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.

FosUTI

Urinary tract infections (UTIs) are among the most common bacterial infections in children. Up to 50% of UTI's are caused by multi-drug resistant ESBL-producing gram negative bacteria that do not respond to treatment with oral penicillin's or cephalosporins. Instead, children often require hospital admission to receive broad-spectrum intravenous antibiotics when they may otherwise be safely managed at home; resulting in prolonged hospital stays and an increased use of health resources. Fosfomycin is a broad-spectrum antibiotic discovered in 1969 that remains susceptible to a large number of organisms due to its low international use. Fosfomycin can be prepared as an oral solution with an orange/tangerine flavour and is currently approved for use in females \>12 years old. Despite extensive evidence of its efficacy in adults and safety in neonates, the use of fosfomycin in children remains limited and fosfomycin is not currently licensed for use in children \<12 years old in Australia. The aim of this clinical trial is to compare the use of oral fosfomycin against standard of care antibiotics for the treatment of antibiotic resistant urinary tract infections in children. The main questions the trial aims to answer are: 1. Is oral fosfomycin non-inferior in efficacy to the current standard of care for the treatment of antibiotic-resistant urinary tract infections in children? 2. Is oral fosfomycin a safe and well-tolerated antibiotic in children? 3. What is the best dosing regimen of oral fosfomycin for the treatment of antibiotic-resistant UTIs in children?

2023-08-02

2027-08-01

2027-08-01

Recruiting

Early phase I

300

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomised controlled trial with an intervention arm and an active control arm (standard-of care)', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'Open-label study. Statisticians will be blind to groups when analysing results'}}, 'enrollmentInfo': {'count': 300, 'type': 'ESTIMATED'}}

2024-06-06