Bone InfectionPhase 4BESTNCT04538053
BonE and Joint Infections - Simplifying Treatment in Children Trial
A Phase 4 study testing Oral cefalexin only and IV cefazolin or IV flucloxacillin followed by oral cefalexin in people with Bone Infection and Septic Arthritis, run by Murdoch Childrens Research Institute at 11 sites in 3 countries.
Trial summary
This is a multi- centre trial of children with bone and joint infections (BJIs) at eleven major paediatric hospitals in Australia, New Zealand and Ireland. The primary objective is to establish if in children with acute, uncomplicated BJIs, entirely oral antibiotic treatment is not inferior to initial intravenous (IV)… Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Bone Infection, Septic Arthritis, Bone and Joint Infection
- What is being tested?
- Oral cefalexin only and IV cefazolin or IV flucloxacillin followed by oral cefalexin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 214 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 1 Jun 2021to Feb 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children aged 1 to 18 years with acute, uncomplicated, uncomplicated, haematogenous osteomyelitis or septic arthritis
- Symptoms are present for ≤10 days
- Osteomyelitis (OM): involvement of long bones of arm or leg AND either pain, point tenderness upon palpation of bone or joint, or difficulty weight bearing; OR Septic arthritis (SA): any of painful and/or swollen large joint; restriction of joint movement; tenderness or warmth. Those with both SA and OM at the same site as the current infection are also eligible.
- The participant has an elevated C-reactive protein (CRP) ≥20 mg/L or erythrocyte sedimentation rate (ESR) ≥10 mm/h
Who cannot join
- Infection due to bacteria resistant to cefalexin or atypical infection (e.g. mycobacterial, fungal)
- Features of sepsis as defined by the presence of organ dysfunction (defined using definitions within the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score)
- Concomitant severe, invasive infection e.g. necrotising fasciitis
- Complicated infection (e.g. presence of prosthetic material; large subperiosteal or intraosseous (either >3 mm) abscess or soft tissue abscess without surgical intervention; infection secondary to or complicated by trauma)
- History of allergy to cephalosporin antibiotics or immediate, severe reaction to penicillins
- Received more than four IV or oral doses of an antibiotic with activity against the likely bacteria causing the current infection
Show all 10Show fewer
- Prior episode of osteomyelitis (OM) or septic arthritis (SA) of the same site
- Prior condition predisposing to poor absorption (e.g. inflammatory bowel disease, current gastrointestinal symptoms) or complicated disease (e.g. immunodeficiency)
- Prior enrolment in the trial
- Current recipient of another investigational product as part of a clinical trial
Trial locations and contacts
11 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
11 sites in 3 countries
Australia9 sites, 8 recruiting
- Recruiting
Women's and Children's Hospital
Adelaide, South Australia, 5006
Celia M Cooper, Dr, (08)81616396, celia.cooper@sa.gov.au
Nicole Williams, A/Prof
- Recruiting
Queensland Children's Hospital
Brisbane, Queensland, 4101
Clare Nourse, Prof, 0413586954, clare.nourse@health.qld.gov.au
Philip Britton, Dr
- Recruiting
Royal Darwin Hospital
Darwin, Northern Territory, 0811
Joshua R Francis, +61423528381, josh.francis@menzies.edu.au
Joshua Francis, Prof
- Recruiting
Nepean Hospital
Kingswood, New South Wales, 2747
Archana Koirala, Dr, 0430112042, archana.koirala@health.nsw.gov.au
Archana Koirala, Dr
- Recruiting
The Royal Children's Hospital
Melbourne, Victoria, 3051
Alison Boast, MD, +61395699551, alison.boast@rch.org.au
Amanda Gwee, PhD, +61395699551, amanda.gwee@rch.org.au
- Recruiting
John Hunter Children's Hospital
New Lambton Heights, New South Wales, 2305
Coen Butters, Dr, +61 2 4291 3000, Coen.Butters@health.nsw.gov.au
Coen Butters, Dr
- Recruiting
Perth Children's Hospital
Perth, Washington, 6009
Asha Bowen, A/Prof, 08 64562222, asha.bowen@health.wa.gov.au
Asha Bowen, Prof
- Recruiting
Sydney Children's Hospital Network
Sydney, New South Wales, 2031
Brendan Mcmullan, Dr, 293821241, Brendan.Mcmullan@health.nsw.gov.au
Brendan McMullan, Dr
- Active, not recruiting
The Children's Hospital at Westmead
Sydney, New South Wales, 2145
Ireland1 site, 1 recruiting
- Not yet recruiting
Children's Health Ireland
Dublin
Bridget Freyne, Dr, +353894573080, bridget.freyne@ucd.ie
Bridget Freyne, Dr
New Zealand1 site, 1 recruiting
- Recruiting
Christchurch Hospital
Christchurch, 8011
Tony Walls, A/Prof, tony.walls@otago.ac.nz
Tony Walls, A/Prof
About this study
This is a multi- centre trial of children with bone and joint infections (BJIs) at eleven major paediatric hospitals in Australia, New Zealand and Ireland. The primary objective is to establish if in children with acute, uncomplicated BJIs, entirely oral antibiotic treatment is not inferior to initial intravenous (IV) treatment for 1 to 7 days followed by an oral antibiotic course in achieving full recovery 3 months after presentation. Children will be randomly allocated to the 'entirely oral antibiotic' group or the 'standard treatment' group.
Read the detailed description
Children with acute onset BJIs who present to the participating sites will be enrolled into the trial if eligible (see eligibility criteria) and randomly allocated into one of the two groups. Children in the 'standard treatment group' will receive standard treatment for BJIs, which consists of IV antibiotics for 1-7 days followed by 3 weeks of oral antibiotics. Children in the 'entirely oral treatment group' will receive high dose oral antibiotics, followed by the standard dose of oral antibiotics for 3 weeks. The outcomes of children in each of the two groups will be compared to determine whether BJIs can be treated without needing a course of IV antibiotics.
- Being tested
- Oral cefalexin only, IV cefazolin or IV flucloxacillin followed by oral cefalexin
- Medical subject headings
- Arthritis, Infectious, Osteomyelitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral cefalexin onlyDrug
High-dose oral cefalexin
IV cefazolin or IV flucloxacillin followed by oral cefalexinDrug
Standard therapy of IV cefazolin or IV flucloxacillin followed by high dose oral cefalexin
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | Children will receive high-dose oral cefalexin 37.5 mg/kg/dose (max 1.5 g) four-times daily (QID) for 1 to 7 days followed by oral cefalexin 45 mg/kg/dose (max 1.5 g) TDS for a total course of 3 weeks Receives: Drug: Oral cefalexin only |
| Standard Therapy | Active comparator | Children will receive IV cefazolin 50 mg/kg/dose (max 2 g) three-times daily (TDS) or IV flucloxacillin 50 mg/kg/dose (max 2 g) QID for 1 to 7 days followed by oral cefalexin 45 mg/kg/dose (max 1.5 g) TDS for a total course of 3 weeks Receives: Drug: IV cefazolin or IV flucloxacillin followed by oral cefalexin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of children assessed as having made a full recovery 3 months after presentation by an independent committee
Full recovery is defined by the absence of:
(i) Clinical features of osteomyelitis or septic arthritis (ii) No episodes of disease recurrence (symptoms and signs of infection at the same site) requiring further antibiotic administration after cessation of initial treatment.
Children will be assessed by an independent specialist paediatrician.
The independent committee will include an orthopaedic surgeon, general paediatrician and infectious diseases physician, who will review the patient record and will be blinded to the initial trial assignment.
Measured: 3 months
Secondary outcomes (11)
Proportion of children with recurrent disease at 6 months.
Proportion of children with recurrence of symptoms and signs of infection at the same site after initial recovery and cessation of initial antibiotic treatment requiring further antibiotic administration, assessed by review of medical records and phone review at 6 months.
Measured: 6 months
Proportion of children with recurrent disease at 12 months.
Proportion of children with recurrence of symptoms and signs of infection at the same site after initial recovery and cessation of initial antibiotic treatment requiring further antibiotic administration, assessed by treating team at 12 months.
Measured: 12 months
Proportion of children with complications of their disease at 3 months.
Complications assessed by an independent paediatrician at 3 months, defined as:
(i) residual dysfunction (ii) pain
Measured: 3 months
Proportion of children with complications of their disease at 12 months.
Complications assessed by treating team at 12 months defined as:
(i) residual dysfunction (ii) osteonecrosis (iii) pain (iv) growth arrest (v) limb deformity (vi) number of surgeries
An independent committee including an orthopaedic surgeon, general paediatrician and infectious diseases physician blinded to the initial trial assignment will review patient record at 3 and 12 months to assess secondary outcomes.
Measured: 12 months
Proportion of children with treatment-related adverse effects (AEs).
