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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05709028




Registration number
NCT05709028
Ethics application status
Date submitted
23/01/2023
Date registered
1/02/2023

Titles & IDs
Public title
Fosfomycin Versus Standard of Care in Children With Antibiotic-resistant Urinary Tract Infections
Scientific title
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.
Secondary ID [1] 0 0
FosUTI
Universal Trial Number (UTN)
Trial acronym
FosUTI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Urinary Tract Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fosfomycin
Treatment: Drugs - Standard of care antibiotics

Experimental: Oral fosfomycin - * Children who have been diagnosed with an uncomplicated UTI will be administered a single dose of oral fosfomycin trometamol. Then, on Day 2 either;

1. Stop if the child has clinically improved, or
2. Give a second dose of oral fosfomycin trometamol if the child has ongoing fever or clinical symptoms consistent with an uncomplicated UTI, or
3. Give an additional 8 days of oral fosfomycin trometamol with repeat doses every 48 hours (to make up a total 10-day treatment duration) if the child has evidence of a complicated UTI.
* Children who have been diagnosed with a complicated UTI will be administered repeat doses of oral fosfomycin trometamol every 48 hours until the child has received a total 10-day course of antibiotics with presumed or proven efficacy against the urinary pathogen.

Active comparator: Standard of Care antibiotics - * Children who have been diagnosed with an uncomplicated UTI will be administered a 3-day course of standard of care (SOC) antibiotics with known efficacy against the urinary pathogen. Then, on Day 3 either;

1. Stop of the child has clinically improved, or
2. Give an additional 48 hours of SOC antibiotics if the child has ongoing fever or clinical symptoms consistent with an uncomplicated UTI, or
3. Give an additional 7 days of SOC antibiotics (to make up a total 10-day duration) if the child has evidence of a complicated UTI.
* Children who have been diagnosed with a complicated UTI will be administered a total 10-day course of SOC antibiotics with known efficacy against the urinary pathogen.


Treatment: Drugs: Fosfomycin
Fosfomycin trometamol is a white crystalline powder which is very soluble in water. The granules are mixed with 90ml of cool water for the constitution to dissolve and will be administered soon after reconstitution. Each 30ml will contain 1g fosfomycin base.

* Children = 6 months to \<1 year old will be administered 30ml (=1g fosfomycin base) of dissolved solution and the remainder discarded for each dose.
* Children = 1 to 11 years will be administered 60ml (=2g fosfomycin base) of dissolved solution and the remainder discarded for each dose.
* Children =12 and \<18 years will be administered the entire 90ml solution (= 3g fosfomycin base) for each dose.

Treatment: Drugs: Standard of care antibiotics
Standard of care antibiotics will be chosen by the treating clinician according to institutional prescribing practices, local antibiograms and medication availability.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Treatment failure within 28 days after enrolment between patients treated with standard of care versus oral fosfomycin.
Timepoint [1] 0 0
28 days
Secondary outcome [1] 0 0
Occurrence of treatment-related adverse events to Day 28
Timepoint [1] 0 0
28 days
Secondary outcome [2] 0 0
Occurrence of serious adverse events attributable to UTI to Day 28
Timepoint [2] 0 0
28 days
Secondary outcome [3] 0 0
Evidence of primary treatment failure, defined as: a) Persistent fever (>38.0C) attributable to UTI at 72h after enrolment; and/or b) Failure to return to baseline health at 28 days after enrolment
Timepoint [3] 0 0
28 days
Secondary outcome [4] 0 0
Evaluation of the cost of hospital resources in the first 28 days of enrolment in children receiving standard of care versus oral fosfomycin; including: a) Cost of prescribed drugs b) Cost of hospital services (inpatient and outpatient)
Timepoint [4] 0 0
28 days
Secondary outcome [5] 0 0
Assessment of the tolerability of oral antibiotic therapy in children, using a 5-point facial hedonic scale immediately after the first oral dose
Timepoint [5] 0 0
Day 1

Eligibility
Key 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.
Minimum age
6 Months
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2027
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Sydney Childrens Hospital - Sydney
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Sydney
Recruitment hospital [3] 0 0
Queensland Children's Hospital - Brisbane
Recruitment hospital [4] 0 0
Royal Childrens Hospital - Melbourne
Recruitment hospital [5] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
4101 - Brisbane
Recruitment postcode(s) [4] 0 0
3052 - Melbourne
Recruitment postcode(s) [5] 0 0
6000 - Perth

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Phoebe Williams
Address 0 0
University of Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Michelle L Harrison
Address 0 0
Country 0 0
Phone 0 0
0411900359
Fax 0 0
Email 0 0
m.harrison@sydney.edu.au
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Efficacy and AEs/SAEs will be summarised and pooled. Deidentified individual data will be shared with the DSMB and ethics for SAEs only.

Investigators have the protocols and the ICFs. SAP will be available for all investigators once authored. Reports and analytical code will be shared when approved by trial statisticians.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05709028