Short 3-week Antibiotic Treatment Versus 6 Weeks in Adults With Septic Arthritis of Native Joint

Study Overview
=================
Brief Summary
-----------------
In France, the incidence of native joint infections is about 10 per 100 000 person-years, most commonly caused by S.aureus followed by b-haemolytic streptococci. French and international antibiotic guidelines, based on expert advice and retrospective studies, recommend intravenous antibiotics for two weeks, then oral for 4 weeks without evident link between intravenous, prolonged oral treatment and cure. Long term exposure to antibiotics increases bacterial resistance, a major problem of public health. Several studies show that serious infectious can be treated safely by a shorter treatment and with oral antibiotics. There is no randomized controlled trial to establish the duration of antibiotics in native joint infections. Moreover, no consensus prevails on the administration route and duration of antimicrobial therapy. Although most clinicians acknowledge the interest of oral antibiotics and shorter treatment duration, randomized controlled trials are necessary to evaluate this practice. The SHASAR project aims to evaluate whether a shorter antibiotic treatment (3 week treatment) is safe and not inferior to the conventional 6 week treatment in native joint infections. If successful, this would represent a major advance in terms of patients' quality of life; decreased rate of health-care-related infections and complications, bacterial resistance and cost.

Detailed Description
-----------------
This trial is a nationwide, non inferiority, multicenter French randomized, open-label, controlled trial comparing two treatment durations, 3 versus 6 weeks, in septic arthritis of native joints. Patients who fulfill inclusion criteria will be randomized between day0 and day5. Day 0 is the time when effective intravenous antibiotic treatment is started. Effective treatment is defined by active antibiotics on the identified bacteria according to the susceptibility. The randomisation (1:1 ratio) will be stratified on early planned drainage. Follow-up will include 6 visits and will consist in clinical, biological, radiological, health quality of life (EQ-5D-3L score) and adverse events record. After collection, validation of data and population description, analysis will be conducted on the per-protocol population (patients receiving the planned duration of antibiotic +/-3days). This study will not be carried out blind for feasibility reasons. According to statistical considerations (by accounting for 5% of subjects lost to follow-up), the required sample size will be of 350 patients overall.

Official Title
-----------------
Short 3-week Antibiotic Treatment Versus 6 Weeks in Adults With Septic Arthritis of Native Joint: a Randomized, Open Label, Non-inferiority Trial

Conditions
-----------------
Septic Arthritis

Intervention / Treatment
-----------------
* Other: Short antibiotics treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Septic arthritis of native joint defined by: 1) clinical signs (hot and/or swollen and/or tender and painful joint (measured by a visual analogue scale)) and 2) microbiologically confirmed pyogenic arthritis (microorganism cultured in the synovial fluid joint or in the blood with complete bacterial susceptibility) Patients aged of 18 years or older Informed, written consent obtained from the patient Patient having the rights to French social insurance Exclusion Criteria: Prosthetic joints Septic arthritis in the past 12 months Osteomyelitis Diabetic foot Septic choc Arthritis due to bacteria resistant to available oral antibiotics Arthritis due to the following microorganisms: Mycobacterium, fungi, Brucella, Borrelia, Neisseria gonorrhoeae, Neisseria meningitidis, Nocardia, Mycoplasma spp, Pseudomonas aeruginosa. Glomerular filtration rate < 30ml/min/1,73m2 Neutrophils < 500/mm3 Difficulties regarding compliance with oral antibiotics Contraindication to oral antibiotics necessary to treat joint infection Pregnancy or lactating woman Curator or guardianship Participation in other interventional research during the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Short antibiotics treatment<br>patients will receive effective antibiotic treatment (IV and oral) for 3 weeks | Other: Short antibiotics treatment<br>* Patients randomized in this arm will pursue antibiotic administration until visit 3 weeks after D0<br>* Other names: 3-week antibiotic treatment;|
| No Intervention: Long antibiotics treatment<br>patients will receive effective antibiotic treatment (IV and oral) for 6 weeks according to standard care | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure at 16 weeks (4 months) after the beginning of the treatment | Cure is defined as absence of clinical signs of joint infection, absence of treatment failure, absence of relapse | 16 weeks after Day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure at 24 weeks | Cure is defined as absence of clinical signs of joint infection, absence of treatment failure, absence of relapse | 24 weeks after Day 0 | 
| Treatment failure and relapse and relapse rates | % of relapse at 6,16,24 weeks | 6,16,24 weeks after Day 0 | 
| The patient's quality of life | assessed by a quality of life questionnaire on 3,6,16,24 weeks. The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. | 3,6,16,24 weeks after Day 0 | 
| The residual joint pain in the affected joint | The residual joint pain is measured by a numerical scale. 0 means no pain at all and 10 pain as bad as it could be. | at 16 and 24 weeks after Day 0 | 
| hospital length of stay and total treatments costs | To compare cost-effectiveness and cost utility of 3-week vs 6-week antibiotic strategies for patients with arthritis of native joints | through study completion, an average of 3 years | 
| joint mobility | joint mobility is assessed by good mobility, few mobility, no mobility | at 16 and 24 weeks after Day 0 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Septic Arthritis of native joint, short antibiotic treatment, native joint, septic arthritis