Single Dose Intravenous Antibiotics for Complicated Urinary Tract Infections in Children
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age3-18
SponsorMurdoch Childrens Research Institute
About this trial
Urinary tract infections (UTI) are commonly encountered in children, with 7% diagnosed with at least one UTI by the age of 19 years. The evidence for treatment of uncomplicated UTI is clear; oral antibiotics are as good as intravenous (IV) antibiotics, usually for a total of 7 days. Complicated UTIs (cUTIs) on the other hand, are common reasons for hospital admissions for IV antibiotics and constitute a major burden for healthcare systems. There is considerable variation in care for children who present with UTI and have complicating features such as vomiting, dehydration, urological abnormalities or have a previous history of UTI. Australian and international guidelines lack clear, evidence-based recommendations to guide treatment in this group. Without gold standard evidence, these children will continue to receive unnecessary IV antibiotics, longer hospital stays and poorer health outcomes.
This multicentre, non-inferiority randomised trial will investigate if One dose - single dose of IV followed by 2 days oral antibiotics is as non-inferior to Three doses for children with UTI and co-existing complicating factors presenting to the Emergency Department (ED). In other words, this study will compare if a single dose of IV antibiotics plus two days oral antibiotics is as clinically effective as 3 doses antibiotics in resolving UTI symptoms at 72 hours after the first dose of IV antibiotics, for complicated UTIs in children presenting to the ED. All participants will receive a total of 7 days of antibiotics for the complicated urinary tract infection. If 1 dose IV and 2 days oral antibiotics is found to be as good as 3 days, the duration of IV antibiotics for complicated UTI can be reduced along with avoidance of the inherent risks of unnecessary hospital admission by administering a single IV dose in an outpatient/ED setting. On the other hand if a single IV dose results in prolonged symptoms or treatment failure, this will inform practice for the proportion of children who have a single dose of IV antibiotics in the ED and are sent home on oral antibiotics. Regardless of the outcome, this trial will inform clinical practice for complicated UTI to improve health outcomes for this group.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
3 months (corrected age) to 18 years
Fever (reported fever at home or measured fever of ≥38 degrees Celsius associated with the illness that triggered current ED presentation (eg fever may have been 18 hours prior to presentation but none since then because patient has been on maximal antipyretics - paracetamol or ibuprofen)
Any of the following complicating features: Vomiting, Rigors, History of recurrent UTI, Urological abnormalities, Tachycardia
Urine sample available (Urine culture must have been collected prior to or within an hour of antibiotic treatment, either at the GP or ED - in order to assess urine culture as per below).
Disqualifiers
Sepsis (requiring inotropic support or more than 20ml/kg of fluid bolus in Emergency Department)
Known allergy to all once daily study drug options (gentamicin or ceftriaxone or amikacin)
If the patient has another co-existing condition which requires (based on established evidence-based guidelines) more than 1 dose of IV antibiotics eg meningitis
Known chronic renal failure or renal transplant patients
Trial design
Design model
Parallel
Treatments tested in this trial
Benzylpenicillin - single dose
DrugParticipants will receive a single dose of IV antibiotic (benzylpenicillin). Benzylpenicillin dosing: 1 month - 18 years, IV or Intramuscular (IM) 30 mg/kg (maximum 1.2 g) every 6 hours.
Benzylpenicillin - three days
DrugParticipants will receive three days of this IV antibiotic (benzylpenicillin). Benzylpenicillin dosing: 1 month - 18 years, IV or Intramuscular (IM) 30 mg/kg (maximum 1.2 g) every 6 hours. For severe infections, use up to 60 mg/kg (maximum 2.4 g) every 4-6 hours.
Gentamicin - single dose
DrugParticipants will receive a single dose of IV antibiotic (gentamicin). Gentamicin dosing: Children ≤10 years old: 7.5 mg/kg (maximum dose 320 mg) Children \>10 years old: 6-7 mg/kg (maximum dose 560 mg)
Gentamicin - three days
DrugParticipants will receive three days of this IV antibiotic (gentamicin). Gentamicin dosing: Children ≤10 years old: 7.5 mg/kg (maximum dose 320 mg) Children \>10 years old: 6-7 mg/kg (maximum dose 560 mg)
Cefalexin - post single dose of IV antibiotics for the remaining two days
DrugOral antibiotic will be as per local guidelines. i.e. Cefalexin 25mg/kg (maximum dosage 500mg) 4 times a day or 33mg/kg (maximum dosage 500mg) 3 times a day
Treatment groups
396 Participants
are divided into 2 treatment groupsGroup A: Arm 1, 1 doseExperimental treatment 3 interventions
Group B: Arm 2, 3 dosesActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Risk difference between 1 dose and 3 doses IV in the proportion of participants with clinical failure at 72 hours
Clinical failure is defined as persistence of baseline symptoms (fever, vomiting or rigors) or development of new symptoms (fever, vomiting or rigors) attributable to UTI at 72 hours. Assessment of clinical failure to be conducted at least 6 hours after antipyretic. Presence of fever, vomiting, or rigors reported by parents within 6 hours of assessment will be recorded as present at assessment.
Time frame
72 hoursSecondary outcomes
1
Risk difference between 1 dose and 3 doses IV in the proportion of participants readmitted or attending the ED within 14 days of the initial dose of IV antibiotic.
Proportion of readmissions within 14 days of the initial dose of IV antibiotics due to persistent fever, vomiting, rigors, or clinical deterioration (eg poor feeding, dehydration) that can be attributable to the UTI
Time frame
14 days2
Risk difference between 1 dose and 3 doses IV in the proportion of participants readmitted or attending the ED within 1 month of the initial dose of IV antibiotics
Proportion of readmission within 1 month of the initial dose of IV antibiotics due to persistent fever, vomiting, rigors, or clinical deterioration (eg poor feeding, dehydration) that can be attributable to the UTI.
Time frame
1 month3
Risk difference between 1 dose and 3 doses IV in proportion of participants transferred from HITH or ambulatory care to ward care within 72 hours of initial dose of IV antibiotics.
Proportions of participants transferred from HITH or ambulatory care to ward care within 72 hours of initial dose of IV antibiotics.
Time frame
72 hours4
Risk difference between 1 dose and 3 doses IV in the proportion of participants with parental reported improvement
Proportion of patients who are reported as 'generally improved/better' at 72 hours of the initial IV antibiotic dose. This will be reported via the daily diary completed by the parent on day 1, 2 and 3.
Time frame
72 hoursSponsors and contacts
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Murdoch Childrens Research Institute
Lead sponsor
Royal Children's Hospital
Collaborator
Source ClinicalTrials.gov