Bone and Joint Infection, Bone Infection, Joint Infection, Osteomyelitis, Septic Arthritis
Conditions
Brief summary
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.
Interventions
DRUGIV ceftriaxon followed by oral co-amoxiclav or oral dicloxacillin
IV treatment followed by standard dose oral treatment
DRUGOral co-amoxiclav or oral dicloxacillin only
High dose oral treatment followed by standard dose oral treatment
Sponsors
The research foundation of Copenhagen University Hospital, Rigshospitalet
Copenhagen Health Science Partners
Innovation Fund Denmark
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The assessor (qualified pediatrician or pediatric surgeon) of the primary endpoint (sequelae 6 months after initiation of treatment) will be blinded for the intervention as well as any other details on the course of disease. The assessor will be informed about the age of the child as well as the approximate location of the infection and will perform a predefined systematic clinical examination of the relevant area (categories: 1) lower extremities, 2) upper extremities incl. claviculae and scapulae and 3) columna, costae and sternum). The exact anatomical location including side (left or right) will not be revealed. The child and parents will be followed by a study nurse who will secure that the blinding is respected. The primary endpoint is met if there are any positive findings related to the previously infected bone or joint.
Eligibility
Sex/Gender
ALL
Age
3 Months to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sequelae at 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-acute treatment failure. | 28 days | 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. |
| Recurrent infection | 6 months | Proportion of children with recurrence of symptoms and signs (same anatomical location) after completion of antibiotic treatment requiring further antibiotic administration |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to apyrexia from initiation of antibiotic treatment | 28 days | — |
| Mobility and pain | 14 days | Level of mobility and pain assessed by daily grading of symptoms by medical staff as well as daily standardized pain scores by participants and/or parents. Score systems: Visual Analog Scale (VAS) or Face Legs Activity Cry Consolability (FLACC) scale, both with scores from 0 (no pain) to 10 (worst pain). \[14 days\] |
| Total duration of antibiotic therapy | 3 months | — |
| Safety Outcome 1: Severe complications during antibiotic treatment. | 28 days | Proportion of children with severe complications during antibiotic treatment, e.g. need for intensive care, septic shock, organ failure, pyomyositis, endocarditis, deep venous thrombosis. |
| Radiological abnormalities at 12 months | 12 months | Proportion of children with radiological abnormalities assessed by a qualified radiologist 12 months after the initiation of treatment. |
| Secondary infection | 3 months | Proportion of children with secondary infection with antimicrobial-resistant organisms or Clostridium difficile |
| Sequelae at 12 months | 12 months | Proportion of children with sequelae, e.g. abnormal mobility, growth abnormalities assessed by clinical examination by a qualified pediatrician 12 month after initiation of treatment. |
| Safety Outcome 2: Surgical intervention | 28 days | Proportion of children with need for surgical intervention during antibiotic treatment. Diagnostic surgical intervention (diagnostic joint aspiration or diagnostic bone biopsy) excluded. |
| Safety Outcome 3: Treatment related adverse events | 3 months | Proportion of children with treatment related adverse events e.g. complications of IV access (infection, need for replacement, extravasation) and drug side effects reported by medical staff or by parents (electronic questionnaire). |
Countries
Denmark
Outcome results
None listed