Septic Arthritis
Conditions
Keywords
Articular prognosis, Corticosteroid, Acute septic arthritis, Antibiotic therapy
Brief summary
Septic arthritis is a severe infection associated with significant morbidity and mortality. Despite eradication of the microorganisms, persistent inflammation may lead to substantial long-term functional joint sequelae. The use of corticosteroids could reduce this inflammation, thereby improving functional joint outcomes and facilitating first-line medical treatment. The hypothesis of this study is that corticosteroid administration, in addition to antibiotic therapy, reduces persistent inflammation and improves functional joint prognosis in adult patients with acute septic arthritis.
Detailed description
Septic arthritis is a severe infection with a mortality rate of 10-15% and morbidity up to 25% due to rapid joint destruction. Despite antibiotic treatment, persistent intra-articular inflammation increases the risk of long-term joint damage. Standard care includes antibiotics and joint drainage, either surgically (arthrotomy or arthroscopy) or by repeated bedside aspiration. Surgery carries risks of nosocomial infections and complications, and aspirations are not always feasible. Corticosteroids are currently not recommended in adult septic arthritis due to concerns that their anti-inflammatory effects might worsen infection. However, corticosteroids have shown benefits in other infections, improving outcomes in meningitis and pneumonia. Animal studies suggest that host inflammatory responses, particularly activation of CD4+ lymphocytes and macrophages, drive joint damage, and corticosteroids reduce this inflammation, preserving cartilage. In children with septic arthritis, corticosteroids have been shown to reduce long-term joint damage, symptom duration, and hospital stay without increasing infection risk. To date, no randomized controlled trials have evaluated corticosteroids in adult septic arthritis. This study aims to assess the efficacy and safety of adjunctive corticosteroid therapy with antibiotics in adults with septic arthritis, focusing on reducing joint sequelae, pain, hospital stay, and surgical interventions.
Interventions
DRUGoral prednisone or placebo at a dose of 60 mg per day for 7 days
oral prednisone or placebo at a dose of 60 mg per day for 7 days
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Experimental arm: Standard antibiotic therapy combined with oral prednisone at a dose of 60 mg per day for 7 days Control arm: Standard antibiotic therapy combined with an oral placebo matching prednisone for 7 days.
Intervention model description
Exploratory phase II therapeutic trial, multicenter, national, controlled and randomized with a 1:1 allocation ratio, double-blind.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Documented septic arthritis (microorganism identified intra-articularly by culture or PCR, or by turbid synovial fluid with positive Gram stain, or positive blood cultures) * Effective antibiotic therapy initiated within ≤ 3 days * Effective contraception for women of childbearing age during treatment period * Signed informed consent * Affiliation to the French national health insurance system * Ability to read, write, and understand French
Exclusion criteria
* Polyarticular septic arthritis (≥ 2 joints) * Septic arthritis of small joints (e.g., fingers: proximal interphalangeal joint (PIP), distal interphalangeal joints (DIP), MetaCarpoPhalangeal (MCP); toes: MTP) * Systemic sclerosis * Pyomyositis * Diabetic foot infection * Current corticosteroid therapy for another indication * Inability to take oral medication * Contraindication to corticosteroids * Associated endocarditis * Presence of prosthetic joint or osteosynthesis material in the affected joint * Septic shock * Severe soft tissue wound overlying the joint * Aplastic chemotherapy * Neutropenia (defined as neutrophils \< 500/mm³) * Mycobacterial infection * Fungal infection * Sickle cell disease * Current pregnancy * Breastfeeding women * Patients under legal protection (e.g., guardianship) * Participation in another interventional clinical trial * Uncontrolled diabetes * Unstable psychiatric disorders * Adults unable to provide informed consent * Contraindication to corticosteroid therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the effect of adjunctive corticosteroid therapy added to standard antibiotic treatment on functional joint outcomes at 24 weeks in adult patients with acute septic arthritis. | 24 weeks | This outcome will be assessed using the total WOMAC score (Western Ontario and McMaster Universities Osteoarthritis Index) for lower limb involvement (hip, knee, or ankle joints). Scores range from 0 to 96 for the total WOMAC where 0 represents the best health status and 96 the worst possible status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effect of corticosteroids on joint range of motion. | 1, 6, and 24 weeks | Joint flexion and extension measured at weeks 1, 6, and 24 using a goniometer. Presence of flexion contracture (defined as incomplete extension) at 3 months, assessed only for septic arthritis of the hip and knee. |
| To assess joint-related complications. | 24 weeks | Any complication assessed by radiological examination of the joint at week 24. |
| To determine whether corticosteroid administration affects the need for surgical intervention. | 24 weeks | Number of surgical interventions between randomization and week 24. |
| To evaluate whether corticosteroids modify the duration of antibiotic therapy. | 24 weeks | Duration of antibiotic therapy. |
| To assess the impact of corticosteroids on length of hospital stay. | 24 weeks | Length of hospital stay |
| To evaluate the effect of corticosteroids on pain. | 24 weeks | Pain assessed by Visual Analog Scale (VAS) at weeks 1, 6, and 24. range of scores from 0-10. A higher score indicates greater pain intensity |
| To assess the effect of corticosteroids on overall mortality. | 24 weeks | Overall mortality. |
| To evaluate the impact of corticosteroids on systemic inflammation. | 24 weeks | Biological inflammatory markers measured at weeks 1, 6, and 24. |
| To assess the effect of corticosteroids on patient-reported recovery. | 24 weeks | Patient self-assessment of recovery on a 0 to 5 scale (0 = no improvement, 5 = full recovery) at weeks 1, 6, and 24. |
| To evaluate the impact of corticosteroids on quality of life. | 24 weeks | Quality of life assessed by the EQ-5D-5L questionnaire at week 24. |
| To assess corticosteroid tolerance, including glycemic control and neuropsychiatric effects. | 24 weeks | All adverse effects and side effects, particularly glycemic control and neuropsychiatric effects, monitored through patient self-surveillance. |
Countries
France
Contacts
CONTACTBenjamin ROSSI, PhD
Outcome results
None listed