Adverse effects assessed between days 1-7 including:
(i) Complications of IV access (eg need for replacement, infection, extravasation, drug side effects); or (ii) high-dose oral antibiotics (eg. drug side effects, inability to tolerate the full dose)
Measured: Between Day 1-7
Quality of life - Pediatric Quality of Life Inventory (PedsQL)
The PedsQL (Pediatric Quality of Life Inventory) Generic Core Scale assesses health-related quality of life across physical, emotional, social and school functioning. This inventory includes 23 items and will be self-completed by the child (or proxy completed for younger children) at 3 months. A Total Scale Score is calculated and ranges from 0 to 100, with higher scores indicating better health-related quality of life.
Measured: 3 months
Changes in quality of life - Child Health Utility Scale (CHU9D)
The Child Health Utility 9D (CHU9D) is a paediatric generic preference-based measure of health-related quality of life. It consists of a short questionnaire and a set of preference weights based on general population values. The questionnaire comprises 9 questions, each with 5 response levels. The CHU9D will be completed between Day 8 and Day 14 and at 12 months by the child, or by a parent/caregiver as a proxy for younger children. CHU9D responses are converted into a preference-based utility score using an established scoring algorithm. Utility scores are anchored at 1 for full health and 0 for dead, with higher scores indicating better health-related quality of life.
Measured: Day 8 through to Day 14 (once), and 12 months
Quality of life - EQ-5D
EQ-5D (EuroQol Five-Dimension) is a generic measure of health-related quality of life. It assesses health across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses can be converted into a single health utility value using established population-based preference weights. Utility values are anchored at 1 for full health and 0 for dead, with values below 0 representing health states considered worse than dead. Higher values indicate better health-related quality of life. The questionnaire will be completed by the participant's parent/guardian, reflecting their own health, at any time between Day 8 and Day 14.
Measured: Once between Day 8 to Day 14
Changes in cost effectiveness
The incremental cost-effectiveness ratio will be determined. Estimated total sum of all hospital and participant/family resources required per participant per treatment course (AUD) collected using a standard questionnaire completed by the parent/ guardian once between Days 8 to 14 and then at 3 months.
Measured: Day 8 through Day 14 (once) and 3 months
Treatment adherence - Medication Adherence Response Scale
Measured by Medication Adherence Response Scale (MARS), completed between week 2-4 (end of treatment).The MARS employs a Yes/No response format, producing a total score ranging from 0 to 10, with higher scores indicating better adherence.
Measured: Between Week 2 to 4
Precise cefalexin dose required to optimise treatment of Bone and Joint Infections
Population pharmacokinetic-pharmacodynamic modelling will be used to simulate the optimal cefalexin level.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2020
- Study start1 Jun 2021
- Primary completionMar 2027 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bone InfectionStudies of the same condition, open and under way.
- More trials run by Murdoch Childrens Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 214 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Murdoch Childrens Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Amanda Gwee, PhD, Principal investigator, Murdoch Childrens Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04538053
- Sponsor's protocol ID
- 2019.287
- Acronym
- BEST
- Status last verified
- Oct 2026
- First submitted
- 14 Jul 2020
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The de-identified data set collected for this analysis of the BEST trial will be available six months after publication of the primary outcome. The study protocol, analysis plan and consent forms will also be available. The data may be obtained from the Murdoch Children's Research Institute by emailing amanda.gwee@rch.org.au
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BonE and Joint Infections - Simplifying Treatment in Children Trial
- ClinicalTrials.gov ID
- NCT04538053
- Acronym / sponsor ID
- BEST / 2019.287
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 214 participants (estimated)
- Lead sponsor
- Murdoch Childrens Research InstituteUniversity, hospital or other
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Feb 2028 (estimated)
- First posted
- 3 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi- centre trial of children with bone and joint infections (BJIs) at eleven major paediatric hospitals in Australia, New Zealand and Ireland. The primary objective is to establish if in children with acute, uncomplicated BJIs, entirely oral antibiotic treatment is not inferior to initial intravenous (IV) treatment for 1 to 7 days followed by an oral antibiotic course in achieving full recovery 3 months after presentation. Children will be randomly allocated to the 'entirely oral antibiotic' group or the 'standard treatment' group.
