Oral-only Antibiotics for Bone and Joint Infections in Children

NCT04563325 | Completed Phase 4 DMC

• 1 other identifier: H-20009117
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (2)

• Non-acute treatment failure.

  28 days

• Recurrent infection

  6 months

Other Outcomes (9)

• Safety Outcome 1: Severe complications during antibiotic treatment.

  28 days

• Safety Outcome 2: Surgical intervention

  28 days

• Safety Outcome 3: Treatment related adverse events

  3 months

Study Arms (2)

Experimental

ACTIVE COMPARATOR

\< 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.

Drug: Oral co-amoxiclav or oral dicloxacillin only

Standard

ACTIVE COMPARATOR

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.

Drug: IV ceftriaxon followed by oral co-amoxiclav or oral dicloxacillin

Interventions

Oral co-amoxiclav or oral dicloxacillin only DRUG

High dose oral treatment followed by standard dose oral treatment

Experimental

IV ceftriaxon followed by oral co-amoxiclav or oral dicloxacillin DRUG

IV treatment followed by standard dose oral treatment

Standard

Eligibility Criteria

• Age: 3 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 3 months to 18 years with antibiotic treatment of uncomplicated bone or joint infection.

You may not qualify if:

• 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.
• 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.
• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• The research foundation of Copenhagen University Hospital, Rigshospitalet: collaborator
• Copenhagen Health Science Partners: collaborator
• Innovation Fund Denmark: collaborator

Study Sites (1)

Copenhagen University Hospital, Rigshospitalet

Copenhagen, Denmark

Location

Related Publications (2)

• Nielsen AB, Holm M, Lindhard MS, Glenthoj JP, Borch L, Hartling U, Schmidt LS, Rytter MJH, Rasmussen AH, Damkjaer M, Lemvik G, Petersen JJH, Sondergaard MJ, Thaarup J, Kristensen K, Jensen LH, Hansen LH, Lawaetz MC, Gottliebsen M, Horsager TH, Zaharov T, Hoffmann TU, Nygaard T, Justesen US, Stensballe LG, Vissing NH, Blanche P, Schmiegelow K, Nygaard U. Oral versus intravenous empirical antibiotics in children and adolescents with uncomplicated bone and joint infections: a nationwide, randomised, controlled, non-inferiority trial in Denmark. Lancet Child Adolesc Health. 2024 Sep;8(9):625-635. doi: 10.1016/S2352-4642(24)00133-0. Epub 2024 Jul 15.

  PMID: 39025092 DERIVED

• 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.

  PMID: 37263683 DERIVED

MeSH Terms

Conditions

Osteomyelitis; Arthritis, Infectious

Interventions

Amoxicillin-Potassium Clavulanate Combination; Dicloxacillin

Condition Hierarchy (Ancestors)

Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Cloxacillin; Oxacillin

Study Officials

• Allan Bybeck Nielsen, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Ulrikka Nygaard, Ass Prof PhD

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: September 13, 2020
• First Posted: September 24, 2020
• Study Start: September 15, 2020
• Primary Completion: January 1, 2024
• Study Completion: August 5, 2024
• Last Updated: April 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

DK (1)