Clinical trial NCT05301023: Individualized Antibiotic Therapy in Children With Acute Uncomplicated Febrile Urinary Tract Infection
Official title: Individualized Antibiotic Therapy Versus Standard Care in Children With Febrile Urinary Tract Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Febrile Urinary Tract Infection
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Hvidovre University Hospital
First posted: 2022-03-29
Enrollment: 408
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: An investigator-initiated, open-label, multi-center, randomized, non-inferiority trial of children aged 3 months to 13 years with acute uncomplicated febrile urinary tract infection. The primary objective is to determine whether individualized antibiotic therapy based on an algorithm (experimental arm) versus standard antibiotic therapy of 10 days (control arm) can reduce the number of days with antibiotic therapy within 28 days after treatment initiation without increasing the risk of recurrent urinary tract infection regardless of the pathogen or death of any cause within 28 days after end of treatment. Children will be randomized 1:1. The medical treatments received are identical in both groups.


Eligibility criteria: Inclusion Criteria:

1. Clinical suspicion of febrile (≥38 °C) urinary tract infection.
2. Positive urine culture of uropathogenic bacteria obtained by either suprapubic bladder aspiration, sterile intermittent catheterization, or midstream urine.

   1. Suprapubic bladder aspiration: any growth of bacteria.
   2. Sterile intermittent catheterization: monoculture with ≥10\^3 cfu/ml.
   3. Midstream urine x 2: Monoculture with the bacteria in both tests with ≥10\^4 cfu/ml.
   4. Midstream urine x 2: Monoculture with the bacteria in both tests with ≥10\^5 cfu/ml in one test and 10\^3 cfu/ml in another test.
   5. Midstream urine x 1 (≥10 years of age): Monoculture with ≥10\^5 cfu/ml.
3. 3 months to 13 years of age (corrected age in case of premature birth).
4. Parents fluent in Danish or English.
5. Informed consent both parents.

All children who do not receive any empirical antibiotic therapy but have a positive urine culture (approximately 48 hours after urine sample collection) can be included if fever (≥ 38.0 °C) is present and the child is initiated with relevant antibiotic therapy. ¨

Children can be included regardless of whether intravenous or oral antibiotics were given as empirical therapy.

Exclusion Criteria:

1. Non-Danish civil registration number.
2. Not resident in the Capital Region or Region Zealand in Denmark at primary visit.
3. Previous inclusion in the trial.
4. History of febrile (≥38 °C) urinary tract infection in the last 28 days before the primary visit.
5. Antibiotic treatment in the last two weeks before the primary visit.
6. Three or more episodes with febrile (≥38 °C) urinary tract infection within one year of the primary visit (including the current episode).
7. Previous complicated episode of febrile (≥38 °C) urinary tract infection (e.g., renal abscess or urosepticemia)
8. Non-compliance ≥3 doses of antibiotics during empirical therapy.
9. Elevated creatinine.
10. Prophylactic antibiotic treatment.
11. Known urogenital abnormalities (i.e., obstructing uropathies; vesicoureteral reflux; multicystic dysplasia; renal dysplasia; renal hypoplasia; renal agenesis; duplex kidney; polycystic kidney disease; neurogenic bladder dysfunction; hypospadias).
12. Septic.
13. Positive blood culture (if contamination is not suspected).
14. Immune deficiency.
15. Systemic immunosuppressive therapy.

Primary outcomes:
measure: Proportion of participants with recurrent urinary tract infection regardless of the pathogen or death of any cause
timeFrame: within 28 days after end of treatment
measure: Number of days with antibiotic therapy
timeFrame: within 28 days after treatment initiation
Secondary outcomes:
measure: Number of days with absence from school or daycare due to illness
timeFrame: within 28 days after randomization
measure: Proportion of participants with recurrent urinary tract infection regardless of the pathogen or death of any cause
timeFrame: within 100 days after end of treatment
Other outcomes:
measure: Number of hospital days related to urinary tract infection symptoms
timeFrame: within 28 days after end of treatment
measure: Number of days with a physical or virtual (phone or online) consultation
timeFrame: From date of randomization until the date of treatment stop for the baseline infection, assessed up to 14 days
measure: Proportion of participants with recurrent infection with a bacterium resistant to the antibiotic given for the primary infection
timeFrame: within 100 days after end of treatment
measure: Proportion of participants with a serious adverse event
timeFrame: within 100 days after randomization
measure: Proportion of participants with an antibiotic-related non-serious adverse event
timeFrame: within 28 days after randomization
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital Rigshospitalet
city: Herlev
country: Denmark
facility: Copenhagen University Hospital Herlev
city: Hillerød
country: Denmark
facility: Copenhagen University Hospital Hillerød
city: Holbæk
country: Denmark
facility: Copenhagen University Hospital Holbæk
city: Hvidovre
country: Denmark
facility: Copenhagen University Hospital Hvidovre
city: Nykøbing Falster
country: Denmark
facility: Copenhagen University Hospital Nykøbing Falster
city: Roskilde
country: Denmark
facility: Copenhagen University Hospital Roskilde
city: Slagelse
country: Denmark
facility: Copenhagen University Hospital Slagelse
Study officials:
affiliation: Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark
name: Naqash Sethi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark
name: Ulrikka Nygaard, Ass. prof, Ph.D.
role: STUDY_CHAIR
References: