BonE and Joint Infections - Simplifying Treatment in Children Trial

Browse trials for

• Arthritis, Infectious 51
• Osteomyelitis 105

Arthritis, Infectious

51 studies on the registry are indexed under Arthritis, Infectious; 12 are open to participants now.

This study's planned enrollment of 214 is above the median of 41 across 21 interventional studies indexed under Arthritis, Infectious.

Lead sponsor

Murdoch Childrens Research Institute is the lead sponsor of 99 studies on the registry; 34 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 3 (60%) have results posted.

Study arms

• Active comparator
  Intervention

  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

  Drug: Oral cefalexin only

• Active comparator
  Standard Therapy

  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

  Drug: IV cefazolin or IV flucloxacillin followed by oral cefalexin

Interventions

• DrugOral cefalexin only

  High-dose oral cefalexin

• DrugIV cefazolin or IV flucloxacillin followed by oral cefalexin

  Standard therapy of IV cefazolin or IV flucloxacillin followed by high dose oral cefalexin

Primary outcomes

1. 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.

   Time frame: 3 months

Secondary outcomes

1. 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.

   Time frame: 6 months

2. 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.

   Time frame: 12 months

3. 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

   Time frame: 3 months

4. 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.

   Time frame: 12 months

5. 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)

   Time frame: Between Day 1-7

6. 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.

   Time frame: 3 months

7. 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.

   Time frame: Day 8 through to Day 14 (once), and 12 months

8. 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.

   Time frame: Once between Day 8 to Day 14

9. 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.

   Time frame: Day 8 through Day 14 (once) and 3 months

10. 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.

    Time frame: Between Week 2 to 4

11. 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.

    Time frame: 12 months

Individual participant data

Plan to share: 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

Supporting information: Study protocol, Statistical analysis plan, Clinical study report, Analytic code

Time frame: Time Frame: 6 months after publication of primary outcome

Access criteria: Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the BEST Trial Principle and Associate Investigators must see and approve the analysis plan describing how the data will be analysed, there must be an agreement around appropriate acknowledgement and any additional costs involved must be covered. Data will only be shared with a recognised research institution which has approved the proposed analysis plan.

Data sharing details ↗ · www.mcri.edu.au