Study design:
An open label, multi-centre, pragmatic, non-inferiority randomised controlled trial (RCT).
It will incorporate a two-arm, non-inferiority design with parallel groups and 1:1 allocation of children with ≥2 complicated features of UTI presenting to the ED in whom clinicians deem parenteral antibiotics are required.
Primary objective:
The primary objective of this trial is to compare whether 1 dose of a daily parenteral antibiotic followed by 2 days oral antibiotics is as clinically effective (non-inferior) in resolving UTI symptoms at 72 hours after the first IV dose, as 3 doses of a daily parenteral antibiotic for complicated urinary tract infections presenting to the ED.
Definition:
1 dose: one dose of a daily dose IV to cover Gram negative bacteria +/- one dose IV to cover Enterococcus spp. This will be followed by two days oral antibiotics.
3 doses: three doses of a daily dose IV to cover Gram negative bacteria +/- 3 days IV antibiotics to cover Enterococcus spp.
Secondary objectives:
The secondary objectives of this trial are to compare the following outcomes between the 1 dose and the 3 doses arms:
* Readmission due to persistent fever, vomiting, rigors, or clinical deterioration (e.g., poor feeding, dehydration) within 14 days of the initial dose of IV antibiotics.
* Readmission due to persistent fever, vomiting, rigors, or clinical deterioration (e.g., poor feeding, dehydration) within 1 month of the initial dose of IV antibiotics.
* Transfer from HITH/ambulatory care to ward care during admission within 72 hours of the initial dose of IV antibiotics.
* Time to resolution of fever/vomiting/rigors within 72 hours of the initial dose of IV antibiotics as reported by parents/guardian.
* Improvement as determined by parents/guardian at 72 hours after the first IV dose.
* Antiemetic use for 72 hours from the initial IV antibiotic dose.
* Duration of IV antibiotics (actually received by patient) from the first dose of IV antibiotics to last dose of IV antibiotics.
* Duration of oral antibiotics (actually received by patient) from the first dose of oral antibiotics (after IV antibiotics started) to last dose of IV antibiotics.
* Total duration of antibiotics: sum of duration of IV antibiotics and oral antibiotics.
* Recurrence of UTI within 14 days from the first dose of IV antibiotics.
* Recurrence of UTI within 1 month from the first dose of IV antibiotics.
* Complications of UTI from the initial IV antibiotics dose to 14 days after the initial dose.
* Adverse events from the initial IV antibiotics dose to 14 days after the initial dose.
* Quality of life (QoL) indicators on Day 1 of IV antibiotics (within 24 hours of initial IV antibiotics) and after Day 4 (72 hours up to Day 7).
* Parental QoL on Day 14.
* Cost-effectiveness - hospital administrative data on costs and patient/parents reported costs.
* Follow up microbiological urine culture after commencing IV antibiotics.
* Imaging reports - ultrasound or other imaging results will be collected for patients who have them performed.
Intervention:
Patients who are eligible for the study will be randomised to receive 1 dose of daily IV antibiotics followed by 2 days of oral antibiotics or 3 doses of daily IV antibiotics . All participants will receive a total of 7 days treatment with antibiotics for the complicated urinary tract infection.
Oral antibiotics will start as soon as able to tolerate, within 12 hours of the last IV dose for both arms.
Study methodology:
Enrolment and randomisation: During ED assessment, clinicians will identify patients with a suspected UTI and screen patients against eligibility criteria. The relevant clinical team at each site will receive standardized, study specific education based on centrally developed study education materials. Presence of the following symptoms/sign will be recorded at baseline (fever, vomiting, rigors, tachycardia). Participants will be randomised to one of the 2 arms after written informed consent is obtained.
Intervention Day 1:
The first dose of the antibiotics will be commenced in the ED. Care of the patient will be as per routine clinical care. Decision for admission to hospital and location of treatment (ambulatory/Hospital-in-the-Home care) will be determined by the treating clinician as per routine clinical care. Parents will be provided with a thermometer and a diary to record a daily assessment of their child (fever, rigors, vomiting).
Intervention Day 4 :
72 hours after the first dose of IV antibiotics, a research nurse/assistant will conduct an assessment over phone or telehealth to obtain the primary outcome data: Persistence of baseline symptoms (fever, vomiting, rigors) or development of these symptoms (if not previously present) since baseline. Any ambiguity with regards to symptoms being attributable to UTI will be judged by a blinded clinician external to the research team.
Follow up Day 14:
14 days after the first dose of IV antibiotics, a research nurse/assistant will conduct an assessment over phone or telehealth for follow up data including whether GP/ED visit or readmission occurred for UTI and total duration of antibiotics taken by the patient.
Follow up 1 month:
1 month after the first dose of IV antibiotics, a research nurse/assistant will conduct an assessment over phone or telehealth for follow up data including whether GP/ED visit or readmission occurred for UTI, total duration of antibiotics taken by the patient.