Detailed description
Children with acute onset BJIs who present to the participating sites will be enrolled into the trial if eligible (see eligibility criteria) and randomly allocated into one of the two groups. Children in the 'standard treatment group' will receive standard treatment for BJIs, which consists of IV antibiotics for 1-7 days followed by 3 weeks of oral antibiotics. Children in the 'entirely oral treatment group' will receive high dose oral antibiotics, followed by the standard dose of oral antibiotics for 3 weeks. The outcomes of children in each of the two groups will be compared to determine whether BJIs can be treated without needing a course of IV antibiotics.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Drug: Oral cefalexin onlyChildren will receive high-dose oral cefalexin 37.5 mg/kg/dose (max 1.5 g) four-times daily (QID) for 1 to 7 days followed by oral cefalexin 45 mg/kg/dose (max 1.5 g) TDS for a total course of 3 weeks |
| Standard Therapy | Active comparator | Drug: IV cefazolin or IV flucloxacillin followed by oral cefalexinChildren will receive IV cefazolin 50 mg/kg/dose (max 2 g) three-times daily (TDS) or IV flucloxacillin 50 mg/kg/dose (max 2 g) QID for 1 to 7 days followed by oral cefalexin 45 mg/kg/dose (max 1.5 g) TDS for a total course of 3 weeks |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Children aged 1 to 18 years with acute, uncomplicated, uncomplicated, haematogenous osteomyelitis or septic arthritis
- Symptoms are present for ≤10 days
- Osteomyelitis (OM): involvement of long bones of arm or leg AND either pain, point tenderness upon palpation of bone or joint, or difficulty weight bearing; OR Septic arthritis (SA): any of painful and/or swollen large joint; restriction of joint movement; tenderness or warmth. Those with both SA and OM at the same site as the current infection are also eligible.
- The participant has an elevated C-reactive protein (CRP) ≥20 mg/L or erythrocyte sedimentation rate (ESR) ≥10 mm/h
Key exclusion criteria (10 listed)
- Infection due to bacteria resistant to cefalexin or atypical infection (e.g. mycobacterial, fungal)
- Features of sepsis as defined by the presence of organ dysfunction (defined using definitions within the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score)
- Concomitant severe, invasive infection e.g. necrotising fasciitis
- Complicated infection (e.g. presence of prosthetic material; large subperiosteal or intraosseous (either >3 mm) abscess or soft tissue abscess without surgical intervention; infection secondary to or complicated by trauma)
- History of allergy to cephalosporin antibiotics or immediate, severe reaction to penicillins
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral cefalexin onlyHigh-dose oral cefalexin | Drug | Intervention |
| IV cefazolin or IV flucloxacillin followed by oral cefalexinStandard therapy of IV cefazolin or IV flucloxacillin followed by high dose oral cefalexin | Drug | Standard Therapy |
Primary outcome
Proportion of children assessed as having made a full recovery 3 months after presentation by an independent committee
Time frame: 3 months
Full recovery is defined by the absence of: (i) Clinical features of osteomyelitis or septic arthritis (ii) No episodes of disease recurrence (symptoms and signs of infection at the same site) requiring further antibiotic administration after cessation of initial treatment. Children will be assessed by an independent specialist paediatrician. The independent committee will include an orthopaedic surgeon, general paediatrician and infectious diseases physician, who will review the patient record and will be blinded to the initial trial assignment.
11 secondary outcomes
Proportion of children with recurrent disease at 6 months.
Time frame: 6 months
Proportion of children with recurrent disease at 12 months.
Time frame: 12 months
Proportion of children with complications of their disease at 3 months.
Time frame: 3 months
Proportion of children with complications of their disease at 12 months.
Time frame: 12 months
Proportion of children with treatment-related adverse effects (AEs).
Time frame: Between Day 1-7
Quality of life - Pediatric Quality of Life Inventory (PedsQL)
Time frame: 3 months
Changes in quality of life - Child Health Utility Scale (CHU9D)
Time frame: Day 8 through to Day 14 (once), and 12 months
Quality of life - EQ-5D
Time frame: Once between Day 8 to Day 14
Changes in cost effectiveness
Time frame: Day 8 through Day 14 (once) and 3 months
Treatment adherence - Medication Adherence Response Scale
Time frame: Between Week 2 to 4
Precise cefalexin dose required to optimise treatment of Bone and Joint Infections
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Individual participant dataSharing planned: Yes. The de-identified data set collected for this analysis of the BEST trial will be available six months after publication of the primary outcome. The study protocol, analysis plan and consent forms will also be available. The data may be obtained from the Murdoch Children's Research Institute by emailing amanda.gwee@rch.org.au
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Amanda Gwee, PhD principal investigator
Murdoch Childrens Research Institute
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oral cefalexin only and IV cefazolin or IV flucloxacillin followed by oral cefalexin in people with Bone Infection and Septic Arthritis, run by Murdoch Childrens Research Institute at 11 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Australia, Ireland, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alison Boast, MD (+61393455522, alison.boast@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of children assessed as having made a full recovery 3 months after presentation by an independent committee (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.