Clinical trial NCT06827496: Initial Oral Antibiotics for Bone and Joint Infections in Children
Official title: Initial Oral Antibiotics for Bone and Joint Infections in Children: A Prospective Nationwide Real-world Effectiveness Study in Denmark
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Osteomyelitis Acute
Septic Arthritis
Bone Infection
Joint Infection
Bone and Joint Infection
Keywords: Bone and joint infections
Children
Oral antibiotics
Osteomyelitis
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Innovation Fund Denmark
First posted: 2025-02-14
Enrollment: 100
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children aged 3 months to 17 years with uncomplicated bone and joint infections treated with initial oral antibioticsbetween 15th of November 2024 and 15th of November 2026

Brief summary: Initial oral antibiotic treatment for children and adolescents with uncomplicated bone and joint infections (BJI) has been found non-inferior to initial IV antibiotics in one randomized controlled trial (RCT). The real-world effectiveness of initial oral antibiotics for children and adolescents with BJI is unclear.

This nationwide, prospective, multicenter, real-world cohort study aims to compare the effectiveness and safety of initial oral antibiotic treatment for children and adolescents with uncomplicated BJI in a real-world setting with those who received initial oral antibiotics in our RCT.

Detailed description: Background:

Initial oral antibiotic treatment for children and adolescents with uncomplicated BJI has been found non-inferior to initial IV antibiotics in one randomized controlled trial (RCT) from Denmark. The real-world effectiveness of initial oral antibiotics for children and adolescents with BJI is unclear. In Denmark, initial oral antibiotics were allowed in nationwide guidelines for children and adolescents aged 3 months to 17 years with uncomplicated BJI from 2024.

Aim:

We aim to compare the effectiveness and safety of initial oral antibiotics for children and adolescents with uncomplicated BJI in a real-world setting with those who received initial oral antibiotics in our RCT.

Study design:

Nationwide, prospective, multicenter, real-world cohort study.

Patients:

100 children and adolescents aged 3 months to 17 years with uncomplicated BJI treated with initial oral antibiotics at one of the 18 Pediatric Departments in Denmark from 2024 to 2026. Uncomplicated BJI is defined by the absence of impaired general condition or signs of sepsis, rapidly progressing or severe symptoms, pronounced soft tissue involvement, prosthetic material, resistant pathogens, and severe comorbidities. Patients who have received intravenous antibiotic therapy for less than 24 h before oral antibiotics will be included.

Control patients are 98 patients who received initial oral antibiotics for uncomplicated BJI as part of a Danish RCT conducted between 2020 and 2023.

Methods:

All children and adolescents treated for BJI will be prospectively enrolled. Designated co-investigators in the 18 Danish pediatric departments will ensure prospective, national inclusion. Follow-up assessments will be conducted after three, six, 12 month. The three-month follow-up will include a clinical examination to ensure full recovery. The six and 12-month follow-up will be conducted via a structured telephone interview and/or a clinical evaluation.

All study data will be securely collected and managed in an online database.

Outcomes:

The primary outcome is sequelae after 6 months, defined as any atypical mobility or function of the affected bone or joint.

Secondary outcomes are suspicion of treatment failure within 28 days, full recovery after initiation of treatment, recurrent infection within 6 months, and sequelae after 12 months and 5 years.

Safety outcomes are surgical intervention and severe complications during antibiotic treatment.

We will calculate the risk difference sequelae between the real-world and RCT cohorts using exact unconditional two-sided 95% confidence interval.

Eligibility criteria: Children and adolescents aged 3 months to 17 years with uncomplicated bone and joint infections treated with initial oral antibiotics.

According to Danish Nationwide Guidelines (initiated in 2024), initial oral antibiotics are recommended to patients with no risk factors for complicated disease. Risk factors include for complicated disease include:

1. Severe illness or sepsis
2. Rapid symptom progression
3. Pronounced symptoms, including severe pain
4. Pronounced soft tissue involvement
5. Foreign material or post-surgical infection
6. Infection with a resistent or rare pathogen, e.g., Salmonella or MRSA
7. Severe comorbidity, including immunodeficiency

Patients who have received intravenous antibiotic therapy for less than 24 h before oral antibiotics will be included

Primary outcomes:
measure: Clinical sequelae at 6 months
timeFrame: 6 months after end of treatment [4-9 months]
Secondary outcomes:
measure: Suspicion of treatment failure within 28 days
timeFrame: 28 days after initiation of treatment
measure: Full recovery after initiation of treatment
timeFrame: Within 3 months after initiation of treatment (0-4 months)
measure: Recurrent infection within 6 months
timeFrame: 6 months after the end of treatment
measure: Clinical sequelae at 12 months
timeFrame: 12 months after the end of treatment [9-16 months]
measure: Sequelae at 5 years
timeFrame: 5 years after the end of treatment [4-6 years]
Other outcomes:
measure: Safety outcome 1: Surgical intervention
timeFrame: 28 days after initiation of treatment
measure: Safety outcome 2: Severe complications during antibiotic treatment
timeFrame: 28 days after initiation of treatment
Locations:
city: Copenhagen Ø
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: Copenhagen University Hospital, Rigshospitalet, Denmark
name: Ulrikka Nygaard, Ass Professor, PhD, MD, MPhil
role: STUDY_CHAIR
References:
citation: Bybeck Nielsen A, Borch L, Damkjaer M, Glenthoj JP, Hartling U, Hoffmann TU, Holm M, Helleskov Rasmussen A, Schmidt LS, Schmiegelow K, Stensballe LG, Nygaard U; Local Investigators. Oral-only antibiotics for bone and joint infections in children: study protocol for a nationwide randomised open-label non-inferiority trial. BMJ Open. 2023 Jun 1;13(6):e072622. doi: 10.1136/bmjopen-2023-072622.