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. (POOMA)

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.

Study Overview

• Status: Recruiting
• Conditions: Osteomyelitis
• Intervention / Treatment: Other: therapeutic strategy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 320
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mathie LORROT, MD PhD; Phone Number: +331 44 73 62 20; Email: mathie.lorrot@aphp.fr
• Study Contact Backup: Name: Franck FITOUSSI, MD PhD; Phone Number: +331 44 73 68 51; Email: franck.fitoussi@aphp.fr

Study Locations

• France
  • Paris, France, 75012
    • Recruiting
    • Trousseau Hospital
    • Contact: Mathie LORROT, MD PhD; Phone Number: +331 44 73 62 20; Email: mathie.lorrot@aphp.fr
    • Principal Investigator: Mathie LORROT, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Other: 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
Experimental: oral antibiotic treatment; Oral antibiotic treatment started in hospital then continued at home for a total duration of 3 weeks of antibiotic therapy	Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete recovery without relapse at 6 months	Complete recovery without relapse defined by the absence of clinical signs of osteomyelitis (absence of pain, fever, swelling & heat of any limb, biological inflammatory signs, relapse or hospitalisation AND the absence of secondary septic complications (septic arthritis, sub-periosteal abscess)	6 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Mathie LORROT, MD PhD, APHP

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2021
• Primary Completion (Anticipated): November 30, 2024
• Study Completion (Anticipated): May 31, 2025

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 18, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Infectious; Osteomyelitis
• Other Study ID Numbers: APHP180672; 2019-003522-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No