Single Dose Intravenous Antibiotics for Complicated Urinary Tract Infections in Children

NCT04876131 | Recruiting Phase 4 DMC

• 1 other identifier: 72065
• Study Type: interventional
• Target: 452
• Locations: 2 countries
• Sites: 6

Brief Summary

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.

Conditions

Complicated Urinary Tract Infection; Infection; Pediatric Infectious Disease

Outcome Measures

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.

  72 hours

Secondary Outcomes (19)

• 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.

  14 days

• 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

  1 month

• 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.

  72 hours

• Risk difference between 1 dose and 3 doses IV in the proportion of participants with parental reported improvement

  72 hours

• Mean difference between 1 dose and 3 doses IV in duration of IV antibiotics usage

  7 days

Study Arms (2)

Arm 1, 1 dose

EXPERIMENTAL

* Single dose IV to cover Gram negative bacteria followed by 2 days of oral antibiotics * Single dose IV to cover Enterococcus spp IV antibiotics are as per local institutional guidelines and microbiology eg: IV gentamicin with or without IV benzylpenicillin. Gentamicin is used when Gram Negative coverage is appropriate, benzylpenicillin is also used when Enterococcus coverage is appropriate, depending on local microbiology data. Once the IV component is complete the patient will be given an oral antibiotic (cefalexin) on day 2 and 3 of the study.

Drug: Benzylpenicillin - single dose; Drug: Gentamicin - single dose; Drug: Cefalexin - post single dose of IV antibiotics for the remaining two days

Arm 2, 3 doses

ACTIVE COMPARATOR

* 3 doses IV to cover Gram negative bacteria * 3 days IV antibiotics to cover Enterococcus spp IV antibiotics are as per local institutional guidelines and microbiology eg: IV gentamicin with or without IV benzylpenicillin. Gentamicin is used when Gram Negative coverage is appropriate, benzylpenicillin is also used when Enterococcus coverage is appropriate, depending on local microbiology data.

Drug: Benzylpenicillin - three days; Drug: Gentamicin - three days

Interventions

Benzylpenicillin - single dose DRUG

Participants 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.

Arm 1, 1 dose

Benzylpenicillin - three days DRUG

Participants 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.

Arm 2, 3 doses

Gentamicin - single dose DRUG

Participants 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)

Arm 1, 1 dose

Gentamicin - three days DRUG

Participants 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)

Arm 2, 3 doses

Cefalexin - post single dose of IV antibiotics for the remaining two days DRUG

Oral 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

Arm 1, 1 dose

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).
• Abnormal urinary dipstick leucocyte esterase \>1+ or nitrite positive OR ≥5 White Blood Cells (WBCs) per high-power field in centrifuged urine OR≥ 10 White Blood Cells (WBCs) per mm3 in uncentrifuged urine and bacteriuria with any bacteria per high-power field
• ED clinician determines the child requires treatment with IV antibiotics \* In ED, only urine dipstick or urinalysis will be available. Once urine culture is available, to be included in the efficacy analysis, culture results must meet the following criteria: Positive urine culture result with no more than 2 species of microorganisms AND Spontaneously voided urine with ≥105 microorganisms per mL of urine or Suprapubic aspirate or urinary catheter with ≥104 microorganisms per mL of urine. In the absence of a positive urine culture, ultrasonographic findings supporting pyelonephritis (per reporting radiologist) will be accepted as evidence of a urinary tract infection.

You may not qualify if:

• 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
• Unrepaired posterior urethral valves
• Indwelling stent and fever
• Previously enrolled participants in the CHOICE UTI trial.
• Previous IV antibiotics for same UTI episode eg interhospital transfer whereby significant time has passed since first dose IV
• Patients with clinically suspected renal abscess e.g., extreme renal tenderness, out of keeping with pyelonephritis (clinically determined).
• Clinician does not intend on prescribing a course of IV antibiotics but plans on only giving a single dose from the outset
• Recurrence of urinary tract infection within 2 weeks
• Unable to obtain consent
• Patient is pregnant

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• Royal Children's Hospital: collaborator

Study Sites (6)

Women and Children's Hospital

Adelaide, South Australia, Australia

RECRUITING

University Hospital Geelong

Geelong, Victoria, 3220, Australia

RECRUITING

Monash Health

Melbourne, Victoria, 3168, Australia

RECRUITING

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

RECRUITING

Perth Children's Hospital

Perth, Washington, 6009, Australia

RECRUITING

Starship Children's Hospital

Auckland, Auckland Province, 1023, New Zealand

RECRUITING

MeSH Terms

Conditions

Infections

Interventions

Penicillin G; Gentamicins; Anti-Bacterial Agents

Intervention Hierarchy (Ancestors)

Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Laila Ibrahim

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

• Penelope Bryant

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laila Ibrahim

CONTACT

+61401765546; laila.ibrahim@mcri.edu.au

Lucy Hill

CONTACT

+61383416200; lucy.hill@mcri.edu.au

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be recruited when they present to the emergency department with a complicated UTI. Once they have been consented to the study they will then be randomised into one of the treatment arms, these treatment arms will run parallel to one another.

Study Record Dates

• First Submitted: May 2, 2021
• First Posted: May 6, 2021
• Study Start: May 30, 2022
• Primary Completion (Estimated): May 16, 2028
• Study Completion (Estimated): May 16, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 6 months after publication of primary outcome
• Access Criteria: Prior to this data being made available a data access agreement much be signed between the relevant parties and approval by the trial steering committee. Data will only be shared with recognised research institutions

Locations

NZ (1); AU (5)