Initial Oral Antibiotics for Bone and Joint Infections in Children

NCT ID: NCT06827496

Last Updated: 2025-04-09

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-11-15
• Study Completion Date: 2027-05-31

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.

Conditions

Osteomyelitis Acute; Septic Arthritis; Bone Infection; Joint Infection; Bone and Joint Infection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Children and adolescents with bone and joint infections treated with initial oral antibiotics

Patients 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

Oral antibiotic treatment

Intervention Type: DRUG

Initial antibiotics:

Below 5 years: High-dose amoxicillin-clavulanate (8:1 ratio; 100/12.5 mg/kg/day in 3 doses) until clinical improvement and decrease in CRP, followed by dose reduction (4:1 ratio) to 50/12.5 mg/kg/day in 3 doses).

5 years and above: High-dose anti-staphylococcal penicillin (200 mg/kg/day in 4 doses) until clinical improvement and decrease in CRP, with dose reduction (100 mg/kg/day in 4 doses) after clinical improvement

Treatment duration of follow-up therapy (after initial high-dose antibiotics): One week for uncomplicated joint infections, three weeks for bone infections, and four weeks for spondylodiscitis

Interventions

Oral antibiotic treatment

Initial antibiotics:

Below 5 years: High-dose amoxicillin-clavulanate (8:1 ratio; 100/12.5 mg/kg/day in 3 doses) until clinical improvement and decrease in CRP, followed by dose reduction (4:1 ratio) to 50/12.5 mg/kg/day in 3 doses).

5 years and above: High-dose anti-staphylococcal penicillin (200 mg/kg/day in 4 doses) until clinical improvement and decrease in CRP, with dose reduction (100 mg/kg/day in 4 doses) after clinical improvement

Treatment duration of follow-up therapy (after initial high-dose antibiotics): One week for uncomplicated joint infections, three weeks for bone infections, and four weeks for spondylodiscitis

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innovation Fund Denmark

INDIV

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Ulrikka Nygaard

Ass Professor, Consultant, PhD, MD, MPhil

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ulrikka Nygaard, Ass Professor, PhD, MD, MPhil

Role: STUDY_CHAIR

Copenhagen University Hospital, Rigshospitalet, Denmark

Locations

Rigshospitalet

Copenhagen Ø, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Ulrikka Nygaard, Ass Professor, PhD, MD, MPhil

Role: CONTACT

Ulrikka.Nygaard@regionh.dk

+45 35459761

References

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.

Reference Type: BACKGROUND

PMID: 37263683 (View on PubMed)

Other Identifiers

0176-00020B

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

P-2029-29

Identifier Type: -

Identifier Source: org_study_id