a personalized antibiotic treatment for pediatric urinary tract infections. The study compares a regimen of amoxicillin and clavulanic acid, administered for 24 hours following the resolution of fever, against a standard 10-day regimen. The primary objective is to assess the non-inferiority of the abbreviated treatment regarding the rate of infection recurrence, which is defined as the reappearance of clinical signs and symptoms within 30 days following the completion of antibiotic therapy. Participants must be between 3 months and 3 years of age and meet specific clinical criteria, including fever $\geq$38°C and positive urinalysis confirmed by a positive urine culture. Secondary endpoints include the evaluation of short-term clinical efficacy and the rate of emergence of antibiotic resistance or opportunistic strains in cases of suspected relapse. The study protocol involves a screening period to confirm the diagnosis, followed by the treatment phase and subsequent follow-up visits to monitor for recurrence. The total duration of participant involvement is determined by the 30-day post-treatment observation period.

The experimental treatment consists of amoxicillin and clavulanic acid administered as an oral suspension (Augmentin Fruit, 400 mg/57 mg/5 ml). The total dosage is 3 g administered via the oral route. This regimen is continued for a period of 24 hours following the resolution of fever.

The comparator treatment is a standard-of-care antibiotic regimen consisting of a 10-day course of therapy. The study aims to evaluate the non-inferiority of the abbreviated regimen regarding the rate of urinary tract infection recurrence, defined as the reappearance of clinical signs and symptoms within 30 days after the completion of antibiotic therapy.

The primary efficacy endpoint is the rate of infection recurrence, which is defined as the reappearance of clinical signs and symptoms of febrile urinary tract infection accompanied by a positive urine culture within 30 days following the completion of antibiotic therapy. Efficacy will be assessed by comparing a 24-hour treatment period after fever resolution to a standard 10-day regimen to determine non-inferiority.

Secondary efficacy assessments include:

• Short-term clinical efficacy, evaluated through clinical assessment and urinalysis during the follow-up period.
• The rate of emergence of antibiotic resistance or opportunistic strains in cases of suspected relapse. This is defined by a positive urinalysis and a positive urine culture for a single bacterial type resistant to amoxicillin and clavulanic acid. Bacterial growth is considered significant if concentrations exceed 10⁵ CFU/ml, or 10⁴ CFU/ml for samples obtained via bladder catheterization.