Individualized Antibiotic Therapy in Children With Acute Uncomplicated Febrile Urinary Tract Infection

NCT05301023 | Completed Phase 4 DMC

• 1 other identifier: H-21057310 (UVI RCT)
• Study Type: interventional
• Target: 408
• Locations: 1 country
• Sites: 8

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.

Conditions

Febrile Urinary Tract Infection

Outcome Measures

Primary Outcomes (2)

• Proportion of participants with recurrent urinary tract infection regardless of the pathogen or death of any cause

  within 28 days after end of treatment

• Number of days with antibiotic therapy

  within 28 days after treatment initiation

Secondary Outcomes (2)

• Number of days with absence from school or daycare due to illness

  within 28 days after randomization

• Proportion of participants with recurrent urinary tract infection regardless of the pathogen or death of any cause

  within 100 days after end of treatment

Other Outcomes (5)

• Number of hospital days related to urinary tract infection symptoms

  within 28 days after end of treatment

• Number of days with a physical or virtual (phone or online) consultation

  From date of randomization until the date of treatment stop for the baseline infection, assessed up to 14 days

• Proportion of participants with recurrent infection with a bacterium resistant to the antibiotic given for the primary infection

  within 100 days after end of treatment

Study Arms (2)

Individual group

EXPERIMENTAL

In the individual group, the participants receive individualized antibiotic therapy.

Other: Individualized antibiotic therapy

Standard group

ACTIVE COMPARATOR

In the standard group, the participants receive standard antibiotic therapy as defined by the national guideline.

Other: Standard antibiotic therapy

Interventions

Individualized antibiotic therapy OTHER

Individualized antibiotic therapy is based on the duration of illness after treatment initiation, as the antibiotic therapy can be stopped three days after the participant has become healthy. The participant is classified as healthy if he/she is afebrile (\<38.0 °C), has experienced significant clinical improvement, and have no flank pains or dysuria.

Individual group

Standard antibiotic therapy OTHER

Standard antibiotic therapy is 10 days of antibiotic therapy regardless of the duration of illness after treatment initiation.

Standard group

Eligibility Criteria

• Age: 3 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Clinical suspicion of febrile (≥38 °C) urinary tract infection.
• Positive urine culture of uropathogenic bacteria obtained by either suprapubic bladder aspiration, sterile intermittent catheterization, or midstream urine.
• Suprapubic bladder aspiration: any growth of bacteria.
• Sterile intermittent catheterization: monoculture with ≥10\^3 cfu/ml.
• Midstream urine x 2: Monoculture with the bacteria in both tests with ≥10\^4 cfu/ml.
• 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.
• Midstream urine x 1 (≥10 years of age): Monoculture with ≥10\^5 cfu/ml.
• months to 13 years of age (corrected age in case of premature birth).
• Parents fluent in Danish or English.
• 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.

You may not qualify if:

• Non-Danish civil registration number.
• Not resident in the Capital Region or Region Zealand in Denmark at primary visit.
• History of febrile (≥38 °C) urinary tract infection in the last 28 days before the primary visit.
• Antibiotic treatment in the last two weeks before the primary visit.
• Three or more episodes with febrile (≥38 °C) urinary tract infection within one year of the primary visit (including the current episode).
• Previous complicated episode of febrile (≥38 °C) urinary tract infection (e.g., renal abscess or urosepticemia)
• Non-compliance ≥3 doses of antibiotics during empirical therapy.
• Elevated creatinine.
• Prophylactic antibiotic treatment.
• 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).
• Septic.
• Positive blood culture (if contamination is not suspected).
• Immune deficiency.
• Systemic immunosuppressive therapy.

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Hvidovre University Hospital: collaborator

Study Sites (8)

Copenhagen University Hospital Rigshospitalet

Copenhagen, 2100, Denmark

Location

Copenhagen University Hospital Herlev

Herlev, 2730, Denmark

Location

Copenhagen University Hospital Hillerød

Hillerød, 3400, Denmark

Location

Copenhagen University Hospital Holbæk

Holbæk, 4300, Denmark

Location

Copenhagen University Hospital Hvidovre

Hvidovre, 2650, Denmark

Location

Copenhagen University Hospital Nykøbing Falster

Nykøbing Falster, 4800, Denmark

Location

Copenhagen University Hospital Roskilde

Roskilde, 4000, Denmark

Location

Copenhagen University Hospital Slagelse

Slagelse, 4200, Denmark

Location

Related Publications (2)

• Sethi NJ, Carlsen ELM, Tabassum A, Cortes D, Mark Ow S, Schmidt IM, Christensen MM, Kirkedal AK, Kai CM, Bjerre CK, Jensen LH, Antonova M, Sonderkaer S, Rytter MJH, Tordrup G, Zaharov T, Sehested LT, Nygaard U. Efficacy and safety of individualised versus standard 10-day antibiotic treatment in children with febrile urinary tract infection (INDI-UTI): a pragmatic, open-label, multicentre, randomised, controlled, non-inferiority trial in Denmark. Lancet Infect Dis. 2025 Aug;25(8):925-935. doi: 10.1016/S1473-3099(25)00075-1. Epub 2025 Apr 2.

  PMID: 40187361 DERIVED

• Sethi N, Carlsen ELM, Schmidt IM, Cortes D, Nygaard U, Sehested LT. Individualised versus standard duration of antibiotic therapy in children with acute uncomplicated febrile urinary tract infection: a study protocol and statistical analysis plan for a multicentre randomised clinical trial. BMJ Open. 2023 Jun 9;13(6):e070888. doi: 10.1136/bmjopen-2022-070888.

  PMID: 37295836 DERIVED

Study Officials

• Naqash Sethi, MD

  Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark

  PRINCIPAL INVESTIGATOR

• Ulrikka Nygaard, Ass. prof, Ph.D.

  Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: March 29, 2022
• Study Start: April 1, 2022
• Primary Completion: February 29, 2024
• Study Completion: June 8, 2024
• Last Updated: July 8, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Primarily for the conduction of individual participant data meta-analysis.

Locations

DK (8)