Ignite Creation Date:
2024-05-06 @ 6:34 PM
Last Modification Date:
2024-10-26 @ 2:50 PM
Study NCT ID:
NCT05709028
Status:
RECRUITING
Last Update Posted:
2024-06-06
First Post:
2023-01-23
Brief Title:
Fosfomycin Versus Standard of Care in Children With Antibiotic-resistant Urinary Tract Infections
Sponsor:
University of Sydney
Organization:
University of Sydney
Study Overview
Official 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
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FosUTI
Brief Summary:
Urinary tract infections UTIs are among the most common bacterial infections in children Up to 50 of UTIs are caused by multi-drug resistant ESBL-producing gram negative bacteria that do not respond to treatment with oral penicillins 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 orangetangerine 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
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
Detailed Description:
This is a Phase 3 non-inferior pragmatic multi-centre adaptive randomised clinical trial
Up to 300 participants aged 6 months to 18 years of age with a clinical and microbiological diagnosis of an antibiotic-resistant urinary tract infection will be recruited for the trial Children will be randomised 11 to receive either oral fosfomycin the intervention or standard of care The duration of antibiotic treatment will be dependent on whether the childs UTI is complicated or uncomplicated Children with at least two of the following signs and symptoms will meet criteria of having a complicated UTI fever nausea or vomiting other signs or symptoms of systemic illness including chilld or rigors significant fatigue irritability or malaise above baseline flank or back pain ultrasound findings suggestive of an upper renal tract infection a known history of structural andor mechanical urological abnormalities patients with a stent in situ or known renal tract calculi patients who are immunocompromised Children who do not meet the criteria for a complicated UTI will meet criteria for an uncomplicated UTI
For children allocated to the standard of care SC arm the choice of antibiotic will be as per physician preference based on institutional prescribing practices local antibiograms and medication availability Children with an uncomplicated UTI will be prescribed a 3-day course of SOC antibiotics Then on Day 3 either a Stop if the child has clinically improved or b Give an additional 48 hours of SOC antibiotics if the child has ongoing fever or clinical symptoms consistent with an uncomplicated UTI or c 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 with a complicated UTI diagnosis at the time of enrolment will be administered a total 10-day course of SOC antibiotics
For children allocated to the intervention arm Children with an uncomplicated UTI will be administered a single dose of oral fosfomycin trometamol Then on Day 2 either a Stop if the child has clinically improved or b Give an additional dose of oral fosfomycin trometamol if the child has ongoing fever or clinical symptoms consistent with an uncomplicated UTI or c 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 with a complicated UTI diagnosis at the time of enrolment will be administered a total 10-day course of oral fosfomycin trometamol with repeat doses administered every 48 hours
Children enrolled into the oral fosfomycin group as well as children enrolled in the standard of care group who receive an oral antibiotic will be asked to complete a tolerability questionnaire following the first dose of the oral antibiotic The childs parent and a member of their clinical team will also complete this questionnaire All examinations investigations and clinical interventions during the study period will be tailored to the childs needs as per routine standard of care Clinical observations and results will be recorded on a case report form and entered into a secure electronic database At Day 3 10 and 28 after enrolment parents will receive an SMS questionnaire to monitor their ongoing health capture adverse events andor capture their medication adherence
50 children aged 6 months to 12 who have been randomised to the fosfomycin arm will be co-enrolled in a pharmacokinetic sub-study For these children two blood samples will be taken within 24 hours after the first dose of fosfomycin to determine the plasma fosfomycin concentrations Co-enrolment into the pharmacokinetic sub-study is optional and will only be performed at a subset of study sites
Up to 300 participants aged 6 months to 18 years of age with a clinical and microbiological diagnosis of an antibiotic-resistant urinary tract infection will be recruited for the trial Children will be randomised 11 to receive either oral fosfomycin the intervention or standard of care The duration of antibiotic treatment will be dependent on whether the childs UTI is complicated or uncomplicated Children with at least two of the following signs and symptoms will meet criteria of having a complicated UTI fever nausea or vomiting other signs or symptoms of systemic illness including chilld or rigors significant fatigue irritability or malaise above baseline flank or back pain ultrasound findings suggestive of an upper renal tract infection a known history of structural andor mechanical urological abnormalities patients with a stent in situ or known renal tract calculi patients who are immunocompromised Children who do not meet the criteria for a complicated UTI will meet criteria for an uncomplicated UTI
For children allocated to the standard of care SC arm the choice of antibiotic will be as per physician preference based on institutional prescribing practices local antibiograms and medication availability Children with an uncomplicated UTI will be prescribed a 3-day course of SOC antibiotics Then on Day 3 either a Stop if the child has clinically improved or b Give an additional 48 hours of SOC antibiotics if the child has ongoing fever or clinical symptoms consistent with an uncomplicated UTI or c 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 with a complicated UTI diagnosis at the time of enrolment will be administered a total 10-day course of SOC antibiotics
For children allocated to the intervention arm Children with an uncomplicated UTI will be administered a single dose of oral fosfomycin trometamol Then on Day 2 either a Stop if the child has clinically improved or b Give an additional dose of oral fosfomycin trometamol if the child has ongoing fever or clinical symptoms consistent with an uncomplicated UTI or c 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 with a complicated UTI diagnosis at the time of enrolment will be administered a total 10-day course of oral fosfomycin trometamol with repeat doses administered every 48 hours
Children enrolled into the oral fosfomycin group as well as children enrolled in the standard of care group who receive an oral antibiotic will be asked to complete a tolerability questionnaire following the first dose of the oral antibiotic The childs parent and a member of their clinical team will also complete this questionnaire All examinations investigations and clinical interventions during the study period will be tailored to the childs needs as per routine standard of care Clinical observations and results will be recorded on a case report form and entered into a secure electronic database At Day 3 10 and 28 after enrolment parents will receive an SMS questionnaire to monitor their ongoing health capture adverse events andor capture their medication adherence
50 children aged 6 months to 12 who have been randomised to the fosfomycin arm will be co-enrolled in a pharmacokinetic sub-study For these children two blood samples will be taken within 24 hours after the first dose of fosfomycin to determine the plasma fosfomycin concentrations Co-enrolment into the pharmacokinetic sub-study is optional and will only be performed at a subset of study sites
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None