Acute Non-severe Osteomyelitis in Children - Outpatient Management Strategy With Oral Antibiotic Therapy Compared to a Standard Strategy With Conventional Hospitalization and Intravenous Antibiotic Therapy: a Randomized Open-label Non-inferiority Study With Bayesian and Medical-economic Analyses.

NCT ID: NCT04554108

Last Updated: 2021-10-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 320 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-31
• Study Completion Date: 2025-05-31

Brief Summary

The incidence of bone and joint infections (BJI) in children (osteomyelitis, septic arthritis and spondylodiscitis) is 22 per 100,000 children in France. Every year, 3,000 children are hospitalized for BJI, 46% of whom are hospitalized for osteomyelitis. The clinical pictures of BJI are varied: some are severe from the outset; others are non-severe, such as BJIs in Kingella kingae, which are most common in children between the ages of 6 months and 5 years. Currently, the management of children's BJI, regardless of their severity, involves initial hospitalization to start intravenous antibiotic therapy. This non-inferiority trial evaluates, in children with acute osteomyelitis with no severity criteria, less invasive outpatient management with an oral antibiotic treatment given at the outset compared to standard management.

Main objective : Demonstrate the non-inferiority of an ambulatory management strategy versus a standard strategy involving hospitalization on complete recovery without relapse at 6 months after an episode of acute osteomyelitis in children aged 1-4 years without severity criteria.

Primary endpoint: Complete cure without relapse at 6 months defined by the absence of clinical signs of osteomyelitis at 6 months AND the absence of secondary septic complications (septic arthritis, periosteal abscess) before the end of antibiotic therapy AND the absence of relapse or rehospitalization for osteomyelitis related to the initial infection. This criterion will be assessed blindly by an adjudication committee.

Randomized controlled trial of non inferiority, with active control, in open multi-center.

The control or experimental arm allocation (1:1 ratio) will be open-label of the physician, patient and parents. This is a PROBE study: The evaluation of the main judgment criterion will be carried out blindly by an adjudication committee.

Detailed Description

The incidence of bone and joint infections (BJI) in children (osteomyelitis, septic arthritis and spondylodiscitis) is 22 per 100,000 children in France. Every year, 3,000 children are hospitalized for BJI, 46% of whom are hospitalized for osteomyelitis. The clinical pictures of BJI are varied: some are severe from the outset; others are non-severe, such as BJIs in Kingella kingae, which are most common in children between the ages of 6 months and 5 years. Currently, the management of children's BJI, regardless of their severity, involves initial hospitalization to start intravenous antibiotic therapy. This non-inferiority trial evaluates, in children with acute osteomyelitis with no severity criteria, less invasive outpatient management with an oral antibiotic treatment given at the outset compared to standard management.

Main objective : Demonstrate the non-inferiority of an ambulatory management strategy versus a standard strategy involving hospitalization on complete recovery without relapse at 6 months after an episode of acute osteomyelitis in children aged 1-4 years without severity criteria.

Primary endpoint: Complete cure without relapse at 6 months defined by the absence of clinical signs of osteomyelitis at 6 months AND the absence of secondary septic complications (septic arthritis, periosteal abscess) before the end of antibiotic therapy AND the absence of relapse or rehospitalization for osteomyelitis related to the initial infection. This criterion will be assessed blindly by an adjudication committee.

Randomized controlled trial of non inferiority, with active control, in open multi-center.

The control or experimental arm allocation (1:1 ratio) will be open-label of the physician, patient and parents. This is a PROBE study: The evaluation of the main judgment criterion will be carried out blindly by an adjudication committee.

Conditions

Osteomyelitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intravenous antibiotic treatment

Intravenous antibiotic treatment started during an initial hospitalization of 3 days, with continuation of oral antibiotic therapy at home for a total duration of antibiotic therapy of 3 weeks

Group Type: ACTIVE_COMPARATOR

therapeutic strategy

Intervention Type: OTHER

Outpatient management strategy of acute non-severe osteomyelitis in children with oral antibiotic therapy compared to a standard strategy with conventional hospitalization and intravenous antibiotic therapy

oral antibiotic treatment

Oral antibiotic treatment started in hospital then continued at home for a total duration of 3 weeks of antibiotic therapy

Group Type: EXPERIMENTAL

therapeutic strategy

Intervention Type: OTHER

Outpatient management strategy of acute non-severe osteomyelitis in children with oral antibiotic therapy compared to a standard strategy with conventional hospitalization and intravenous antibiotic therapy

Interventions

therapeutic strategy

Outpatient management strategy of acute non-severe osteomyelitis in children with oral antibiotic therapy compared to a standard strategy with conventional hospitalization and intravenous antibiotic therapy

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Child ≥ 1 year and 4 years old ;

• First episode of acute osteomyelitis suspected on clinical grounds (acute functional impotence (<15 days) most often associated with fever) and confirmed in the first days of treatment by bone scan or MRI.
• Absence of severity criteria :

• Fever < 39°C
• AND absence of sepsis (absence of hemodynamic disorders, respiratory disorders, consciousness disorders)
• AND absence of periosteal abscess or associated arthritis or deep vein thrombosis
• AND absence of scarlatiniform rash (no gap of healthy skin)
• AND CRP < 50 mg/ml
• AND normal initial bone radiograph (or simple soft tissue thickening).

Exclusion Criteria

• Multifocal osteoarticular infections
• Sickle cell or immunocompromised patients
• Antibiotic treatment in progress or within 48 hours prior to the emergency room visit
• History of severe beta-lactam allergy (anaphylactic shock, angioedema)
• Digestive problems (vomiting or diarrhea)
• Refusal of parents to participate
• Parents (children) not affiliated to social security or without CMU
• Parents who do not speak French
• Participation in another intervention research protocol

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mathie LORROT, MD PhD

Role: PRINCIPAL_INVESTIGATOR

APHP

Locations

Trousseau Hospital

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Mathie LORROT, MD PhD

Role: CONTACT

mathie.lorrot@aphp.fr

+331 44 73 62 20

Franck FITOUSSI, MD PhD

Role: CONTACT

franck.fitoussi@aphp.fr

+331 44 73 68 51

Facility Contacts

Mathie LORROT, MD PhD

Role: primary

mathie.lorrot@aphp.fr

+331 44 73 62 20

Other Identifiers

2019-003522-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP180672

Identifier Type: -

Identifier Source: org_study_id