Fosfomycin for treating antibiotic-resistant urinary tract infections in children

Fosfomycin Versus Standard of Care in Children With Antibiotic-resistant Urinary Tract Infections: A Non-inferiority, Pragmatic, Multi-centre Adaptive Trial to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of Oral Fosfomycin in Children With Antibiotic-resistant Urinary Tract Infections.

This study is testing if fosfomycin can help children with antibiotic-resistant urinary tract infections feel better compared to standard treatments.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 6 Months to 17 Years
• Sex: All
• Sponsor: University of Sydney (Academic / other)
• Locations: 5 sites (Sydney, New South Wales and 4 other locations)
• Trial ID: NCT05709028 on ClinicalTrials.gov

What this trial studies

This Phase 3 clinical trial aims to evaluate the effectiveness of fosfomycin compared to standard care in children aged 6 months to 18 years with antibiotic-resistant urinary tract infections (UTIs). Participants will be randomly assigned to receive either oral fosfomycin or standard antibiotics based on physician preference. The study will assess the treatment outcomes for both complicated and uncomplicated UTIs, with a focus on reducing hospital admissions and improving patient management. The trial will involve multiple centers and aims to recruit up to 300 participants.

Who should consider this trial

Good fit: Ideal candidates include children aged 6 months to 18 years with microbiologically confirmed antibiotic-resistant urinary tract infections.

Not a fit: Patients with UTIs caused by organisms not susceptible to fosfomycin or those who have received more than 48 hours of effective antibiotics prior to enrollment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a safer and more effective oral treatment option for children with antibiotic-resistant UTIs, potentially reducing hospital stays.

How similar studies have performed: While fosfomycin has shown efficacy in adults, its use in children is limited, making this approach relatively novel.

Eligibility criteria

Inclusion Criteria:

Children aged ≥6 months to \<18 years with:

1. Symptoms consistent with a clinical diagnosis of a UTI (as per the treating clinician); AND
2. Microbiological confirmation: Defined as a urine culture revealing a predominant growth of a bacterial uropathogen \[≥10\^6 CFU/L, or ≥10\^3 CFU/mL\] together with ≥10x10\^6 white blood cells on microscopy; AND
3. The bacterial uropathogen is a non-pseudomonal gram-negative organism likely to cause urinary tract infections in children; being one of either: Escherichia coli, Proteus spp., Klebsiella spp., Enterobacter spp., Serratia spp., or Citrobacter spp., AND
4. The uropathogen has in vitro evidence of resistance to all oral penicillins and oral first- and second- generation cephalosporins (or is presumed to be resistant based on the pattern of phenotypic testing); AND
5. The patient has not yet received \>48 hours of antibiotics with in vitro activity against the urinary pathogen prior to enrolment.

   Exclusion Criteria:
6. Evidence of bacteraemia due to the same uropathogen within the same clinical illness; OR
7. Evidence of infection at a secondary site (such as meningitis or endocarditis); OR
8. Children with features suggestive of sepsis (defined as requiring inotropic support, or \>20ml/kg fluid bolus); OR
9. Children who are unable to tolerate or absorb oral antibiotics; OR
10. Children with severe renal unsifficiency (creatinine clearance \<10ml/minute/1.73m\^2); OR
11. Known allergy to fosfomycin; OR
12. A decision by the primary treating physician that enrolment in the trial is not in the child's best interest.

Where this trial is running

Sydney, New South Wales and 4 other locations

• Sydney Childrens Hospital — Sydney, New South Wales, Australia (Recruiting)
• The Children's Hospital at Westmead — Sydney, New South Wales, Australia (Not_yet_recruiting)
• Queensland Children's Hospital — Brisbane, Queensland, Australia (Recruiting)
• Royal Childrens Hospital — Melbourne, Victoria, Australia (Recruiting)
• Perth Children's Hospital — Perth, Western Australia, Australia (Recruiting)

Study contacts

• Principal investigator: Phoebe Williams — University of Sydney
• Study coordinator: Michelle L Harrison

Conditions Urinary Tract Infections