BonE and Joint Infections - Simplifying Treatment in Children Trial (BEST)

Murdoch Childrens Research Institute

Status and phase: Enrolling; Phase 4

Conditions: Bone and Joint Infection; Septic Arthritis; Osteomyelitis; Bone Infection

Treatments: Drug: Oral cefalexin only; Drug: IV cefazolin or IV flucloxacillin followed by oral cefalexin

Study type: Interventional

Funder types: Other

Identifiers

NCT04538053

2019.287

Details and patient eligibility

About

This is a multi- centre trial of children with bone and joint infections (BJIs) at eight major paediatric hospitals in Australia and New Zealand. 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.

Full 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 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.

Enrollment: 285 estimated patients

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children aged 1 to 18 years with acute, uncomplicated, community-acquired bone and joint infection who fulfil pre-defined clinical criteria.

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; large subperiosteal (>3mm) 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 three 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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285 participants in 2 patient groups

Intervention

Active Comparator group

Description:

Children will receive high-dose oral cefalexin 37.5 mg/kg/dose (max 1.5 g) QID 1 to 7 days followed by oral cefalexin 45 mg/kg/dose (max 1.5 g) TDS for a total course of 3 weeks

Treatment:

Drug: Oral cefalexin only

Standard Therapy

Active Comparator group

Description:

Children will receive IV cefazolin 50 mg/kg/dose (max 2 g) three-times daily (TDS) or IV flucloxacillin 50 mg/kg/dise (max 2 g) four-times daily (QID) for 1 to 7 days followed by oral cefalexin 45 mg/kg/dose (max 1.5 g) three-times daily (TDS) for a total course of 3 weeks

Treatment:

Drug: IV cefazolin or IV flucloxacillin followed by oral cefalexin