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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04538053




Registration number
NCT04538053
Ethics application status
Date submitted
14/07/2020
Date registered
3/09/2020
Date last updated
3/09/2020

Titles & IDs
Public title
BonE and Joint Infections - Simplifying Treatment in Children Trial
Scientific title
BonE and Joint Infections - Simplifying Treatment in Children Trial
Secondary ID [1] 0 0
2019.287
Universal Trial Number (UTN)
Trial acronym
BEST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bone Infection 0 0
Septic Arthritis 0 0
Bone and Joint Infection 0 0
Osteomyelitis 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Oral cefalexin only
Treatment: Drugs - IV cefazolin followed by oral cefalexin

Active Comparator: Intervention - Children will receive high-dose oral cefalexin 37.5 mg/kg/dose (max 1.5 g) four-times daily (QID) for 2 to 4 days followed by oral cefalexin 25 mg/kg/dose (max 1 g) QID for a total course of 3 weeks

Active Comparator: Standard Therapy - Children will receive IV cefazolin 50 mg/kg/dose (max 2 g) three-times daily (TDS) for 2 to 4 days followed by oral cefalexin 25 mg/kg/dose (max 1 g) four-times daily (QID) for a total course of 3 weeks


Treatment: Drugs: Oral cefalexin only
High-dose oral cefalexin

Treatment: Drugs: IV cefazolin followed by oral cefalexin
Standard therapy of IV cefazolin followed by high dose oral cefalexin

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of children assessed as having made a full recovery 3 months - Full recovery is defined by the absence of:
(i) Clinical features of osteomyelitis or septic arthritis (ii) No episodes of disease recurrence requiring further antibiotic administration after initial treatment.
Assessment made by a qualified paediatrician.
Timepoint [1] 0 0
3 months
Secondary outcome [1] 0 0
Proportion of children with with recurrent disease at 6 months. - Proportion of children with recurrence of symptoms and signs after initial recovery requiring further antibiotic administration assessed at 3 months by an independent committee.
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
Proportion of children with with recurrent disease at 12 months. - Proportion of children with recurrence of symptoms and signs after initial recovery requiring further antibiotic administration assessed at 12 months by an independent committee.
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
Proportion of children with complications of their disease at 3 months. - Complications assessed by an independent committee defined as:
(i) residual poor function (ii) bone death (osteonecrosis) (iii) pain (iv) growth arrest (v) limb deformity
Timepoint [3] 0 0
3 months
Secondary outcome [4] 0 0
Proportion of children with complications of their disease at 12 months. - Complications assessed by an independent committee defined as:
(i) residual poor function (ii) bone death (osteonecrosis) (iii) pain (iv) growth arrest (v) limb deformity
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Proportion of children with treatment-related adverse effects (AEs). - Adverse effects assessed between days 2 - 4 by an independent review committee including:
(i) complications of IV access (e.g. need for replacement, infection, extravasation, drug side effects); or (ii) high-dose oral antibiotics (e.g. drug side effects, inability to tolerate the full dose).
Timepoint [5] 0 0
Day 4
Secondary outcome [6] 0 0
Quality of life - Pediatric Quality of Life Inventory (PedsQL) Day 4 - Mean quality of life determined by PedsQL questionnaires administered between days 2 - 4 (while receiving initial IV or high-dose oral treatment) by the study team. The questionnaire will be asked of children if aged less over 7 years of age or the parent/guardian if the child is aged under 7 years of age.
PedsQL is an acronym for the Pediatric Quality of Life Inventory. This inventory includes 23 items each scored 0 to 5 . The minimum score is 0 and the maximum score is 92. Lower scores indicate better quality of life.
Timepoint [6] 0 0
Day 4
Secondary outcome [7] 0 0
Quality of life - Child Health Utility Scale (CHU9D) Day 4 - Mean quality of life determined by CHU9D questionnaires administered between days 2 - 4 (while receiving initial IV or high-dose oral treatment) by the study team. The questionnaire will be asked of children if aged less over 7 years of age or the parent/guardian if the child is aged under 7 years of age.
CHU9D is an acronym for the Child Health Utility scale. It includes 9 domains scored 0 to 5. The minimum score is 0 and the maximum is 5. The minimum score is 0 and the maximum is 45. Lower scores indicate better quality of life.
Timepoint [7] 0 0
Day 4
Secondary outcome [8] 0 0
Cost effectiveness - cost-effectiveness ratio of all resources at 12 months - The incremental cost-effectiveness ratio will be determined for both arms of the trial. This is a summary measure representing the economic value of the intervention (oral cefalexin), compared with the alternative (IV cefazolin followed by oral cefalexin). Estimated total sum of all hospital and patient/family resources required per patient per treatment course (AUD) collected by the study team at each study visit using a standard questionnaire (e.g. clinical services, medication, hospital and family accommodation, travelling, loss of income, care arrangements for family members). The mean total cost per treatment cost (AUD) will be reported for each arm of the trial.
Timepoint [8] 0 0
12 months
Secondary outcome [9] 0 0
Treatment adherence - medication reconciliation at 3 weeks - Mean percentage of cefalexin doses taken determined by medication reconciliation (ie. return of any remaining cefalexin) at end of treatment (3 weeks) assessed by the study team/trial pharmacist
Timepoint [9] 0 0
Week 3
Secondary outcome [10] 0 0
Treatment adherence - Morisky Medication Adherence Scale (MMAS) at 3 weeks - Mean Morisky Medication Adherence Scale (MMAS) score. This includes 8 questions and is scored from a minimum of 0 to a maximum of 8. The higher the score, the more likely the respondents were adherent to treatment.
Timepoint [10] 0 0
Week 3

Eligibility
Key inclusion criteria
- Children aged 1 to 18 years with acute, uncomplicated, community-acquired bone and
joint infection who fulfil pre-defined clinical criteria.
Minimum age
1 Year
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Infection due to bacteria resistant to cefalexin or atypical infection (e.g.
mycobacterial, fungal)

2. Features of sepsis as defined by the presence of organ dysfunction (defined using
definitions within the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score)

3. Concomitant severe, invasive infection e.g. necrosing fasciitis

4. Complicated infection (e.g. presence of prosthetic material; subperiosteal or soft
tissue abscess without surgical intervention; infection secondary to or complicated by
trauma)

5. History of allergy to cephalosporin antibiotics or immediate, severe reaction to
penicillins

6. Received more than one IV or oral dose of an antibiotic with activity against the
likely bacteria causing the current infection

7. Prior episode of OM or SA

8. Prior condition predisposing to poor absorption (e.g. inflammatory bowel disease,
current gastrointestinal symptoms) or complicated disease (e.g. immunodeficiency)

9. Prior enrolment in the trial

10. Current recipient of another investigational product as part of a clinical trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Royal Children's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3051 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a single centre trial of children with bone and joint infections (BJIs). 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 2 to 4 days
followed by an oral antibiotic course in achieving full recovery 12 months after
presentation. Children will be randomly allocated to the 'entirely oral antibiotic' group or
the 'standard treatment' group.
Trial website
https://clinicaltrials.gov/show/NCT04538053
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Amanda Gwee, PhD
Address 0 0
Murdoch Childrens Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Alison Boast, MD
Address 0 0
Country 0 0
Phone 0 0
+61393455522
Fax 0 0
Email 0 0
alison.boast@gmail.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04538053