Oral-only Antibiotics for Bone and Joint Infections in Children

Rigshospitalet, Denmark180 enrolled

Overview

A nationwide, multicenter, randomized, non-inferiority trial of children with bone and joint infections. The primary objective is to determine if oral-only antibiotics (experimental arm) is non-inferior to initial intravenous antibiotics followed by oral therapy (control arm). Children will be randomized 1:1. The total treatment duration is identical in both groups. The study is open label with blinding of the primary endpoint assessor.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

180

Conditions

Osteomyelitis Septic Arthritis Bone Infection Joint Infection Bone and Joint Infection

Interventions

Oral co-amoxiclav or oral dicloxacillin onlyDRUG

High dose oral treatment followed by standard dose oral treatment

IV ceftriaxon followed by oral co-amoxiclav or oral dicloxacillinDRUG

IV treatment followed by standard dose oral treatment

Eligibility

Sex: ALLMin age: 3 MonthsMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Children aged 3 months to 18 years with antibiotic treatment of uncomplicated bone or joint infection. Exclusion Criteria: 1. Severe disease, e.g. septic shock, or any concomitant infection, e.g. necrotizing fasciitis, requiring IV antibiotics in the opinion of the treating clinician. 2. Complicated bone or joint infection, e.g. prosthetic material, infection secondary to or complicated by trauma, severe pyomyositis or other substantial soft tissue infections. 3. Expected need of major surgery within the first 24 hours of treatment, e.g. drilling, debridement, fenestration, surgical drainage, synovectomy. Minor surgery as diagnostic surgical bone biopsy or diagnostic joint fluid aspiration including lavage is not a criterion for exclusion. 4. Significant co-morbidities that might influence the choice of treatment or the course of the infection, e.g. immunodeficiency, immunosuppressive therapy, sickle cell anemia. 5. Previous bone or joint infection. 6. Antibiotic therapy for more than 24 hours before inclusion. 7. Documented pathogen with limited treatment options that do not permit randomization, e.g. the pathogen is only sensitive to intravenous antibiotics. 8. Prior enrolment in the trial

Outcomes

Primary Outcomes

Sequelae at 6 months

Proportion of children with sequelae 6 months after initiation of treatment defined as abnormal mobility or function of the affected joint/bone. Evaluated by blinded clinical examination by a qualified pediatrician and/or pediatric orthopedic surgeon.

Time frame: 6 months

Secondary Outcomes

Non-acute treatment failure.

Proportion of children with change of antibiotic therapy due to non-acute treatment failure. This will be evaluated by two pediatric specialists and is suggested by e.g. 1) temperature above 38,5 after more than 72 hours of antibiotic therapy, 2) increasing CRP ( C-reactive protein) after more than 96 hours of antibiotic therapy and 3) no improvement in mobility or pain after 120 hours of antibiotic therapy.

Time frame: 28 days

Recurrent infection

Proportion of children with recurrence of symptoms and signs (same anatomical location) after completion of antibiotic treatment requiring further antibiotic administration