Clinical trial NCT03716921: Short 3-week Antibiotic Treatment Versus 6 Weeks in Adults With Septic Arthritis of Native Joint
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Septic Arthritis
Keywords: Septic Arthritis of native joint
short antibiotic treatment
native joint
septic arthritis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-10-23
Enrollment: 332
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Cure at 16 weeks (4 months) after the beginning of the treatment
timeFrame: 16 weeks after Day 0
Secondary outcomes:
measure: Cure at 24 weeks
timeFrame: 24 weeks after Day 0
measure: Treatment failure and relapse and relapse rates
timeFrame: 6,16,24 weeks after Day 0
measure: The patient's quality of life
timeFrame: 3,6,16,24 weeks after Day 0
measure: The residual joint pain in the affected joint
timeFrame: at 16 and 24 weeks after Day 0
measure: hospital length of stay and total treatments costs
timeFrame: through study completion, an average of 3 years
measure: joint mobility
timeFrame: at 16 and 24 weeks after Day 0
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpital Avicenne - Service de Rhumatologie
city: Bordeaux
country: France
facility: Hôpital Pellegrin Bordeaux - Service de Rhumatologie
city: Boulogne-Billancourt
country: France
facility: Hôpital Ambroise Paré - Service de Rhumatologie
city: Brest
country: France
facility: Hôpital Cavale Blanche - Service de Maladies Infectieuses
city: Cergy-Pontoise
country: France
facility: CHG Pontoise - Centre Hospitalier René Dubos - Service de Rhumatologie
city: Chambray-lès-Tours
country: France
facility: CHU Tours - Hôpital Trousseau - Service de Rhumatologie
city: Clamart
country: France
facility: Hôpital Antoine Béclère - Service de Maladies Infectieuses
city: Corbeil-Essonnes
country: France
facility: CHSF - Service de Rhumatologie
city: Dijon
country: France
facility: CHU Dijon Bourgogne - Hôpital François Mitterrand -Service de Maladies Infectieuses
city: Garches
country: France
facility: Hôpital Raymond Poincaré - Service de Maladies Infectieuses
city: La Tronche
country: France
facility: CHU Grenoble Alpes - Hôpital Michallon - Service de Maladies Infectieuses
city: Le Kremlin-Bicêtre
country: France
facility: Hopital Bicêtre, Service de Maladies Infectieuses et Tropicales
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre service de rhumatologie
city: Lille
country: France
facility: CHRU Lille - Service de Rhumatologie
city: Orléans
country: France
facility: CHR Orléans - Service de Rhumatologie
city: Paris
country: France
facility: Hôpital Lariboisière Service de Rhumatologie
city: Paris
country: France
facility: Hôpital Saint Antoine - Service de Rhumatologie
city: Paris
country: France
facility: Hôpital Pitié Salpetrière - Service de Maladies Infectieuses
city: Paris
country: France
facility: Hôpital Pitié Salpetrière - Service de Rhumatologie
city: Paris
country: France
facility: Hôpital Cochin - Service de Maladies Infectieuses
city: Paris
country: France
facility: Hôpital Cochin - Service de Rhumatologie
city: Paris
country: France
facility: Hôpital Bichat - Service de Rhumatologie
city: Paris
country: France
facility: GH Diaconesse La Croix St Simon - Service de Rhumatologie
city: Rennes
country: France
facility: Hôpital Sud Rennes - Service de Rhumatologie
city: Saint-Priest-en-Jarez
country: France
facility: CHU Saint Etienne - Hôpital Nord - Service de Maladies Infectieuses
city: Saint-Priest-en-Jarez
country: France
facility: CHU Saint Etienne - Hôpital Nord - Service de Rhumatologie
city: Strasbourg
country: France
facility: CHRU Strasbourg - Hôpital de Hautepierre - Service de Rhumatologie
city: Tours
country: France
facility: CHU Tours - Hôpital Bretonneau - Service de Maladies Infectieuses
city: Vandœuvre-lès-Nancy
country: France
facility: Hôpitaux de Brabois - Service de Maladies Infectieuses
city: Vandœuvre-lès-Nancy
country: France
facility: Hôpitaux de Brabois - Service de Rhumatologie
city: Échirolles
country: France
facility: CHU Grenoble Alpes - Hôpital Sud - Service de Rhumatologie
Study officials:
affiliation: AP-HP Hôpital Bicêtre
name: Lélia ESCAUT, Dr
role: PRINCIPAL_INVESTIGATOR
References: