Back to resultsOral-only Antibiotics for Bone and Joint Infections in Children (CHILD@HOME_BJI)
Primary Purpose
Osteomyelitis, Septic Arthritis, Bone Infection
Status
Active
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Oral co-amoxiclav or oral dicloxacillin only
IV ceftriaxon followed by oral co-amoxiclav or oral dicloxacillin
Sponsored by
About this trial
This is an interventional treatment trial for Osteomyelitis
Eligibility Criteria
Inclusion Criteria:
- Children aged 3 months to 18 years with antibiotic treatment of uncomplicated bone or joint infection.
Exclusion Criteria:
- Severe disease, e.g. septic shock, or any concomitant infection, e.g. necrotizing fasciitis, requiring IV antibiotics in the opinion of the treating clinician.
- Complicated bone or joint infection, e.g. prosthetic material, infection secondary to or complicated by trauma, severe pyomyositis or other substantial soft tissue infections.
- 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.
- Significant co-morbidities that might influence the choice of treatment or the course of the infection, e.g. immunodeficiency, immunosuppressive therapy, sickle cell anemia.
- Previous bone or joint infection.
- Antibiotic therapy for more than 24 hours before inclusion.
- Documented pathogen with limited treatment options that do not permit randomization, e.g. the pathogen is only sensitive to intravenous antibiotics.
- Prior enrolment in the trial
Sites / Locations
- Copenhagen University Hospital, Rigshospitalet
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Experimental
Standard
Arm Description
< 5 years: High-dose oral co-amoxiclav (1:8) 33 mg amoxicillin/kg/dose (max. 1 g) three-times daily (TDS) until clinical and paraclinical improvement (min. 3 days) followed by oral co-amoxiclav (1:4) 17 mg amoxicillin/kg/dose (max. 500 mg) TDS for 7 days (arthritis) or 21 days (osteomyelitis). =/> 5 years: High-dose oral dicloxacillin 50 mg/kg/dose (max. 2 g) four-times daily (QID) until clinical and paraclinical improvement (min. 3 days) followed by oral dicloxacillin 25 mg/kg/dose (max. 1 g) QID for 7 days (arthritis) or 21 days (osteomyelitis). Treatment will be adjusted according to microbiological findings.
IV ceftriaxon 100 mg/kg/dose (max. 4 g) once daily (QD) (all ages) until clinical and paraclinical improvement (min. 3 days) followed by: < 5 years: Oral co-amoxiclav (1:4) 17 mg amoxicillin/kg/dose (max. 500 mg) TDS for 7 days (arthritis) or 21 days (osteomyelitis). >/= 5 years: Oral dicloxacillin 25 mg/kg/dose (max. 1 g) QID for 7 days (arthritis) or 21 days (osteomyelitis). Treatment will be adjusted according to microbiological findings.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Recurrent infection
Proportion of children with recurrence of symptoms and signs (same anatomical location) after completion of antibiotic treatment requiring further antibiotic administration
Full Information
NCT ID
NCT04563325
First Posted
September 13, 2020
Last Updated
September 26, 2023
Sponsor
Rigshospitalet, Denmark
Collaborators
The research foundation of Copenhagen University Hospital, Rigshospitalet, Copenhagen Health Science Partners, Innovation Fund Denmark
1. Study Identification
Unique Protocol Identification Number
NCT04563325
Brief Title
Oral-only Antibiotics for Bone and Joint Infections in Children
Acronym
CHILD@HOME_BJI
Official Title
Oral-only Antibiotics for Bone and Joint Infections in Children - A Nationwide Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 15, 2020 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
September 15, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rigshospitalet, Denmark
Collaborators
The research foundation of Copenhagen University Hospital, Rigshospitalet, Copenhagen Health Science Partners, Innovation Fund Denmark
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteomyelitis, Septic Arthritis, Bone Infection, Joint Infection, Bone and Joint Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
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.
Allocation
Randomized
Enrollment
180 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental
Arm Type
Active Comparator
Arm Description
< 5 years: High-dose oral co-amoxiclav (1:8) 33 mg amoxicillin/kg/dose (max. 1 g) three-times daily (TDS) until clinical and paraclinical improvement (min. 3 days) followed by oral co-amoxiclav (1:4) 17 mg amoxicillin/kg/dose (max. 500 mg) TDS for 7 days (arthritis) or 21 days (osteomyelitis).
=/> 5 years: High-dose oral dicloxacillin 50 mg/kg/dose (max. 2 g) four-times daily (QID) until clinical and paraclinical improvement (min. 3 days) followed by oral dicloxacillin 25 mg/kg/dose (max. 1 g) QID for 7 days (arthritis) or 21 days (osteomyelitis).
Treatment will be adjusted according to microbiological findings.
Arm Title
Standard
Arm Type
Active Comparator
Arm Description
IV ceftriaxon 100 mg/kg/dose (max. 4 g) once daily (QD) (all ages) until clinical and paraclinical improvement (min. 3 days) followed by:
< 5 years: Oral co-amoxiclav (1:4) 17 mg amoxicillin/kg/dose (max. 500 mg) TDS for 7 days (arthritis) or 21 days (osteomyelitis).
>/= 5 years: Oral dicloxacillin 25 mg/kg/dose (max. 1 g) QID for 7 days (arthritis) or 21 days (osteomyelitis).
Treatment will be adjusted according to microbiological findings.
Intervention Type
Drug
Intervention Name(s)
Oral co-amoxiclav or oral dicloxacillin only
Intervention Description
High dose oral treatment followed by standard dose oral treatment
Intervention Type
Drug
Intervention Name(s)
IV ceftriaxon followed by oral co-amoxiclav or oral dicloxacillin
Intervention Description
IV treatment followed by standard dose oral treatment
Primary Outcome Measure Information:
Title
Sequelae at 6 months
Description
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 Outcome Measure Information:
Title
Non-acute treatment failure.
Description
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
Title
Recurrent infection
Description
Proportion of children with recurrence of symptoms and signs (same anatomical location) after completion of antibiotic treatment requiring further antibiotic administration
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Safety Outcome 1: Severe complications during antibiotic treatment.
Description
Proportion of children with severe complications during antibiotic treatment, e.g. need for intensive care, septic shock, organ failure, pyomyositis, endocarditis, deep venous thrombosis.
Time Frame
28 days
Title
Safety Outcome 2: Surgical intervention
Description
Proportion of children with need for surgical intervention during antibiotic treatment. Diagnostic surgical intervention (diagnostic joint aspiration or diagnostic bone biopsy) excluded.
Time Frame
28 days
Title
Safety Outcome 3: Treatment related adverse events
Description
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).
Time Frame
3 months
Title
Time to apyrexia from initiation of antibiotic treatment
Time Frame
28 days
Title
Mobility and pain
Description
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]
Time Frame
14 days
Title
Total duration of antibiotic therapy
Time Frame
3 months
Title
Sequelae at 12 months
Description
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.
Time Frame
12 months
Title
Radiological abnormalities at 12 months
Description
Proportion of children with radiological abnormalities assessed by a qualified radiologist 12 months after the initiation of treatment.
Time Frame
12 months
Title
Secondary infection
Description
Proportion of children with secondary infection with antimicrobial-resistant organisms or Clostridium difficile
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Children aged 3 months to 18 years with antibiotic treatment of uncomplicated bone or joint infection.
Exclusion Criteria:
Severe disease, e.g. septic shock, or any concomitant infection, e.g. necrotizing fasciitis, requiring IV antibiotics in the opinion of the treating clinician.
Complicated bone or joint infection, e.g. prosthetic material, infection secondary to or complicated by trauma, severe pyomyositis or other substantial soft tissue infections.
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.
Significant co-morbidities that might influence the choice of treatment or the course of the infection, e.g. immunodeficiency, immunosuppressive therapy, sickle cell anemia.
Previous bone or joint infection.
Antibiotic therapy for more than 24 hours before inclusion.
Documented pathogen with limited treatment options that do not permit randomization, e.g. the pathogen is only sensitive to intravenous antibiotics.
Prior enrolment in the trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allan Bybeck Nielsen, MD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ulrikka Nygaard, Ass Prof PhD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Study Chair
Facility Information:
Facility Name
Copenhagen University Hospital, Rigshospitalet
City
Copenhagen
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Study protocol and statistical analysis plan will be shared. The exact plan for sharing Individual Participant Data (IPD) is being prepared.
Learn more about this trial
Oral-only Antibiotics for Bone and Joint Infections in Children
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