Clinical trial NCT04554108: 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.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Osteomyelitis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-09-18
Enrollment: 320
Sex: ALL
Minimum age (years): 1
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial of non inferiority, with active control, in open multicenter.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complete recovery without relapse at 6 months
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Trousseau Hospital
Study officials:
affiliation: APHP
name: Mathie LORROT, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: